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Drug Delivery - Science topic

Pharmaceutical Drug Delivery
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This question investigates the potential of using specially designed DNA molecules to improve the precision and effectiveness of drug delivery in cancer treatment.
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Pay attention to TDN. A “tetrahedral DNA nanostructure” (TDN) is a 3D nanostructure that possesses a pyramidal shape and is produced by the complementary interaction of four individual DNA strands.The TDN has been suggested to be a potential vehicle for pharmaceuticals because of its exceptional stability, biocompatibility , abundant sites for functional modifications, compatibility with many medications, and outstanding rates of cellular absorption.
Water in human biological cells has a size of 4-6 nm. Therefore, the extensive parameters of the ensemble of small systems of water and other cellular molecules oscillate significantly. Due to the evolution of the cell in the same energy regime, it has the condition ħω ≅ 𝑘T at 36.50C. Therefore, the frequency of quantum oscillations in the double-well potential should be in the terahertz range. The terahertz range of electromagnetic radiation is a promising range for unconventional, and possibly the main treatment of humans in the future. A person exists on the verge of equality of the energies of thermal and quantum fluctuations of water. If the energy of one of these oscillations prevails, a person becomes unstable to infections or gets sick.
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Some of them did the drug release study by Franz diffusion cell . In some other papers people done drug release study by swelling the material into the saline and recording the readings in particular time intervals. But both are completely different environment. Which is correct method to evaluate the drug release for wound healing application.
kindly share your opinion. Thank you
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The saline swelling method is often more representative of wound healing applications, as wounds typically have a moist environment with exudates. This method better simulates the conditions a wound dressing or drug delivery system will encounter in situ, leading to more accurate release profiles for such applications.
The Franz diffusion cell could also be used if the study’s goal is to understand permeation through intact skin. However, for direct wound applications, the saline method aligns more closely with physiological conditions and may provide a more reliable indication of drug release behavior in an actual wound setting.
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I am working on drug delivery systems, Are there any tests, or criteria to evaluate the drug delivery systems
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In case of micro/nano-carriers, there is some sort of a template you can find in almost every publication you read. I will try to list and summarize the ones I am familiar with.
1- Initial Assessments: Size, Stability, and Structure:
We begin with Dynamic Light Scattering (DLS) to evaluate the particle size and uniformity (poly or mono-dispersity). Electrophoretic Light Scattering helps us understand zeta potential, providing insights into the colloidal stability of these carriers and interaction with other systems.
For visual insights, Electron Microscopy offers surface and internal imagery, while Atomic Force Microscopy (AFM) provides a three-dimensional profile at an atomic level, revealing the topography of these carriers.
2- In-Depth Material Characterization:
X-ray Diffraction (XRD) is employed to examine the crystallinity of the encapsulated drug or the carrier system. Raman Spectroscopy and Fourier Transform Infrared Spectroscopy (FTIR) serve to confirm drug presence and study carrier-drug interactions. Differential Scanning Calorimetry (DSC) reveals thermal behaviours, aiding in understanding the physical state of the drug within the carrier.
3- Drug Loading and Stability Checks:
We measure drug loading and encapsulation efficiency to determine how effectively the carrier can contain and deliver the drug, either directly or indirectly using HPLC or UV-Vis spectroscopy.
Pharmaceutical stability assessments look at how these properties hold up over time under various storage conditions and within biological fluids, simulating in vivo conditions.
4- Laboratory and Biological Trials (in-vitro, ex-vivo, and in-vivo):
In-vitro, we simulate drug release kinetics to predict how the carrier will perform in the body. Also, cellular uptake and cytotoxicity studies which assess the interaction between carriers and cells, ensuring safety and efficacy. More in-vitro experiments can be chosen depending on the nature of your drug payload and intended application.
Transitioning to in-vivo studies, pharmacokinetics and biodistribution are tracked in animal models to observe how the drug navigates through the body.
I hope my answer helps you have a detailed picture of how we usually perform characterization tests. The specific criteria for each test depend on the type of carrier you'll use, so it would be better to specify it first, then read about it.
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I saw a lot of research showing the application of DNA as starting material for synthesis of patterned DNA hydrogels or nucleospheres that utilize the self-complementarity of custom designed synthetic oligonucleotides to form such nano and microstructures (1). Another technology exists which uses DNA along with metal ions to form particles through coordination driven self assembly (2). Researchers have also shown the application of such DNA origami structures constructed from custom oligonucleotides and phage DNA in orthotopic tumor-bearing mice models for efficient drug delivery (3).
I am curious to know if we can isolate DNA from other cells (Plants/bacteria/mammalian) and use it to generate such DNA micro or nanoparticles that could have drug delivery applications. What would be the limiting factors in this ?
2. Engineering multifunctional DNA hybrid nanospheres through coordination-driven self-assembly. https://doi.org/10.1002/anie.201810735
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You can isolate DNA from other cells (plants/bacteria/mammals) and use it to create micro- or nanoparticles of DNA that could be used in drug delivery. Limitations:
1. lack of usefulness of such a drug delivery strategy
2. impact of bacterial DNA on human health
3. correct formation of a container of DNA to contain the drug
4. toxicity of oligonucleotides to the human body.
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Please provide a detailed explanation of the process, mechanism, and structural changes involved in water-based gels controlling the release of drugs.
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I am working on a drug delivery, I have to study the nano drug carriers, As of now I am reading from research papers. Are there any databases?, so I can cover all the existing nano drug carriers. It will help me to study them effectively.
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  • How we can use Resolvability parameters in pharmaceutical sciences. Like in drug delivery, or others
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Resolvability parameters in pharmaceutical sciences are used to assess the separation efficiency of different components in a mixture during chromatographic analysis, such as High-Performance Liquid Chromatography (HPLC). These parameters help in optimizing the separation process by ensuring that closely eluting compounds are distinguishable, which is crucial for accurate identification and quantification of pharmaceutical compounds. In practice, resolvability parameters guide adjustments in experimental conditions like solvent composition, flow rate, and column selection to improve the resolution between peaks, thereby enhancing the reliability of the analysis.
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I am currently working on a project involving liposomes and need to determine the maximum volume of siRNA that can be added to a 2.5 mL liposome solution with a total lipid concentration of 10 mg/mL. I need advice on how to calculate or estimate this volume.
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I am not an expert in this field, but I am very interested and have researched to find an answer. I received some assistance from tlooto.com for this response. Could you please review the response below to see if it is correct?
To determine the maximum volume of siRNA that can be added to a 2.5 mL liposome solution with a 10 mg/mL lipid concentration, consider the lipid-to-siRNA weight ratio. Common ratios range from 5:1 to 20:1 [1][2]. With a 10:1 ratio, you have 25 mg of lipids (2.5 mL * 10 mg/mL), allowing for 2.5 mg of siRNA. Given the siRNA concentration, calculate the corresponding volume. For example, if the siRNA is at 1 mg/mL, you can add up to 2.5 mL of siRNA solution. This assumes optimal encapsulation and stability conditions [3][4].
Reference
[1] Evers, M., Wakker, S. I. v. d., Groot, E. M. d., Jong, O. G. d., Gitz-Francois, J. J., Seinen, C. S., Sluijter, J., Schiffelers, R., & Vader, P. (2021). Functional siRNA Delivery by Extracellular Vesicle–Liposome Hybrid Nanoparticles. Advanced Healthcare Materials, 11.
[2] Yu, Q., Zhang, B., Zhou, Y., Ge, Q., Chang, J., Chen, Y., Zhang, K., Peng, D., & Chen, W. (2019). Co-delivery of gambogenic acid and VEGF-siRNA with anionic liposome and polyethylenimine complexes to HepG2 cells. Journal of Liposome Research, 29, 322 - 331.
[3] Yu-Wai-Man, C., Tagalakis, A., Manunta, M., Hart, S., & Khaw, P. (2015). Receptor-targeted liposome-peptide-siRNA nanoparticles represent a novel and efficient siRNA delivery system to prevent conjunctival fibrosis. Acta Ophthalmologica, 93.
[4] Li, L., & An, X. (2016). A novel combined method of thin-film evaporation and a supercritical carbon dioxide technique to prepare a fluorescent siRNA-liposome. RSC Advances, 6, 92115-92119.
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Hello,
I want to load Remedesivir (RNA polymerase inhibitor) into mesoporous nanoparticles (MSNs). The issue is drug is temperature and pH sensitive and it degrades quickly. I need advice on its loading.
1- Should it be loaded to at the last step of MSN synthesis. Problem with this MSNs are extracted later on through reflux and 60 degree temperature is required. It degrades drug.
2- Should it be loaded after extraction making an ice bath but how long it should be kept on stirring?
3- Later I want to coat it with chitosan MSN loaded Remedesivir and then coating with chitosan. I am concerned about leaching and degradation of drug. Should i load drug first and then add drug?
Thank you for your suggestions.
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Apparently, the inclusion of Remdesivir in mesoporous nanoparticles, as such or at the stage of their synthesis. is not good idea, due to the instability of R and, possibly, its low bioavailability. Microencapsulation by complex coacervation, with possible involving CD, may be more frutful approach. Good luck!
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If you prepare drug-loaded nanoparticles but only obtain microparticles (~2,000-4,000 nm), PDI~0.2, how can you reduce the size to reach ~100 nm?
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If your formulation in suspension form, you can use size reducing techniques like High pressure homogenisation or microfluidic techniques for size reduction. This method will be the scalable, reproducible and standardized methods. The selection of nozzle and other equipment parts are dependents on your material and sample. Please refere the equipment experts opinions.
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This question addresses the ongoing challenge of improving cancer therapies by focusing on the development of advanced drug delivery systems that can more accurately target cancer cells, thereby reducing side effects and increasing the effectiveness of treatment. Nanotechnology offers a promising avenue for this research due to its potential to create highly specific, controlled, and responsive drug delivery platforms.
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Hello
A lot of research has been done in this field and various articles have been published in this field. You can see some of them below:
Review of the efficacy of nanoparticle-based drug delivery systems for cancer treatment
Smart drug delivery systems: Concepts and clinical applications
Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation
Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance
Nanotechnology in Cancer Drug Delivery and Selective Targeting
Nanotechnology in Cancer Diagnosis and Treatment
Nanoparticle-based drug delivery systems for cancer therapy
Nanocarriers for safer breast cancer treatment
Investigating the effects of nanotechnology in the process of cancer treatment
A REVIEW ON CURRENT ADVANCES IN NANOTECHNOLOGY APPROACHES FOR THE EFFECTIVE DELIVERY OF ANTI-CANCER DRUGS
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I have prepared some polymeric microspheres from chitosan and PCL. However while performing in vitro degradation study, I found difficulties in both above mentioned methods. Here I am mentioning one-by-one possible methods and their drawback I faced and will appreciate if anyone can give a better and doable solution for the below-mentioned methods?
1) By change in weight of microsphere:
Literature has told to take a certain amount of polymeric microspheres in a tube and incubate with different physiological solutions for a pre-determined period. Then to remove the microspheres from the tube, wash it with d.H2O and re-weigh it. Then to calculate the % of weight loss
(degradation)= Initial weight (W0)- weight at that time (Wt)/W0 X 100
The problem I faced: While washing the microspheres with water at a pre-determined period and centrifugation to settle all the microspheres as pellet and other buffers and water as supernatant, there is a chance of microsphere loss during discarding the supernatant of the washing step. You can't be careful enough because PCL is a hydrophobic polymer and it won't form sticky clot at the bottom of centrifuge tube after coming in contact with water. So, when the last portion of the supernatant is about to leave the tube mouth, it will carry some microspheres with it. So, thereby reducing the original weight of the test sample. So there is no meaning of doing a degradation study if I already got the Wt<W0 because of sample loss.
P.S: I am talking about microspheres whose size range from 50-300 um, just like wheat flour. So don't expect me to visibly avoid sample loss during the discarding process because it's a microsphere, not a bead.
2) By measuring the diameter of PCL microsphere from microscopic image processing software.
I tried another method for doing a degradation study by visible parameters like size. After incubation of a certain weight (mg) of microspheres in 3 different PH of PBS for a predetermined period followed by taking 100 ul of the suspension on a slide and observing under 40X microscope and measuring the change in size of the microsphere by image processing software. However, I didn't get any significant change in microsphere size even after maintaining a narrow range of size distribution while choosing microspheres of an image for analysis.
Apart from that, I didn't observe any swelling of the microsphere i.e. increase in microsphere area or diameter on Day 1, rather a significant decrease in average area and diameter. Usually, in case of hydrophilic polymer incubation in PBS, we are expected to observe initial swelling because of water absorption followed by hydrolysis of the polymeric backbone, which results in size decrease of polymeric microspheres.
The problem I faced: There is no initial swelling or significant degradation of microspheres throughout the study period. Only the change in the spherical shape of microsphere was observed after day5 of incubation in PBS and significant degradation and fungal growth observed around day45.
Can anyone suggest me another doable methodology for checking degradation of PCL microsphere ranging from 30-200 um.
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Two methods:
Do you have access to a particle size analyzer (for example Bettersizer)? This will give you average particle size and particle size distribution. This will provide information on how the distribution changes with time.
Alternatively, prepare the materials with incorporation of a dye molecule. As the micropspheres degrade, dye will be released. You can remove portions over time, centrifuge or filter to get rid of intact microspheres, then take UV-Vis to determine release.
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I want to develop a nanoparticle-based drug delivery platform for burst/instant release of any drug. Kindly suggest ways to do that? What type of release mechanism can be adopted?
Usually, applied drug release mechanisms like pH-sensitive drug delivery works in a sustained release manner, however, I am looking for techniques (external stimuli) that can promote instant release of drug from the carrier. Thanks in advance for your reply.
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If you're looking for external stimuli to disrupt the nanoparticles, then I'd suggest ultrasound. Easy to use and commonly available.
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Hi
I am working on liposome formulation. we are trying for reproduction of the size at range of +or- 20 nm. but Malvern zeta Sizer always showing different size with 2-3 peaks always.
There are number of publications just mentioned the size in number like ZXC +/- AB.
really frustrated with this first problem
and the second problem is losing hope to trust literature publications.
please share your experience, guide me if possible. help me please.
Thank you.
JR
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Hi Raj,
It sounds like your sample has some problem. This can be the case if too polydisperse, liposomes not stable, too big, concentration too low, and the list goes on. You can’t just trust a publication. If you’re following their protocol exactly then I’d recommend to contact the authors, try troubleshooting yourself, or if that doesn’t work then you can ask a company to do the work for you. I recommend LipExoGen who always does an excellent job on liposome preps for our lab and save us a lot of time. Getting the particle size in the range of +/- 20 nm is no problem for them.
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I am looking for a plain/empty gel system, which we can directly buy and load the drug for the purpose of transdermal delivery. Your kind help will be appreciated.
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You can try customized molds to fabricate hydrogel microneedles for transdermal drug delivery.Many hydrogels are commercially available.
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Hello. Recently, I want to inject the adenosine in vivo to see its effect on the behaviors. But I am not sure whether it can cross blood-brain barrier. If it could, I would choose easier drug-delivery way such as i.p. injection. Could any expert give some advises? Thank you.
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Dear Ju Jun,
Adenosine does not cross the blood brain barrier. When adenosine enters the circulation, it is rapidly broken down by adenosine deaminase, which is present in red blood cells and the vessel wall. Thus, adenosine has an extremely short half-life. Therefore, you will need to apply adenosine directly into the brain region as close as possible.
best wishes,
Refik
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I am working on a Speiolite clay-based nanosystem for drug delivery. In order to check the Particle size and zeta potential of the systems what would be the ideal medium to disperse the nanomaterial?
TIA
Please feel free to ask if you need more information
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The correct medium is whatever the clay is dispersed in for its application.
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We synthesized a core-shell magneto-electric nanoparticles for drug delivery application, required layer-by-layer deposition method for the synthesis. How it is employed? What's the exact procedure? Also what will be the expected size range of core and shell?
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It's great to help you out with your research. Layer-by-layer (LbL) deposition is a versatile technique used to create core-shell structures with precise control over the thickness of each layer. It's commonly used for applications like drug delivery where you want to encapsulate a core material within a shell.
Here's a general procedure for employing the layer-by-layer diffusion method to create partial coatings of a shell over the core:
**Materials Needed:**
1. **Core Particles**: These are the nanoparticles you want to coat with a shell.
2. **Shell Material**: The material that will form the shell. This can be a polymer, a charged molecule, or another material suitable for your application.
3. **Solvent**: A solvent that's compatible with both the core and shell materials.
4. **pH Buffer Solutions**: If your materials are pH-sensitive, you may need buffer solutions to control the pH during the process.
5. **Centrifuge**: To separate coated particles from uncoated ones.
6. **Ultrasonicator**: To aid in dispersion and mixing.
7. **Layer-by-Layer Deposition Equipment**: This can be a simple setup, like vials and a centrifuge, or more complex systems.
**Procedure:**
1. **Prepare Core Suspension**: Disperse your core particles in the solvent. You might need to use an ultrasonicator to ensure a uniform suspension.
2. **Prepare Shell Solution**: Prepare a solution of your shell material in the same solvent. The concentration will depend on the desired thickness of the shell layer.
3. **Deposition**: This is where the layer-by-layer part comes in. Here's a simplified version of the process:
- **Dip the Core Particles**: Immerse your core particle suspension into the shell solution. Allow the shell material to adsorb onto the core particles.
- **Wash**: After a certain amount of time, remove the core particles from the shell solution, and wash them with the solvent to remove any unbound shell material.
- **Repeat**: Repeat the dipping and washing steps for the desired number of layers. The number of layers determines the shell thickness.
4. **Characterization**: After the desired number of layers, characterize your core-shell nanoparticles. This can include measuring size, zeta potential, and shell thickness using techniques like dynamic light scattering (DLS) or electron microscopy.
The expected size range of the core-shell nanoparticles will depend on the specific materials and deposition conditions. Typically, you Anjali Krishna G can control the thickness of the shell and, to some extent, the size of the core particles by adjusting factors like the concentration of the shell material and the dipping time.
Remember that LbL deposition is a highly customizable technique, and the exact conditions will vary based on your specific core and shell materials and your desired outcomes. It's essential to consult the literature, perform preliminary experiments, and optimize the process for your application. Good luck with your drug delivery research!
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Anyone Can suggest me Lignin Bio-polymer application and its uses or any research which is currently happening in Lignin Nano-particles or lignin nano-composites materials in human welfare and in drug delivery.
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Thank you for sharing this research.
You can have a look on lignin-based and covalent adaptable networks here.
Kind regards,
Davide
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Write a short summary of 250 words on why mimicking physiological conditions or clinical situation important for translational research. (Free ChatGPT (July 13 2023 around 1100am JST)
Answer from ChatGPT.
Mimicking physiological conditions or clinical situations is of paramount importance in translational research due to its ability to bridge the gap between laboratory findings and real-world applications. Translational research aims to translate scientific discoveries and knowledge into practical solutions that benefit human health. By replicating the complex and dynamic environments found within the human body, researchers can gain valuable insights into the efficacy, safety, and mechanisms of potential interventions.
One key reason for mimicking physiological conditions is to enhance the relevance and reliability of preclinical studies. Human physiology is intricate, and diseases often manifest within a specific physiological context. By recreating these conditions in experimental models, researchers can better understand how interventions may interact with the body and predict their potential effects on human patients. This approach helps to minimize the risk of false positives or false negatives, which can occur when experimental conditions do not accurately represent the clinical reality.
Furthermore, mimicking physiological conditions enables researchers to investigate the intricate interplay between different biological systems. The human body operates as a complex network of organs, tissues, and cells, all interconnected and influencing one another. By recreating this complexity, researchers can study the holistic effects of interventions, uncover unexpected side effects, and identify potential mechanisms underlying observed outcomes.
Additionally, mimicking clinical situations allows for the evaluation of interventions under realistic scenarios. For example, testing drugs or therapies in animal models that mimic the disease pathology, progression, and response to treatment observed in patients can provide valuable data for predicting their efficacy and safety in humans. This approach aids in the selection and optimization of promising candidates for further clinical trials, ultimately expediting the development of new treatments and therapies.
In conclusion, mimicking physiological conditions or clinical situations is crucial in translational research as it enhances the relevance, reliability, and predictive power of preclinical studies. By closely mirroring the complexities of human physiology and disease, researchers can make more accurate predictions about the potential benefits and risks of interventions, ultimately accelerating the translation of scientific discoveries into clinical applications that improve human health.
References.
Filicori, Marco. "Pulsatile gonadotropin-releasing hormone: clinical applications of a physiologic paradigm." F&S Reports 4.2 (2023): 20-26.
Cahill, Catherine M. "Opioid dose regimen shapes mesolimbic adaptations." Neuropsychopharmacology 45.11 (2020): 1777-1778.
Lefevre, Emilia M., et al. "Interruption of continuous opioid exposure exacerbates drug-evoked adaptations in the mesolimbic dopamine system." Neuropsychopharmacology 45.11 (2020): 1781-1792. https://www.nature.com/articles/s41386-020-0643-x
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Mimicking physiological conditions or clinical situations is critically important for the success of translational research. This is due to the fundamental premise of translational research: translating fundamental scientific discoveries into practical, clinical applications.
Accurate replication of the human body's environment helps ensure that the results obtained in the lab can be applicable to real-world scenarios. It enables us to understand the biological and molecular pathways that govern health and disease more accurately, which is essential for creating effective treatments and interventions.
For instance, cells behave differently under in vitro conditions compared to in the human body. Thus, research models that closely mimic human physiology provide a more realistic view of how cells function and interact, improving the reliability and accuracy of findings.
In drug discovery and development, understanding the precise physiological conditions can aid in predicting a drug's effectiveness and potential side effects. In vitro testing often lacks the complexity of the human body, which could lead to incorrect assumptions about drug safety and efficacy. By mimicking physiological conditions, we can better predict how a drug will behave in the body, increasing the likelihood of successful clinical trials.
Furthermore, considering the clinical situation can enhance the relevance of research outcomes. This takes into account the complexities of disease progression, comorbidities, patient lifestyle, and other factors that can influence treatment effectiveness.
In summary, mimicking physiological conditions and considering the clinical situation can enhance the realism, relevance, and potential success of translational research, bridging the gap between lab-based findings and clinical application.
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In relevance to drug delivery, the absorbance of EPIRUBCINE is measured at 480 nm in UV-Spectrophotmeter. Which would be the best selection between UV-Quartz and Glass cuvettes? Is any of this better than the other one or both will give similar results. If anyone can enlighten me on pros and cons of selecting the cuvettes between these two for EPIRUBCINE @480 nm, it would be a great help. Thanks.
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Hello,
I'm working on drug delivery in cancer cells. For that, I prepared slides of adherent cancer cells for confocal microscopy. I fixed the cells with 150 ul of 4% paraformaldehyde for 10 min and mounted the cover slip on a glass slide. Then I stored the slides at -20 degC. After one day I did imaging, I found that cells got flattened morphology and some granular structures were seen inside the cells that were totally different from their morphology. Imaging was also not good. I've some doubts regarding this:
1. Whether the incubation time with paraformaldehyde (10 min) was more than required or storage at -20 degC damaged the cells?
2. What should be the optimum time and volume of paraformaldehyde incubation?
3. At what temperature we can store the mounted slides and for how long?
Please guide me regarding this.
Thank you
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Hello,
I usually incubate my immunofluorescence specimens in a 4% paraformaldehyde solution for 15 minutes and I have never faced any problems following this prodedure (I use about 200 to 250 μl for each slide). I store fixed cells at 4 degrees Celsius in PBS solution containing sodium azide until staining. I've tried keeping them for about 8 weeks and it worked just fine. Just make sure they stay hydrated and sealed to avoid contamination.
Hope this helps,
Best regards,
George
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I am preparing polymeric water in oil (w/o)emulsion where I am using Span-80 as a surfactant. In several papers, it's given that first the emulsion has to be heated around 50-60 degree C followed by keeping the emuslion solution in ice box. By doing this method, I got a microsphere but there is difficulties in capturing the image, which is because of the clumping of microspheres. Later, I read a few Q&A where people mentioned that high temperature is not good for the stability of emulsion as it will degrade the layer of surfactant that is present on top of every microsphere. Usually, it's the surfactant that helps to keep the microspheres away from clumping and keep it separated, which will be actually good for capturing microscopic image.
Now I am confused whether I should heat the emulsion at 50-60 degree C or directly prepare the microsphere, while keeping the emulsion solution in ice box.
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The stability and behavior of emulsions can be influenced by various factors, including temperature, surfactant concentration, and formulation conditions. In your case, it seems that you are experiencing clumping of microspheres when heating the emulsion and are concerned about the degradation of the surfactant layer.
Surfactant Stability: Heating the emulsion at higher temperatures can potentially lead to the degradation or destabilization of the surfactant layer around the microspheres. This can result in poor dispersion and increased clumping of the microspheres.
Cooling Method: Cooling the emulsion in an icebox after heating can help promote the solidification or gelling of the emulsion, leading to the formation of microspheres. The cooling process can enhance the physical stability and prevent clumping by slowing down molecular motion within the emulsion.
Alternative Cooling Techniques: Instead of using high temperatures followed by cooling, you may consider exploring alternative cooling techniques to minimize the potential degradation of the surfactant layer. For example, you could try using a lower initial temperature during emulsion preparation or implementing a gradual cooling process to achieve the desired microsphere formation
Surfactant Selection: The choice of surfactant is crucial for emulsion stability. It is possible that the Span-80 surfactant may not be the most suitable option for your specific emulsion system. You could explore other surfactants or surfactant blends that offer improved stability and dispersion characteristics for your microspheres.
Experimental Optimization: Conduct a systematic study by varying different parameters, such as surfactant concentration, emulsion formulation, temperature, and cooling conditions, to determine the optimal conditions for microsphere formation with minimal clumping.
To resolve your dilemma, you may consider adjusting the emulsion preparation method by avoiding high temperatures altogether and focusing on alternative cooling techniques. However, it is essential to conduct additional experiments and evaluate the stability and behavior of the resulting emulsion under different conditions to identify the most suitable approach for your specific microsphere preparation.
Hope this helps.
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Paclitaxel is a hydrophobic drug therefore I dissolved it in DMSO. The issue with DMSO is it has an OD value around 260 nm and the lambda max of paclitaxel is also 263 nm. Stock solution of drug is prepared in DMSO by dissolving 10 mg/mL and further 2 ug/mL of drug dilution was prepared in DMSO as well but OD value is 1.5. I need assistance how to cut the value of DMSO so I can find out the actual peak of drug and then concentration.
Thank you for your help!
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Henry Kolge I diluted DMSO to 9:1 (DMSO:water).
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With the aim of better loading of gold nanoparticles in drug delivery and cancer treatment.
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Dear Kaushik Shandilya , I appreciate your advice. They are literate and detailed, but I would like to make an important note about your phrase "Smaller nanoparticles may have more surface area available for interactions". It was necessary to write "Small nanoparticles with a larger specific area (m2/g) have a larger surface for interaction." After all, small nanoparticles have a small surface.
Best regards,
Yuri
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The goal is to load Doxorubicin on BSA nanoparticles for drug delivery with high affinity.
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Thank you very much for your kindness and attention. Your detailed and complete explanation will be a good guide for me.
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Hey all
Does chitosan dissolve properly in 1% acetic acid or is it a colloidal solution? I have attached an image for clarity and the source from where I got the protocol.
The following represents the protocol I followed for the synthesis of Chitosan nanoparticle.
1. Weighed 1.25g of Chitosan powder (from Sigma)
2. Made 1% (v/v) acetic acid solution in 500mL double autoclaved water.
3. Added 1-2 mL of tween 20
3. Stirred the solution at room temperature for 24hrs
But the particles are not dissolved and have formed a kind of colloidal solution with froth over the top.
If anyone out there has a standard protocol for making Chitosan nanoparticles, kindly provide it. Also please point out my mistake.
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Thank you Eloy Pena Rodríguez for your suggestion. I did add 1% glutaraldehyde.
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can we formulate nanoparticles with Guar gum and pectin to form a carrier for colon-targeted drug delivery?
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That's a very interesting question. Based on my web search, it seems that guar gum and modified citrus pectin can be used together to formulate nanoparticles for colon targeted drug delivery. According to one study (Pectine Polymers...), guar gum and pectin can enhance the colon targeting of solid self-nanoemulsifying drug delivery systems (SNEDDS) by protecting the active molecules from the acidic environment of the stomach and small intestine and by being degraded by the colonic microflora (pharmaceutical and drug...). Another study (guar gum- an over...) reported that pectin polymers have various advantages for colon-targeted antitumor drug delivery, such as biocompatibility, biodegradability, nontoxicity, and controlled release properties. Pectin can also inhibit tumor growth and reduce metastasis rate by itself (guar gum-an...). Therefore, it seems that guar gum and modified citrus pectin can be a promising combination for colon targeted drug delivery of nanoparticles.
Source:
(1) Development of Guar Gum-Pectin-Based Colon Targeted Solid Self .... https://www.mdpi.com/1999-4923/14/11/2384.
(3) Pectin polymers for colon-targeted antitumor drug delivery. https://www.sciencedirect.com/science/article/pii/S0141813020331470.
(4) Pharmaceutical and drug delivery applications of pectin and its .... https://www.sciencedirect.com/science/article/pii/S2405844022019429.
(5) Development of Guar Gum-Pectin-Based Colon Targeted Solid Self ... - PubMed. https://pubmed.ncbi.nlm.nih.gov/36365203/.
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How does wide band gap of iron oxide nanoparticles affects drug delivery system and magnetic resonance imaging?
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The excellent query you raised.
As far as I know, bandgap is a critical property of materials used in drug delivery and diagnostic imaging. In drug delivery, materials with specific bandgap properties are used to facilitate the controlled release of drugs into the body. In diagnostic imaging, materials with specific bandgap properties are used to generate contrast signals that can be detected by imaging techniques such as magnetic resonance imaging (MRI).
  • Iron oxide nanoparticles (IONPs) are a popular material for drug delivery and diagnostic imaging applications due to their biocompatibility and magnetic properties. The wide bandgap of IONPs (typically around 2 eV) allows them to absorb and emit light in the near-infrared (NIR) region, which can penetrate deeply into biological tissues. This property is useful in drug delivery because it allows for the targeted release of drugs in specific areas of the body.
  • In drug delivery, IONPs can be functionalized with drugs or other therapeutic molecules and then delivered to the target site using an external magnetic field. Once at the target site, the IONPs can be triggered to release the therapeutic molecules by applying a NIR laser. The wide bandgap of IONPs also allows them to act as photothermal agents, which can be used to heat and destroy cancer cells.
  • In diagnostic imaging, IONPs are used as contrast agents for MRI. The magnetic properties of IONPs cause them to behave differently in a magnetic field than surrounding tissues, which generates a contrast signal that can be detected by the MRI scanner. The wide bandgap of IONPs also allows them to be excited by NIR light, which can be used to generate photoacoustic signals that can enhance the contrast of MRI images.
Overall, the wide bandgap of IONPs plays a critical role in their ability to act as both drug delivery vehicles and contrast agents for diagnostic imaging.
I hope this clears your doubts. Good luck with your research!
Best wishes & regards,
Vishwajit
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Hi All, I am working with A549 cell line and trying to culture spheroids using low attachment 96 well plates. So far I have attempted some different seeding densities from 2000 to 10,000 cells and can either form very large spheroids (700-900um), which are more compact and have a spherical defined shape, or alternatively smaller spheroids (still fairly big though around 500um) are less compact and not completely spherical. However for my experiment where I wish to add drug compounds (2D IC50 approx 1uM) I am not observing significant size/morphology change on the larger spheroids despite at least a 10uM concentration for 1 week. I am thinking possibly I can try to treat smaller spheroids for a more obvious visual change. Does anyone know how i might successfully make small compact spheroids (less than 500um) which are reproducible with this cell line? Thanks in advance for any help someone may be able to provide.
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Of course, time is a significant factor for spheroids' size and viability of cells, due to when you seed the cells to the generation of spheroids after the cells are in the proliferative stage. More time (days) can lead to the big size of spheroids, in addition, the cells located in the core zone are suffered from nutrients, oxygen, and ...
I suggest you set up the best time to achieve reliable results too
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As hyaluronic acid hydrogels are exteremly hydrophile, is there any possible method to modify them to have hydrophobe hyaluronic acid?
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Thanks all for the worthful recommendations
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i am currently looking at a nanoparticle formulation for drug delivery to the brain. I want to be able to test the formulation and see if it has any in vitro activity as a drug delivery system
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dialysis bag diffusion technique
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As it is challenging to reach drug into the brain due to BBB (blood-brain barrier) which contain Tight junctions. But other Blood vessels also have tight junction and no perforation. So why BBB is different from other capillaries?
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Malcolm Nobre, Thank you very much for your answer.
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Hello everyone
I Load apolipoprotein on extracellular vesicles (EVs).
After centrifuging, I have EVs, apolipoprotein, and also loaded apolipoprotein. How I can separate them?
And also confirm that?
Thanks for your suggestions.
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after doing centrifugation collect the solid layer and go with that.
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Hey Guys
Which among the above mentioned is most suitable material for nanoparticle formulation and targeted drug delivery ?
thank you
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Have a look at following passages from our recent publications V H Krishna Prasad :
4.2. Nanoliposomes with Surface-bound Nanoparticles
One of the limitations of liposomes is their propensity to aggregate, fuse, and create larger vesicles. This phenomenon especially occurs with nanoliposomes smaller than 100 nm. This significant size increase due to fusion limits the ability of the lipid vesicles to deliver therapeutic agents to the target cells. Using a protective coating like polyethylene glycol (PEG) is a popular strategy to stabilize liposomes against fusion. Another strategy is using charged nanoparticles ab- sorbed into the head groups of surface lipids without any non-specific interaction.
...
Source:
Mehrarya, M., Gharehchelou, B., Kabarkouhi, Z., Ataei, S., Esfahani, F. N., Wintrasiri, M. N., & Mozafari, M. R. (2022). Functionalized Nanostructured Bioactive Carriers: Nanoliposomes, Quantum Dots, Tocosome, and Theranostic Approach. Current Drug Delivery, 19(10), 1001-1011.
and:
5.2. Long circulating stealth liposomes and nanoliposomes
Intravenously injected conventional vesicles are mostly eliminated from the blood circulation, after opsonization, by the cells of the immune system that are mainly present in the liver and spleen [60]. Opsonization is the process by which liposomes are marked for ingestion and elimination by the macrophages and phagocytes. Inclusion of certain polymers (e.g., polyethylene glycol (PEG), polyhydroxyethyl L-asparagine (PHEA), etc.), or incorporation of glycolipids (e.g., monosialoganglioside) into liposomes and nanoliposomes, prevent opsonization and result in sterically stabilized vesicles [61-63].
...
Source:
Mozafari, M. R., Torkaman, S., Karamouzian, F. M., Rasti, B., & Baral, B. (2021). Antimicrobial applications of nanoliposome encapsulated silver nanoparticles: A potential strategy to overcome bacterial resistance. Current Nanoscience, 17(1), 26-40.
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I want to know any synthetic or natural polymer with same type of acidic conditions solubility of chitosan for drug delivery.
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Just like there is a range of zeta potentials that indicates whether Nanoparticles in solution are stable or not, what range of zeta potential qualifies Nanoparticles for use in drug delivery?
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Vinod Kumar A small amount of research on RG and the original literature (Riddick) will debunk the '30 mV' myth for charge/electrostatic stabilization. A good starting point is here:
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I need to try delivering a certain drug to mice's brains via Intracerebroventricular injection. It wasn't done before so I don't know which concentrations and volumes I should try. What is the usual approach for testing drug delivery via ICV?
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If I got you correctly, then you want to test a novel drug which has not been reported before. If so, then the concentration should be determined by using >2 doses to compare the best one for your study. This can be done by doing behavioural and one more validating test viz. biochemical or histological tools. And concluding the best dose-response plot out of 3 for example.
However, if you want to know the common practice for calculation of concentration then it depends on the body weight of the animal (mice) in your case. Then comes the physical form of drug viz. solid or liquid and its miscibility. If liquid it is much easier, just go for different % (example: 1, 2, 3, 4...) in increasing order and mix it with aCSF (if lipophobic) or citric acid/ DMSO (if lipophilic). this can be achieved by mixing V/V. If the drug is salt then you have to go for preparation of a solution with different concentrations in weight/ vol. Again, you should keep the miscibility in mind while choosing the diluent. Finally, comes the volume, when you select volume you have to calculate that how much volume of the drug preparation/solution will have your desired concentration.
I hope you you should also think about the rate of delivery of the drug (ul/min) at the next phase. Which totally depends upon how much volume you want to deliver and the region of interest viz. low volume and ventricles can be injected with higher rates viz. 1-2ul/min and big volume and solid tissue can be injected with lower rates viz. 0.5ul-300nl/min.
Aforementioned things are major factors i do keep in mind while trying out a drug dose study especially through ICV route. But, I may miss out few minor things. Have a look at the document (attached) I have used while working with the ICV-STZ model in my PhD. Hope this will help you a bit.
With regards,
Avishek
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I want to use silica coated supermagnetic iron nanoparticles loaded with anticancer drug - Doxorubicin for drug delivery. Will simple loading work for this? Or should I do some chemical modifications?
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You are most welcome dear Saniha Ajith . Wish you the best always.
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I am using Tween-80 as the surfactant and Glutaraldehyde as a crosslinker for my Ch microsphere formation. Although most have used span-80, few people in research gate also suggested tween-80 can be used. But I want to know what is the concentration.
Also want to know the following parameters:
1) How much con: of Glutaraldehyde will be used as the stock is of 25%? As Some paper has written they used 25% aquous solution of GA, I am confusing how come they use 25% aquous conc: as working where the stock bottle itself written 25%.
2)What is the easy washing method for microspheres after filtering it from the liquid parafilm suspension?
3) What is the optimum drying method for a microsphere? Should I use hot air oven or normal air dry 1st followed by hot air oven.
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Thank you for clearing my doubts.
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I'm currently working on exploring the anti-inflammatory effects of a purified plant extract. The compound of interest is a pentacyclic triterpenoid, which is very insoluble in water. This makes drug delivery a bit of a challenge. I'm considering a distilled water/DMSO mixture to act as the vehicle for the compound, which will be administered either through gavage or intraperitoneal injection in mice (C57BL/6). However, since I'm evaluating the anti-inflammatory properties of the compound, I'd like to limit any possible interference from the DMSO, which I know can exhibit anti-inflammatory activity in some doses. Can anyone suggest a possible range of concentrations for DMSO which would not exhibit this anti-inflammatory effect?
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you're welcome!
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We are trying to design Mesoporous Silica Nanoparticles for breast cancer treatment by PhotoDynamic Therapy.
And we are challenging with a question that Which ligand should we add onto the particle for attaching only breast cancer cells when the particles are added into the tumor cells directly by the vaccine (intra-tumoral injection).
Our ligand choice is Anti-HER2 antibody, HA.
We try to research that it is a good choice for us.
#Ligand #HyaluronicAcid #DrugDelivery #BreastCancer #PhotodynamicTherapy #SilicaNanoParticles #Ligand #Antibody #IntraTumoralInjection
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If you administrated your nanoparticles locally (intrtumor injection) , I think you needn't design the specificities or targeted strategies of your drug delivery. Because from tumor biology perspectives, the aggressive cancer cells are always infiltrating into surrounding microenvironment with some physical or immune barriers. Therefore, even if you treated the cancer cells by monoantibodies, you can't kill the tumor totally.
However, if your delivery strategies are intravenous injection, tageted therapy is the most important principle that you must take into considerations. So, in this context, my suggestions are that what kind of tumor you are goning to treat decides what antibodies you are attaching. As is known to all, breast cancer has less than three kinds: ER+, HER2+, and trible negative (luminal). I suggest you could widen your antibody choices for HER2+ breast cancers. Do the nanoparticles have a good ability to load Antibodies? What's the relationship between your breast cancer cells with your mesoporous NPs, drugs, and Antibodies? ...
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Magnetic nanoparticles like ferrites possess self-heating properties and can be used in biomedical applications like magnetic hyperthermia, drug delivery, etc. What are the other applications in which this property can be utilized except biomedical applications?
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Self heating property of Magnetic nanoparticles can be used for hyperthermia application by governing the chemotherapy drug, and can also be used for radiation therapy. Magnetic particle heating can be accomplished at depths necessary for tumor treatment.
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I have attempted using DMSO as a drug-delivery vehicle for a water-insoluble drug but it tends to precipitate out after injection into mice. I am considering trying this with a NMP/PEG-300 formulation instead but cannot find any literature of this ever having been done before. Anyone have any insight into this method?
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Jose Chavira can you share some of this literature
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Hi.
Is negative zeta potential suitable for liposomes or positive zeta potential?
Some articles have suggested that a negative zeta potential is appropriate for the liposome, and some articles have suggested that a positive zeta potential is a more appropriate factor for liposome delivery of the drug.
Please leave your valuable comments on the effect of zeta potential on drug delivery by liposome
Thank you.
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Dear Mohmmad Majdizadeh, as far as the drug delivery is your goal, there are various parameters involved in the influence of surface charge of liposomes : cellular uptake, binding, gelivery mechanism, circulation time, stability in the bio-liquids are few to mention. Please have a look at the following documents. My Regards
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If so, we're hiring! - come and join our team to help develop the next generation of intelligent, wearable drug delivery devices. Research opportunities now available in microsensor integration, transdermal delivery and microfludics, and system electronics/communications. Further details available from Dr Conor O'Mahony - feel free to discuss with us!
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That's a very interesting research domain. I wish you best of luck
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The unique physicochemical properties of CNTs make them among prime candidates for numerous applications in biomedical fields including drug delivery, gene therapy, biosensors, and tissue engineering applications.
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Carbon nanotubes (CNTs) represent one of the most studied allotropes of carbon. The unique physicochemical properties of CNTs make them among prime candidates for numerous applications in biomedical fields including drug delivery, gene therapy, biosensors, and tissue engineering application
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Limitations of carbon dot or carbon dot based products for commercialization.
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We have tried to address a few things in this direction in our latest review article.
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For a depot injection designed for absorption by macrophage action, which injection route would be optimal to have most drug introduced into the lung by the lymph vessel?
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Dear Dr Min Gui Jang . See the following useful RG link:
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Greeting
I am curious to know whether it is possible to explain and analyze targeted drug delivery methods with the mathematical and physical relationships that govern them, such as the Peppas Higuchi model?
What other models are available in this field?
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Dear Farrokhfar Valizadeh Harzand, many approaches are dealing with modelling drug delivery with respect to the stimulus-responsive vehucules. Please have a look at the following documents. My Regards
DOI: 10.5772/intechopen.73678
10.1016/j.compbiomed.2021.104238
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Why nature-based products are considered biocompatible for drug delivery although many natural products can be toxic or dangerous
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They are products of biosystems and compatible with majority of biochemical reaction, pathways and products of primary, and secondary metabolites. The receptor affinity is of prime importance for a natural product to bind and produce effects, the choice of the receptor or exactly the natural products pharmacophore fitting the receptor type will produce the effects the receptor is responsible for. Not all natural products bind to many receptors, rather specific in nature. Multivalent binding and specific receptors produce their effects, at times harmful as their intrinsic property.
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I am working on nanoemulsions for topical drug delivery. However, due to limitations with the equipment available, I am wondering is it possible to prepare my nanoemulsion in small volume, and proceed to dilute it with water? Will this process causes breakdown of the micellar structure of NE?
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O / W nanoemulsions have a certain composition according to the amount of water, surfactant, water-insoluble drug. These ratios can be changed within certain limits. If you go beyond these limits, you can destroy the nanoemulsion or transform it upon dilution into a W / O microemulsion. Therefore, dilute by adding water drop by drop and observing its condition.
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Hope that everyone will be quite fine sir I am working on Self nanoemulsyfying drug delivery of low orally bioavailable drugs but em facing some problem my formulation have zeta potential of -10 and PDI of 0.42 can we consider it as stable and accepted .
Second those who know the concept of self nanoemulsyfying drug delivery system when it taken once directly goes into the gut and form a nanoemulsion due to GIT motality then still the PDI and zeta potential can be considered as standard like conventional nano emulsion because the face problem after dilution with aqous phase and in shelf life ???
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Hello Sir!
In continuation of @john Francis i would like to add few points into it, Sir, you have enlisted very effective points but in addition to stearic and electrostatic interaction ,drug delivery plays a vital role in defining charge and size of the particle. For example: If you need to deliver any anionic body i.e., nucleic acids etc. you cannot continue with the charge you mentioned i.e., -10.whereas in conventional drug deliveries without anionic counter parts your can proceed with this specific zeta potential depending upon the target binding efficiencies. For your ready reference, i am attaching one such approach, kindly have an overview.
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Dear all,
Good day.
I'm currently working on a formulation involving an extract from garlic, allicin and will be moving onto the in vitro drug release test. Based on my preparation for the standard curve via UV Vis spectroscopy, allicin is temperature sensitive and has to be placed on ice (the absorbance seems to fluctuate if its left at room temperature over time). The drug release assay seems to be conducted at 37 °C most of the time hence, I'm wondering if it would be a problem if I'm planning to measure the release of allicin from my formulation via UV Vis during the in vitro drug release assay?
Thank you in advance for your time.
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Adam B Shapiro Hi Dr. Shapiro. I've attempted the spectrum scan in the spectrophotometer and the shoulder of the peak appears slightly before 240 nm but the absorbance was > 2.0 even at 0.00125 mg/mL. I believe I have no option but to resort to HPLC as you previously recommended and as reported in previous papers. Thank you so much for your guidance. I am truly grateful for your help.
Kandluri Geethika Thank you for sharing. I shall bear your advice in mind when I conduct the drug release assay.
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What is the best dosage of tetracylcline in vitro effect? i dont know the theurapetic window or index of this drug. please help me guys.
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Hello, can anyone please named few potential drug delivery technologies that you think are novel and unique. Our comapny is looking to buy few drug delivery technologies that can serve us to compete for now and few next years. Suggestions are highly appreciated. Thanks in advance.
Regards
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Current trend is Nanotechnology based drug delivery systems like nanogels, Hydrogels for wound healing, surgical sprays, Monoclonal antibodies are in high demand in this covid state and many companies are even having patents.
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For calculation of drug release via Franzcell diffusion, do you consider the whole volume of the media cell? or you just divide the drug concentration by the amount of the initial drug?
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M. R. Mozafari Thank you.
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Hi,
I wanted to know about the drug release behaviour under HPLC method.  
I am trying to get the peak for release profile of nanoparticle-Paclitaxel drug in 1X PBS for different time points whereas I got the peak for loading. Nanoparticle is calcium phosphate. Could anyone suggest the possible solution for the same.
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When doing drug release of PTX, we dissolve NPs in PBS 1X pH 7.4. But when we calculate the drug release of PTX by HPLC, we need to make a standard curve. So what is the solvent we can use? Because maybe PTX can not be dissolved in PBS to make a standard curve. Is there anyone helping me?
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Is there any software available to simulate the behaviour (growth, differentiation etc.) of different cell type on an implant surface.
Also, software related to simulation of drug loading and release from a drug carrier and its pharmacokinetics.
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Thank You Riaz & Tejas
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I want to check for apoptosis in the co-delivery system. One of the drugs that are simultaneous with another drug in nanocarrier is prodigiosin. Since the emission wavelength of prodigiosin was similar to that of propidium iodide, necrosis was detected instead of apoptosis. How can I improve my apoptosis results?
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You may use different dyes available for DNA binding. Cell trace is one of the example, which is excited by violet laser.
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Dear all,
Greetings. I purchased MWCNTs, which are >98% carbon basis, O.D. × L 6-13 nm × 2.5-20 μm(Sigma, cat no. 698849) and oxidised them using the method described by Thi Mai Hoa, 2018. A total of 100 mg of pristine MWCNTs is added into 20 mL of 4 M of HNO3 and 10 M of H2SO4 (1:3) and left stirring for 18 h at room temperature after which, it is coated with chitosan in 1% and 2% acetic acid as described by Sobh et al., 2019.
Previous papers have emphasised the importance of the oxidation step to prevent the aggregation of MWCNTs thus, I decided to conduct the dispersion assay as described by Singer et al., 2018 (in their paper,). A total of 20 mg of pristine, oxidised and coated MWCNTs were dispersed in 20 mL of water and sonicated in a waterbath for 30 min followed by an hour of sedimentation. The mixtures were observed over a week. Based on my observation, the pristine MWCNTs sank to the bottom after 24 h. However, the oxidised MWCNTs also appeared to be settling after 48 h (as observed in the picture). The MWCNTs coated with chitosan appeared the same from Day 1 (Picture labelled 1 h).
How important would the oxidation step be in this case? Would it be safe to utilised the coated MWCNTs since it shows no signs of settling? I've attached some pictures from the first hour and a week after sonication. I would appreciate your feedbacks or recommendations. Thank you.
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If the effect of MWCNT on rate is assessed, the sample will be abruptly released in the early stages (~ 1 hour), but subsequently the rate will be reduced, showing a sustained release.
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I am searching for better biorobots for targeted drug delivery. Please suggest some microbots/nanorobots which were used in the cancer drug delivery system with working.
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Hi,
In a recent literature, it is claimed that: "Currently available drug delivery systems depend on systemic circulation and lack the navigation ability required for accurate targeting. Micro/nanorobots with motion ability can meet these features, to a certain degree, and represent an attractive prospect."
10.3390/pharmaceutics12070665
Also, see attached Figures.
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Current commercially available implantable pumps are osmotic pumps (www.alzet.com) and programmable micro infusion pumps (www.iprecio.com) in the preclinical/drug discovery market. What would Users like to see in next generation commercially available pumps? (must have, nice to have, short term requirements, long term dream …… in this preclinical/drug discovery market –(non-clinical applications)
For inspiration – commercially available implantable clinical pumps.
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New and Important references on Implantable Pumps out in 2020 & 2021. One new book to come out in September 2021. Re-sharing Open Access Publication <Microdosing for drug delivery application—A review> Final Version. Sensors and Actuators A: Physical Volume 330, 15 October 2021, 112820 https://lnkd.in/gnvnwr5 A review of peristaltic micropumps Sensors and Actuators A: Physical, Volume 326, 1 August 2021, 112602 https://lnkd.in/gGh4ZSR Intelligent automated drug administration and therapy: future of healthcare. Drug Deliv. and Transl. Res. (2021). https://lnkd.in/gDKMUie Chapter 7 - Implantable drug delivery devices Drug Delivery Devices and Therapeutic Systems Developments in Biomedical Engineering and Bioelectronics 2021, Pages 129-156 https://lnkd.in/gw5RsTj Implantable Technologies: Peptides and Small Molecules Drug Delivery Editor: Ved Srivastava. https://lnkd.in/gTapPCS Royal Society of Chemistry. Copyright year 2022 Print ISBN           978-1-83916-222-0 Join Dr. Christian Schnell in his upcoming webinar on <Programmable pumps for compounds delivery in oncology research: implication for refinement and reduction of animal use.> https://bit.ly/3sWgYRh
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I am planning to deliver a drug in C57BL6 mice and the desired concentration is 25mg/kg/day. Assuming that the average weight of the mice is 40 grams and the drug has to be delivered for 2 weeks straight, how much drug do i need to perform the experiment, how to prepare the stock and what kind of osmotic pump should I use?
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I agree with Michael Stonebrook. Essentially you want to deliver 1mg/day for a 40g mouse. You therefore need a pump that can deliver 1mg/24h.
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Hi!
We are using microfluidics to fabricate gel beads. Though they have a central mean, the distribution presents a quite discrete distribution. However for our application we need to strictly rid off bead >60um.
This is not a usual size in cell strainer and I cannot find 60um cell strainer in China. Instead, I ordered some stainless steel net. The problem is that the steel net is quite elastic. Even with pole size to 55±2um, there are still seldom 60-61um beads remain.
Is there any other method to rid off the >60 bead?
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There are different possibilities:
If the particle's density differ from the liquid: centrifugation may do it.
Dielectric materials may get attracted and separated by electrical fields according the their surface area. I don't know if this matches hydrogel-particles.
Otherwise shear flow can also separate according to particle size.
Best regards, Claus / Biophysical Tools GmbH
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Dear Researcher
Respectfully, I am working on drug delivery.
I synthesized Zn-MOF. I am going to load Doxorobicin on it and the study the derivery behaviour.
I tried several times to load. but I did not succeed. Apparently, the drug is not loaded on MOF. Could you Please guide me why not loaded? Theere are several hydroxyl, carbonyl and ether functional groups on the doxorubicin and it seems to be loaded easily. The results indicated no loading on MOF.
Regards
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Sir for conjugation/linking or loading you can try with linkers as well as catalyst which will definitely enhance the loading of your drug. You can refer this article also I have attached .Hope it will help
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Hi,
I am very new to the study of/working with hydrogels and have not gotten the chance to get into a lab because of covid. So all of my knowledge comes from scientific literature I’ve read over the past 1-2 months, and is very limited. I am trying to make biocompatible microspheres (.5 to 5 microns) that degrade extremely quickly (1-2 minutes ideally). I apologize if my questions are obvious, but I would greatly appreciate any suggestions on how to make this happen. I found several articles cite that pure PEG degrades quickly around 400 degrees, but was wondering if a hydrogel made with PEG would degrade at a lower temp? Would a thermosensitive element to the hydrogel even be necessary at high temps like this, or would complete degradation happen first? What would the timeframe look like for degradation at this temp? I also read a paper that showed the thermal degradation pathways of PEG; is there any concern of accumulation of these products in the body (this one is a major concern, I was thinking a super high water content would help this)? Lastly if used for drug delivery, how fast could complete drug delivery happen if the microspheres were kept dry (with a very small drug and very large pores), once introduced to water and swelled (with or without high temps and heat degradation)?
The most important thing is to end up with biocompatible microspheres that degrade extremely quickly, so it doesn’t even have to happen via heat or with PEG specifically. Any pushes in the right direction (or advice if I have any glaring misunderstandings) would be much appreciated!
Thanks in advance!
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Go for ferther review to hydrogel formation. Polymer degradation is exchangeable by greater hydrophilicity in backbone or end group, lesser crystalinity, lower avg MW, etc.... antioxidants can use for stabilization of polymers from thermal degradation. You should try with variety of polymer like PVP, etc.
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Friends,
I want more information about role of chiral drugs on drug delivery based on pharmacology, pharmacokinetics, pharmacodynamics, recepter binding, dose, potency , toxicity, safety with lot of examples. If you have any reference materials like article, book, or other formats and you please send to me.
Thanks you.
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Hi
"enantioselective pharmacokinetics" please check the keyword in google or NCBI.
geometrical isomers have different physicochemical characteristics for example pKa, the same problem cover diastereoisomers.
Enantioselective PK may affect absorption:
D-dopa is less absorbed than L-dopa
D-methotrexate is less absorbed than L-methotrexate
cis - lycopene is absorbed to a greater extent than trans - lycopene
L - cephalexin inhibits the absorption of D - cephalexin from the gut
Enantioselective PK may affect distribution:
  • impact on affinity to blood proteins
  • impact on affinity to transporter systems
  • competition between different form
  • different redistribution with bille depending on racemate
R-methadone has a greater volume of distribution than S-methadone
R - (-) - disopyramide binds less to blood proteins than S - (+) - disopyramide
Cis-cis - mivacurium has a larger volume of distribution than cis-trans, trans-trans
S - propranolol binds more strongly (competes) with plasma proteins than R - propranolol
R - sulbenicillin binds to plasma proteins weaker than S - sulbenicillin
R - latamoxsef binds to plasma proteins more strongly than S - latamoxsef
R-carbenicillin binds to plasma proteins more strongly than S-carbenicillin
Metabolism & Enantioselective PK:
R - propafenone delays the metabolism of S - propafenone
S - nitrendipine is an inhibitor of R - nitrendipine metabolism
R - verapamil is less affected by the first-transition effect than S - verapamil
R - ketoprofen in most species is transformed into S ketoprofen (rodent, dog, monkey, horse, cat) the Asian elephant is the only species that converts S into R
A very interesting case is a chiral inversion in the liver (see examples below)
flobufen (Skalova L. et al 2001)
ibuprofen (Doki K. et al 2003)
pranoprofen (Imai T. et al. 2003)
ketoprofen (Lees P. et al. 2003)
fenoprofen (San Martin M.F. et al. 2002)
albendazole (Virkel G. et al 2002)
thalidomide (Erikson T. et al. 2001)
clopidogrel (Reist M. et al. 2000)
D-leucine (Hasegava H. et al. 2000)
thiaprofenic acid (Erb K. et al 1999)
pantoprazole (Masubuchi N. et al. 1998)
styripentol (Tang C. et al. 1994)
lifibrol (Walters R.R. et al. 1994)
Tolperizon (Yokoyama T. et al. 1992)
Stereoselective elimination:
R-methadone has a longer half-life than S-methadone
R-ibuprofen has a shorter half-life than S-ibuprofen
(-) - mefloquine has a longer half-life than (+) - mefloquine
R - (-) - ketamine inhibits the elimination of S - (+) - ketamine
(+) - terbutaline inhibits tubular reabsorption of (-) - terbutaline
R - sotalolol reduces the renal clearance of S - sotalolol
R - flurbiprofen is excreted from the bile to a greater extent than S - flurbiprofen
R - carprofen is secreted from the bile to a greater extent than S - carprofen
R - sulbenicillin has a lower renal clearance than S - sulbenicillin
R - (+) - propranolol is eliminated more slowly than S - (+) - propranolol
Z - doxepin has a stronger antidepressant effect than E - doxepin
Pharmacodynamics:
Z - doxepin has a stronger antidepressant effect than E - doxepin
S (-) bupivacaine is less toxic than racemic bupivacaine
Of course, it's only the peak of the iceberg so, please check:
.... now > 1000 results ....
examples with references are available in my free e-book (polish version only)
Best regards
Tomasz
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Hi to all!
I am currently working on sequential glucose and oxygen delivery in tissue engineering field and I need to choose specific tissue and cells to work on. I wonder that which tissue need the highest amount of glucose during the first days of implantation. is there any valid reference reporting concentration of normal glucose consumption rate in different tissues?
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As for as the oxygen demand is concerned the heart, followed by kidneys, brain and liver tops the list. The glucose demands is high for the brain. The demand is dependent upon the metabolic rate. The cancerous tissue also has higher demands for the glucose.
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I am currently studying a proteolytically stable peptide that transiently increases blood brain barrier permeability. While the results suggest that it could facilitate drug delivery to the brain, we are interested in assessing the potential downside of such a strategy.
Primarily, we are worried about neuroinflammation. My lab does not have the facilities to properly detect neuroinflammation. Does anyone know of any lab, core facility, or private company that offers services that can determine whether or not the peptide we are testing can lead to neuroinflammation?
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Interesting detail, Gert Fricker - but how to recognize these biomarkers' pathogenic/clinical relevance?