1223 POSTER Enhanced Cellular Delivery of Idarubicin by Surface Modification of Propyl Starch Nanoparticles Employing Pteroic Acid Conjugated Polyvinyl Alcohol
Department of Biopharmaceutics and Pharmaceutical Technology, Campus A4 1, Saarland, University, Saarbrücken, Germany. International Journal of Pharmaceutics
(Impact Factor: 3.65).
08/2011; 420(1):147-55. DOI: 10.1016/j.ijpharm.2011.08.030
Enhanced intracellular internalization of the anti-cancer active idarubicin (IDA) was achieved through appropriate surface modification of IDA loaded propyl starch nanoparticles. This was conducted by synthesizing pteroic acid modified polyvinyl alcohol (ptPVA) and employing this stabilizer for formulating the said nanoparticles. Pteroic acid attached at the nanoparticles improved the surface protein adsorption of the nanoparticle, a condition which the nanoparticles would largely experience in vitro and in vivo and hence improve their cellular internalization. Spherical, homogenous IDA nanoparticles (214 ± 5 nm) with surface modified by ptPVA were formulated using the solvent emulsification-diffusion technique. The encapsulation efficiency and drug loading amounted around 85%. In vitro release studies indicated a controlled release of IDA. Safety and efficacy of the nanoparticles was confirmed by suitable cellular cytotoxicity assays. Protein binding studies indicated a higher adsorption of the model protein on nanoparticles formulated with ptPVA as compared to PVA. Cellular uptake studies by confocal laser scanning microscopy revealed a higher cellular uptake of ptPVA stabilized nanoparticles thus confirming the proposed hypothesis of higher protein adsorption being responsible for higher cellular internalization.
Available from: David Julian Mcclements
- "Hydrophobic starch derivatives have therefore been developed to overcome this drawback . Dialdehyde starch (Yu, Xiao, Tong, Chen, & Liu, 2007) and propyl starch (Jain et al., 2011; Santander- Ortega et al., 2010) nanoparticles have been fabricated for encapsulation and delivery of lipophilic pharmaceutical agents. Octenyl Succinic Anhydride (OSA) modified starches have also been used to encapsulate food and flavor ingredients (Qi & Xu, 1999). "
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ABSTRACT: Natural and modified polysaccharides are promising vehicles for nano- and micro-encapsulation of active food ingredients. This article reviews the state of the art of carbohydrate-based delivery systems for utilization in the food, pharmaceutical and other industries. Initially, an overview of the different kinds of carbohydrates used to assemble delivery systems is given, including starch, cellulose, pectin, guar gum, chitosan, alginate, dextrin, cyclodextrins, new sources of native gums, and their combinations and chemically modified forms. Their molecular and physicochemical properties, functional performance, and advantages and disadvantages for encapsulation are given. Various approaches for fabrication of carbohydrate-based delivery systems are then discussed, including coacervation, spray drying, electrospinning, electrospray, supercritical fluid, emulsion-diffusion, reverse micelle, emulsion-droplet coalescence, emulsification/solvent evaporation, salting-out, ultrasonication and high pressure homogenization. The biological fate of carbohydrate nanocarriers during digestion, absorption, metabolism and excretion are discussed, and some notes about their bioavailability and potential toxicity are provided. Finally, the functional performances of different carbohydrate-based delivery systems are discussed, and future developments are highlighted.
Available from: Vahid Hosseini
- "Apoptosis induction is one of the mechanisms which has attracted researchers' attention for fighting against cancer . Doxorubicin , daunorubicin , idarubicin , bleomycin , mitomycin C , cisplatin , plicamycin , and carmustine  are of the well-known apoptogenic agents; although in order to serve them in targeted drug delivery system, appropriate drug carriers should be employed. Such carriers are aimed to facilitate drug delivery procedure and avoid problems like bioavailability and normal tissue toxicity. "
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ABSTRACT: Employment of nanovehicular system for delivering apoptogenic agent to cancer cells for inducing apoptosis has widely been investigated. Loading efficacy and controlled release of the agents are of the inseparable obstacles that hamper the efforts in reaching an efficacious targeted cancer therapy method. When the carrier itself is apoptogenic, then there is no need to load the carrier with apoptogenic agent and just delivering of the particle to the specific location matters. Hence, we hypothesize that amorphous calcium phosphate nanoparticle (ACPN) is a potent candidate for apoptosis induction, although encapsulation in liposome shell, and surface decoration with targeting ligand (TL), and cell-penetrating peptide (CPP) plays a pivotal role in the employment of this agent. It is well understood that elevation in cytosolic Ca2+ ([Ca2+]c) would result in the induction of apoptosis. ACPN has the potential to cause imbalance in this medium by elevating [Ca2+]c. Owning to the fact that the nanoparticles should be delivered into cytosol, it is necessary to trap them in a liposomal shell for evading endocytosis. It was demonstrated that employment of the trans-activator of transcription (TAT) as CPP eminently enhances the efficacy of endosomal escape; therefore, the platform is designed in a way that TAT is positioned on the surface of the liposome. Due to the fact that the apoptosis should be induced in sole cancer cells, Folate as TL is also attached on the surface of the liposome. This hypothesis heralds the new generation of chemotherapeutic agents and platforms which could have less side effect than the most common ones, in addition to other advantages they have.
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ABSTRACT: The kinetics of in vitro drug release from nanoparticulate systems is extensive, though uncritically, being studied by dialysis. Evaluating the actual relevance of dialysis data to drug release was the purpose of this study. Diclofenac- or ofloxacin-loaded chitosan nanoparticles crosslinked with tripolyphosphate were prepared and characterized. With each drug, dynamic dialysis was applied to nanoparticle dispersion, solution containing dissolved chitosan·HCl, and solution of plain drug. Drug kinetics in receiving phase (KRP), nanoparticle matrix (KNM) and nanoparticle dispersion medium (KDM) were determined. Release of each drug from nanoparticles was also assessed by ultracentrifugation. Although KRP data may be interpreted in terms of sustained release from nanoparticles, KNM and KDM data show that, with both drugs, the process was in fact controlled by permeation across dialysis membrane. Analysis of KRP data reveals a reversible interaction of diclofenac with dispersed nanoparticle surface, similar to the interaction of this drug with dissolved chitosan·HCl. No such interactions are noticed with ofloxacin. The results from the ultracentrifugation method agree with the above interpretation of dialysis data. This case study shows that dialysis data from a nanoparticle dispersion is not necessarily descriptive of sustained-release from nanoparticles, hence, if interpreted uncritically, it may be misleading.
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