Expert Opinion on Drug Delivery

Description

  • Impact factor
    4.87
  • 5-year impact
    5.13
  • Cited half-life
    3.70
  • Immediacy index
    0.50
  • Eigenfactor
    0.01
  • Article influence
    1.23
  • ISSN
    1744-7593

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy. Areas covered: This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and overall drug efficacy. By comparing spherical and nonspherical nanoparticles, they establish some general design principles to serve as guidelines for developing the next generation of nanocarriers for drug delivery. Expert opinion: Pioneering studies on nanoparticles show that nonspherical shapes show great promise as cancer drug delivery vectors. Filamentous or worm-like micelles together with other rare morphologies such as needles or disks may become the norm for next-generation drug carriers, though at present, traditional spherical micelles remain the dominant shape of nanocarriers described in the literature due to synthesis and testing difficulties. The few reports that do exist describing nonspherical nanoparticles show a number of favorable properties that should encourage more efforts to develop facile and versatile nanoparticle synthesis methodologies with the flexibility to create different shapes, tunable sizes and adaptable surface chemistries. In addition, the authors note that there is a current lack of understanding into the factors governing (and optimizing) the inter-relationships of size, surface characteristics and shapes of many nanoparticles proposed for use in cancer therapy.
    Expert Opinion on Drug Delivery 08/2014;
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    ABSTRACT: Introduction: Transdermal drug delivery offers a number of advantages for the patient, not only due to its non-invasive and convenient nature, but also due to factors such as avoidance of first-pass metabolism and prevention of gastrointestinal degradation. It has been demonstrated that microneedles (MNs) can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum, and creating a pathway for drug permeation to the dermal tissue below. Areas covered: MNs have been extensively investigated for drug and vaccine delivery. The different types of MN arrays and their delivery capabilities are discussed in terms of drugs, including biopharmaceutics and vaccines. Patient usage and effects on the skin are also considered. Expert opinion: MN research and development is now at the stage where commercialisation is a viable possibility. There are a number of long-term safety questions relating to patient usage which will need to be addressed moving forward. Regulatory guidance is awaited to direct the scale-up of the manufacturing process alongside provision of clearer patient instruction for safe and effective use of MN devices.
    Expert Opinion on Drug Delivery 07/2014;
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    ABSTRACT: Background: Andrographolide (ADG) isolated from Andrographis paniculata exhibits anti-inflammatory and anticancer activities, but high hydrophobicity and poor bioavailability greatly restricts its clinical application. Objectives: In this study, ADG was encapsulated in a micelle formulation based on poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) amphiphilic triblock copolymers, in order to enhance the anticancer efficacy and bioavailability in vivo. Methods: The physicochemical properties of the ADG-loaded PLGA-PEG-PLGA micelles were investigated for encapsulation efficiency, particle size, zeta potential and critical micelle concentration. These micelles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle arrest and pro-apoptosis effects against human breast cancer MAD-MB-231 cells, cellular uptake and pharmacokinetics study in rat. Results: ADG-loaded PLGA-PEG-PLGA micelles had a high encapsulation and loading efficiency of about 92 and 8.4% (w/w), respectively, and a stable particle size of 124.3 ± 6.4 nm. In vitro cytotoxicity testing demonstrated that ADG-loaded PLGA-PEG-PLGA micelles exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and pro-apoptosis effects in MAD-MB-231 cells, which would be contributed to higher efficiency of cellular uptake and intracellular transport. Further, the plasma AUC(0 - ∞) and mean resident time of ADG-loaded PLGA-PEG-PLGA micelles were increased by 2.7- and 2.5-fold, respectively, when compared to the raw suspension. Conclusion: All of these investigations suggest that PLGA-PEG-PLGA micelles may be a potential drug delivery strategy for improving ADG bioavailability and efficacy in cancer therapy.
    Expert Opinion on Drug Delivery 06/2014;
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    ABSTRACT: Introduction: Airway inflammation and remodelling in asthma occur in the large airways and also in the small airways. The small airways are those < 2 mm in diameter and are significant sites of chronic asthmatic inflammation. It is important, therefore, to target the small as well as the large airways in any strategy for effective treatment of this disease. Areas covered: The present review deals with the recently developed fixed dose drug combination of beclometasone dipropionate/formoterol fumarate that emits extrafine particles when delivered from an innovative dry powder inhaler (DPI), NEXThaler®. The aim is to present the technical and clinical aspects of aerosolized drug delivery to the lungs. Expert opinion: The data show that the NEXThaler® DPI is an efficient device for the management of persistent asthma. The evaluation of the inhalation profiles through the NEXThaler® DPI demonstrates that device activation and consistent dose delivery occurs at patient achievable inhalation flow rates, and supports the broad utility of the NEXThaler® DPI in patients with asthma. Overall, all the effectiveness, efficiency and satisfaction outcomes demonstrate the NEXThaler® DPI is easy to use.
    Expert Opinion on Drug Delivery 06/2014;
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    ABSTRACT: Micromotors and nanomotors are an emerging research field that aims at achieving locomotion on the microscale for a variety of applications such as drug delivery, single cell manipulation, microsensors and lab-on-a-chip devices, just to point out a few. The enthusiastic development of hybrid micromotors harnessing biological power sources for physiologically compatible nano/microdevices has recently brought a lot of attention to the international research community that is looking for a solution for the actuation and locomotion on the microscale. This article describes the potential of sperm-driven micro-bio-robots in the biomedical field such as drug delivery or single cell manipulation. Herein, a specific potential of the sperm-driven micro-bio-robot is described that might have impact on the development of assisted reproductive technologies.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Objective: The aim of this study was to develop and optimize a transdermal gel formulation of valsartan using Box-Behnken design and to evaluate it for pharmacokinetic study. Methods: The independent variables were Carbopol 940 (X 1), PEG 400 (X 2) and ethanol (X 3) while valsartan flux (Y 1), T lag (Y 2) and gel viscosity (Y 3) were the dependent variables. Iso-eucalyptol was added in all gel formulations as permeation enhancer except for control gel. Results: It was observed that the permeation rate of valsartan significantly increased in direct proportion to the ethanol concentration, but significantly decreased in direct proportion to polymer concentration. Lag time and viscosity decreased in reverse proportion to ethanol concentration. The optimized valsartan gel formulation (VGF-OPT) yielded flux of 143.27 ± 7.11 µg/cm(2)/h and 27.55 ± 2.51 µg/cm(2)/h across rat and human cadaver skin, respectively. In vivo pharmacokinetic study of VGF-OPT-transdermal therapeutic system containing iso-eucalyptol showed a significant increase in the bioavailability (2.52 times) compared with oral formulation of valsartan by virtue of better permeation through Wistar rat skin. Conclusion: It was concluded that the developed transdermal gel accentuates the flux of valsartan and could be used as an antihypertensive dosage form for effective transdermal delivery of valsartan.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Introduction: Natural products have seen a wide range of acceptability for the prevention and treatment of diseases throughout history. Resveratrol, a member of the stilbene family, has been found to potentially exhibit anticancer, antiangiogenic, immunomodulatory and cardioprotective activities as well as being an antioxidant. This is in addition to its usefulness in the treatment of neurodegenerative disease, diabetes and cardiac ailments. Currently, various studies have revealed that resveratrol is a potential drug candidate with multi-spectrum therapeutic application. Areas covered: This review aims to describe the various studies supporting the wide range of pharmacological activities of resveratrol. In addition, it includes a section devoted to discussing the challenges associated with the drug and strategies to improve the properties of resveratrol such as solubility, stability and bioavailability. Expert opinion: Resveratrol demonstrated its ability to be a potential drug candidate for the treatment of different ailments due to its potent antioxidant properties. To improve the drug stability, increase the bioavailability and minimize side-effects of resveratrol, novel drug delivery systems have been formulated to bring this potential candidate to the first line of disease treatment.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Objectives: Drug diversion is a growing problem in numerous countries. Some laboratories have developed tamper-resistant formulations. The problem for healthcare authorities is now to assess new formulations developed to limit the risk of diversion for administration by another mode and intended mode. It would be helpful to have a pertinent panel of in vitro tests allowing assessment of how a formulation may be altered, both for healthcare authorities and for laboratories, so as to implement adequate sanitary measures. We designed a methodology/tool allowing assessment, in a standardized manner, of the formulation's resistance to drug diversion. We present the various steps leading to the construction of the scale and to its first use. Method: Creating a Steering Committee - Choosing assays or parameters - standardized by a monograph of the European Pharmacopoeia and pragmatic assays related to users' behaviors - for the assessment of formulation resistance to drug diversion. Designing a scale: i) applying all these tests to a panel of formulations; ii) applying a score by drug and by test; and iii) attribution of weighting per test and calculating the total score for a drug. Results: Eight tests or parameters and 14 drugs (diverted drugs and controls) were chosen. Buprenorphine Subutex® had the lowest score and flunitrazepam Rohypnol® the highest. Conclusions: Our tool allowed classification of the various drugs selected. This classification correlated with results of postmarketing authorization assessment. Rohypnol®, which was the object of many measures, including formulation changes, obtained the highest score in our study.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Background: Atazanavir (ATV) is a HIV protease inhibitor. Due to its intense lipophilicity, the oral delivery of ATV encounters several problems such as poor aqueous solubility, pH-dependent dissolution and rapid first-pass metabolism in liver by CYP3A5, which result in low and erratic bioavailability. Objective: The current study aimed to develop self-nanoemulsifying drug delivery systems (SNEDDS) using long-chain triglycerides of ATV in an attempt to circumvent such obstacles. Methods: Equilibrium solubility studies indicated the choice of Maisine 35-1 as lipid, and of Transcutol P and Span 20 as surfactants, for formulating the SNEDDS. Ternary phase diagrams were constructed to select the areas of nanoemulsions, and the amounts of lipid (X1) and surfactant (X2) as the critical factor variables. The SNEDDS were optimized (OPT) using 3(2) central composite design and the OPT formulation located using overlay plot. The pharmacokinetics and in situ single-pass intestinal perfusion studies of OPT formulation were investigated in Wistar rats. Results: OPT formulation indicated marked improvement in drug release profile vis-à-vis pure drug. Cloud point determination and accelerated stability studies ascertained the stability of OPT formulation. Augmentation in the values of Ka (1.96-fold) and AUC (2.57-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT formulation compared to pure drug. Successful establishment of in vitro/in vivo correlation Level A substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. Conclusion: The studies, therefore, indicate the successful formulation development of SNEDDS with distinctly improved bioavailability of ATV.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Intravitreal injection is one of the most common in-office procedures performed in ophthalmic practices. In teaching institutions such as the Veterans Affairs (VA) Hospitals, patient care is delivered by physicians-in-training, while mastering intravitreal injection technique. Infectious endophthalmitis and visual loss are the most feared complications of intravitreal injections, especially in the context of recent outbreaks caused by contaminated compounded medications. Ophthalmologists and ophthalmic educators increasingly face the dilemma of timing as well as balancing the risks and benefits of bilateral treatments required by many patients. In this editorial, we discuss published reports of bilateral injections, summarize our experience with bilateral intravitreal injections in a teaching setting at the Miami VA Hospital and list our recommendations for minimizing the risk of infectious endophthalmitis.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Introduction: Pharmaceutical research and development is increasingly focussed on biopharmaceuticals including peptide and protein drugs. Despite their growing importance and almost 100 years of research, the vast majority are still only available by injection. Oral bioavailabilities of peptide and protein drugs are very low mainly because of the stability and permeability barriers of the gastrointestinal (GI) tract. Areas covered: Data from studies of peptide/protein drug oral bioavailability, stability and permeability in the stomach, small intestine and large intestine have been compiled to make comparisons between the various regions of the GI tract and peptides/proteins with differing characteristics. Assessment of the oral formulation strategies that have progressed farthest in clinical trials has been conducted to identify which have the best potential for future success. Expert opinion: Oral delivery of peptides and small proteins is increasingly achieved by utilising formulations that combat the stability challenges of the GI tract and disrupt the intestinal cell membranes to enable absorption. However, oral bioavailabilities remain low and variable therefore high, potentially toxic doses of peptide/protein drugs are needed to elicit a therapeutic effect leading to high cost of the final product. There is very little research into larger proteins, making their oral delivery unlikely in the near future.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Introduction: The therapeutic effects of medicinal drugs not only depend on their properties, but also on effective transport to the target receptor. Here we highlight recent developments in this discipline and show applications of atomic force microscopy (AFM) that enable us to track the effects of drugs and the effectiveness of nanoparticle delivery at the single molecule level. Areas covered: Physiological AFM imaging enables visualization of topographical changes to cells as a result of drug exposure and allows observation of cellular responses that yield morphological changes. When we upgrade the regular measuring tip to a molecular biosensor, it enables investigation of functional changes at the molecular level via single molecule force spectroscopy. Expert opinion: Biosensing AFM techniques have generated powerful tools to monitor drug delivery in (living) cells. While technical developments in actual AFM methods have simplified measurements at relevant physiological conditions, understanding both the biological and technical background is still a crucial factor. However, due to its potential impact, we expect the number of application-based biosensing AFM techniques to further increase in the near future.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Introduction: The term Janus particles was used to describe particles that are the combination of two distinct sides with differences in chemical nature and/or polarity on each face. Due to the exponential growth of interest on multifunctional nanotechnologies, such anisotropic nanoparticles are promising tools in the field of drug delivery. Areas covered: The main preparation processes and the materials used have been described first. Then a specific focus has been done on therapeutic and/or diagnostic applications of Janus particles. Expert opinion: Janus particles are demonstrated as interesting objects with advanced properties that combine features and functionalities of different materials in one single unit. Due to their dual structure, Janus particles are promising candidates for a variety of high-quality applications dealing with drug delivery purposes. Still, the main challenges for the future lie in the development of the preparation of shape-controlled and nano-sized particles with large-scale production processes and approved pharmaceutical excipients.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Introduction: The design of new nanocarriers as a strategy for the delivery of anti-cancer drugs offers a potential platform to overcome some limitations of current clinical treatments and to achieve targeted release into tumour tissues. Cyclodextrin-based nanosponges are a novel nanosized delivery system composed of hyper-cross-linked cyclodextrins connected in a three-dimensional network. They form porous nanoparticles with sizes lower than 500 nm, spherical shape and negative surface charge. They show a good capacity for incorporating small molecules, macromolecules, ions and gases within their structure. Area covered: This review will describe some applications of cyclodextrin-based nanosponges as carriers for anticancer drugs. Recent smart nanosponges, able to be responsive to an external stimulus, will be also discussed. In vitro and in vivo experimental results, obtained with currently used molecules, such as paclitaxel, doxorubicin, 5-fluorourcil and tamoxifen, will be shown. Expert opinion: Cyclodextrin-based nanosponges can be considered a challenging technology for the development of innovative formulations, suitable for various administration routes for anti-cancer drugs.
    Expert Opinion on Drug Delivery 05/2014;
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    ABSTRACT: Introduction: This review deals with the use of serum albumin (SA) as a carrier for the selective delivery of drugs to liver cells. Areas covered: The synthesis and properties of the SA conjugates prepared to enhance the performance of the drugs used in the treatment of viral hepatitis, hepatocellular carcinoma (HCC), liver micrometastases and hepatic fibrosis are reported. Expert opinion: Studies in humans and laboratory animals demonstrated the capacity of SA conjugates to accomplish a liver targeting of the drugs, but at the same time underscored their limits and drawbacks, which can explain why to date these complexes did not reach a practical application. The major drawback is the need of administration by intravenous route, which prevents long-term daily treatments as required by some liver pathologies, such as chronic virus hepatitis and fibrosis. At present, only a conjugate carrying doxorubicin and addressed to the treatment of HCC showed in laboratory animals a solid potentiality to improve the value of the coupled drug. In the future, conjugation to SA could remain a successful strategy to permit the administration of drugs with rapid resolutive effects inside liver cells without causing severe extrahepatic adverse reactions.
    Expert Opinion on Drug Delivery 04/2014;