Application of TPGS in polymeric nanoparticulate drug delivery system

d-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) has great potential in pharmacology and nanotechnology. The present work investigated the molecular behaviour of TPGS at the air-water interface, its effect on a model bio-membrane composed of dipalmitoylphosphatidylcholine (DPPC) lipid monolayer, and the interaction between the TPGS coated nanoparticles with the lipid model membrane. Paclitaxel loaded polymeric nanoparticles with TPGS as surfactant stabiliser were fabricated and characterised in terms of their drug incorporation capability and release kinetics. The result showed that TPGS exhibited notable effect on the surface properties of air-water interface as well as the lipid monolayer. The inter-particle force and the interaction between nanoparticles and lipid monolayer varied with the surface substance. The penetration of various nanoparticles into the model membrane indicated that an optimal balance between hydrophilicity and hydrophobicity on nanoparticle surface is needed to achieve an effective cellular uptake of nanoparticles. The results also demonstrate that the drug incorporation capability and the release characteristics of drug-loaded nanoparticles can be influenced by surfactant stabiliser.     

Electrophoretic separation and characterisation of gliadin fractions from isolates and nanoparticulate drug delivery systems

Summary Gliadin is a group of polymorphic proteins that are commonly used for the preparation of many pharmaceutical and cosmetic products. The aim of this study was to develop an analytical HPCE procedure for the identification and quantification of gliadin samples. For this purpose, the HPCE buffer composition were optimised to improve the resolution of separations. There-fore, several buffer modifiers were tested for use with 50 mM phosphate buffer in HPCE separations. Twenty percent acetonitrile and 0.05% hydroxypropylmethyl-cellulose provided optimal resolution while maintaining excellent reproducibility. In conclusion, this method can be successfully applied to the elucidation of the different gliadin fractions in protein isolates and nanoparticulate dosage forms.     

Multiparticulate chitosan-dispersed system for drug delivery

A multiparticulate chitosan-dispersed system (CDS), which is composed of the drug reservoir and the drug release-regulating layer, was developed for drug delivery. The drug release-regulating layer is a mixture of water-insoluble polymer and chitosan powder. The drug is released from CDS pellets in all regions of the gastrointestinal tract (from the stomach to the colon). CDS pellets containing chitosan powder were designed to dissolve chitosan powder partly in the release-regulating layer in the stomach and release part of drug. After passing through the stomach, the drug is released from CDS pellets at a constant speed in the small intestine. In the large intestine, CDS pellets were designed to disintegrate the remaining chitosan powder at an accelerated speed and the remaining drug in CDS pellets is released. The drug release rate can be controlled with the thickness of the chitosan-dispersed water-insoluble layer. Furthermore, for colon-specific drug delivery, an additional outer enteric coating is necessary to prevent drug release from CDS pellets in the stomach, because the chitosan-dispersed water-insoluble layer dissolves gradually under acidic conditions. The resulting enteric-coated CDS (E-CDS) pellets were found to permit colon-specific drug delivery. In this study, the multiparticulate CDS was adopted not only for colon-specific drug delivery but also for sustained drug release.     

A low-voltage electrokinetic nanochannel drug delivery system

Recent work has elucidated the potential of important new therapeutic paradigms, including metronomic delivery and chronotherapy, in which the precise timing and location of therapeutic administration has a significant impact on efficacy and toxicity. New drug delivery architectures are needed to not only release drug continuously at precise rates, but also synchronize their release with circadian cycles. We present an actively controlled nanofluidic membrane that exploits electrophoresis to control the magnitude, duration, and timing of drug release. The membrane, produced using high precision silicon fabrication techniques, has platinum electrodes integrated at the inlet and outlet that allow both amplification and reversal of analyte delivery with low applied voltage (at or below 2 VDC). Device operation was demonstrated with solutions of both fluorescein isothiocyanate conjugated bovine serum albumin and lysozyme using fluorescence spectroscopy, fluorescence microscopy, and a lysozyme specific bio-assay and has been characterized for long-term molecular release and release reversibility. Through a combination of theoretical and experimental analysis, the relative contributions of electrophoresis and electroosmosis have been investigated. The membrane's clinically relevant electrophoretic release rate at 2 VDC exceeds the passive release by nearly one order of magnitude, demonstrating the potential to realize the therapeutic paradigm goal.     

A new oral microsphere drug delivery system

A new oral proteinoid microsphere drug delivery system is discussed with respect to its unique dependence on pH. Extensive evidence indicate that this technique not only can be used to deliver the protein and polar macromolecular drugs which are currently administered via injection, but also can be used to administer antigens and vaccines. Future work has been proposed to study the physical interaction of specific drugs with specifically designed oligopeptides structures.     

Novel drug delivery system by chitin derivative

A porous chitin foam was regenerated from chitin dope in calcium chloride dihydrate saturated methanol. The porous chitin foam was shown to have cationic property, because chitin foam tended to adsorb anionic dyes through ionic binding and hydrophobic interaction. A pendant type of polymeric drug was prepared applying peptide spacer composed of phenylalanine at amino end and two step hydrolyses of polymeric drug were shown to release active drug at the final step using lysozyme and chymotrypsin in vitro.     

普鲁兰多糖在药物释放系统中的应用

本综述重点介绍了近年来普鲁兰多糖作为药物释放系统载体材料的研究进展及其在药物释放系统中的应用情况。     

Chitosan/cyclodextrin nanoparticles as drug delivery system

One of the most attractive areas of research in drug delivery is the design of nanomedicines consisting of nanosystems that are able to deliver drugs to the right place, at appropriate time. Natural polysaccharides, due to their outstanding merits, have received more and more attention in the field of drug delivery systems. In particular, polysaccharides seem to be the most promising materials in the preparation of nanometric carriers. The main goal of the present study was to investigate the potential of a recent generation of hybrid polysaccharide nanocarriers, composed of chitosan (CS) and an anionic cyclodextrin, carboxymethyl-β-cyclodextrin (CM-β-CD), for the encapsulation of a model drug, sulindac. CS and CM-β-CD were processed to nanoparticles (NPs) via the ionotropic gelation technique. The stoichiometric ratio between these two polymers was found to influence particle size and zeta potential. Decreasing CS:CM-β-CD ratio led to an increase in particle size and decrease in zeta potential. DSC and FTIR analyses confirmed formation of NPs and encapsulation of sulindac inside them. Release profiles indicate a continuous release of the drug throughout 24?h. However, the rate of release was more rapid during the first hours; about 55–90% of the drug being released after 3?h.     

Subcutaneous hydrogel reservoir system for controlled drug delivery

Hydro Med Sciences has developed a subcutaneous reservoir hydrogel implant capable of long term delivery of predetermined doses of various active compounds. The implant is a small-diameter, thin-walled cylindrical capsule containing a therapeutic agent. The hydrogels used for this application were Hydron* type copolymers of 2-hydroxyethyl methacrylate (HEMA). These non-erodible hydrogels are known to be biocompatible, swell reversibly in an aqueous environment, resist biodegradation and do not support microbial growth.     

pH-sensitive supramolecular copolydendrimers,new anticancer drug delivery system

In this work, new class of supramolecular copolydendrimers (SCDs) consisting of polyamidoamines (PAMAMs) and polyglycerol were synthesized through host-guest interactions. SCDs were able to encapsulate, transport, and release doxorubicin (DOX) efficiently. Host-guest interactions between PAMAM and polyglycerol was depended on pH so that aqueous solutions of SCDs and SCDs-based drug delivery systems were stable at room temperature and pH?=?7.4, but their building blocks were separated in lower pHs(     

Preparation of floating drug delivery system by plasma technique

A novel intragastric floating drug delivery system (FDDS) has been prepared by pulsed plasma-irradiation on the double-compressed tablet of 5-Fluorouracil (5-FU) as a core material with outer layer composed of a 68/17/15 weight ratio of Povidone (PVP), Eudragit RL (E-RL) and NaHCO3. The plasma heat flux caused the thermal decomposition of NaHCO3 to generate carbon dioxide and the resultant gases were trapped in bulk phase of outer layer, so that the tablets turned to have a lower density than the gastric contents and remained buoyant in simulated gastric fluid for a prolonged period of time. In addition, the release of 5-FU from the tablet is sustained by occurrence of plasma-induced crosslink reaction on the outer layer of tablet and the release rate of 5-FU can be well controlled by plasma operational conditions.     

Dual drug delivery system with flexible and controllable drug ratios for synergistic chemotherapy

Determination of whether multidrug nanocarriers can deliver and release loaded drugs at a predefined synergistic ratio to target cancer cells is crucial. Although there are many successful applications for delivery of multiple drugs, most current carriers are unable to achieve coordinated loading and release, leading to a drug release ratio that disagrees with the predefined loading ratio.In this work, a simple dual-drug delivery system with a flexible and controllable drug release ratio was constructed to deliver two anticancer drugs, doxorubicin(DOX) and curcumin(CUR). The drug ratio of DOX and CUR can be easily tuned for an enhanced synergistic effect, and the drugs can be released at predesigned ratios due to synchronous drug activation and nanoparticle collapse. Drug release at predefined ratios for synergistic anticancer therapy was demonstrated via in vitro and in vivo experiments. Therefore, the dual drug delivery system developed here provides a simple and efficient strategy for combination chemotherapy.     

Numerical study of a drug release profile in the transdermal drug delivery system

Drug release by diffusion from an unstressed thin polymer film with a dissolved crystallizable component was simulated using a kinetic Monte Carlo model. This model was used previously to study Ostwald ripening in a high crystallizable component regime and was shown to correctly simulate solvation, diffusion, and precipitation. In this study, the same model with modifications was applied to the drug transportation and release in the low concentration regime of interest to the transdermal drug delivery system (TDS) community. We demonstrate the model's utility by simulating diffusion, crystal precipitation, growth and shrinkage during storage, and drug release from the thin TDS to a surface under different conditions. The simulation results provide a first approximation for the drug release profile occurring from TDS to skin. It has been reported that growth of drug crystals in TDS occurs mainly in the middle third of the polymer layer at relatively higher temperatures. The results from the simulations showed that the release rate and concentration profile of a TDS depend on the dissolution process of the crystal. At low storage temperature, the drug precipitates to form small evenly distributed crystals throughout the thickness of the TDS patch. The release rate of these small, evenly distributed crystals most closely matched that of a completely dissolved drug.     

Chitosan modified with terephthaloyl diazide as a drug delivery system

Russian Chemical Bulletin - pH- and thermo-sensitive hydrogels based on chitosan cross-linked with terephthaloyl diazide were synthesized. A new formulation of the polysaccharide modified with...     

Green amorphous nanoplex as a new supersaturating drug delivery system

The nanoscale formulation of amorphous drugs represents a highly viable supersaturating drug-delivery system for enhancing the bioavailability of poorly soluble drugs. Herein we present a new formulation of a nanoscale amorphous drug in the form of a drug-polyelectrolyte nanoparticle complex (or nanoplex), where the nanoplex is held together by the combination of a drug-polyelectrolyte electrostatic interaction and an interdrug hydrophobic interaction. The nanoplex is prepared by a truly simple, green process that involves the ambient mixing of drug and polyelectrolyte (PE) solutions in the presence of salt. Nanoplexes of poorly soluble acidic (i.e., ibuprofen and curcumin) and basic (i.e., ciprofloxacin) drugs are successfully prepared using biocompatible poly(allylamine hydrochloride) and dextran sulfate as the PE, respectively. The roles of salt, drug, and PE in nanoplex formation are examined from ternary phase diagrams of the drug-PE complex, from which the importance of the drug's charge density and hydrophobicity, as well as the PE ionization at different pH values, is recognized. Under the optimal conditions, the three nanoplexes exhibit high drug loadings of ~80-85% owing to the high drug complexation efficiency (~90-96%), which is achieved by keeping the feed charge ratio of the drug to PE below unity (i.e., excess PE). The nanoplex sizes are ~300-500 nm depending on the drug hydrophobicity. The nanoplex powders remain amorphous after 1 month of storage, indicating the high stability owed to the PE's high glass-transition temperature. FT-IR analysis shows that functional groups of the drug are conserved upon complexation. The nanoplexes are capable of generating prolonged supersaturation upon dissolution with precipitation inhibitors. The supersaturation level depends on the saturation solubility of the native drugs, where the lower the saturation solubility, the higher the supersaturation level. The solubility of curcumin as the least-soluble drug is magnified 9-fold upon its transformation to the nanoplex, and the supersaturated condition is maintained for 5 h.     

Design and optimization of a new self-nanoemulsifying drug delivery system

To improve the dissolution rate of ibuprofen, a model poorly water soluble drug, self-nanoemulsifying drug delivery systems (SNEDDS) were developed. Various surfactants and oils were screened as candidates for SNEDDS on the basis of droplet size of the resulting emulsions. The influence of the constituent structure, concentration and the composition of SNEDDS formulations, and the emulsifier HLB value, on the properties of the resulting emulsions was systematically investigated. Several SNEDDS formulations were employed to study the relationship between the emulsion droplet size and the dissolution rate of ibuprofen. The dissolution rate was accelerated by decreasing the nanoemulsion droplet size, and was significantly faster than that from a conventional tablet. The optimal SNEDDS formulation had a mean nanoemulsion droplet diameters of 58 nm in phosphate buffer, pH 6.8 (simulated intestinal fluid), and released ibuprofen more than 95% within 30 min. Therefore, these novel SNEDDS carriers appear to be useful for controlling the release rate of poorly water soluble drugs.     

Chitosan nanoparticles: a promising system in novel drug delivery

The ability of nanoparticles to manipulate the molecules and their structures has revolutionized the conventional drug delivery system. The chitosan nanoparticles, because of their biodegradability, biocompatibility, better stability, low toxicity, simple and mild preparation methods, offer a valuable tool to novel drug delivery systems in the present scenario. Besides ionotropic gelation method, other methods such as microemulsion method, emulsification solvent diffusion method, polyelectrolyte complex method, emulsification cross-linking method, complex coacervation method and solvent evaporation method are also in use. The chitosan nanoparticles have also been reported to have key applications in parentral drug delivery, per-oral administration of drugs, in non-viral gene delivery, in vaccine delivery, in ocular drug delivery, in electrodeposition, in brain targeting drug delivery, in stability improvement, in mucosal drug delivery in controlled drug delivery of drugs, in tissue engineering and in the effective delivery of insulin. The present review describes origin and properties of chitosan and its nanoparticles along with the different methods of its preparation and the various areas of novel drug delivery where it has got its application.     

Iontophoretic transdermal drug delivery system using a conducting polymeric membrane

This work investigated the application of a porous polyaniline (PANi) membrane as a conducting polymeric membrane as well as an electrode in an iontophoretic transdermal drug delivery (TDD) system. Model drugs studied were: caffeine (MW: 194.2), lidocaine HCl (MW: 270.8) and doxycycline HCl (MW: 480.1). The PANi membrane was first tested as a simple membrane between the donor and receptor solutions; it provided satisfactory permeation profiles; the observed flux values were well described by a simplified mass transport model. A mouse skin was then mounted beneath the PANi film; such a composite system also presented satisfactory permeation profiles. Iontophoretic TDD experiments were next performed using both Ag|AgCl electrodes and PANi|AgCl electrodes for comparison; a PANi anode replaced the Ag anode in the last set. For doxycycline HCl, the flux and the 24-h accumulation from the PANi|AgCl set were 94.4 ± 81.2 μg/cm² h and 2760 ± 3980 μg/cm², respectively; those from the Ag|AgCl set were zero. For lidocaine HCl, the flux and 10-h accumulation from the PANi|AgCl set were, respectively, 43 ± 15 μg/cm² h and 392 ± 130 μg/cm²; the corresponding values from the Ag|AgCl set were 48 ± 20 μg/cm² h and 348 ± 78 μg/cm². Porous polyaniline membrane appears to be capable of replacing the Ag part of Ag|AgCl electrode system; further such a membrane can exercise additional control over agent transport rate. Aqueous-organic partitioning system through the porous membrane of PANi was tested with this novel technique as well. Because of the rather low porosity of the synthesized PANi film, such a system did not yield a high permeation rate.     

A dual-responsive hyaluronic acid nanocomposite hydrogel drug delivery system for overcoming multiple drug resistance

Chemotherapy is restricted by efficient drug outflow due to the multiple drug resistance (MDR) in heterogenous nature of tumor. Herein, we present a dual-responsive hyaluronic acid (HA) nanocomposite hydrogel that can not only response to the tumor microenvironment but also enhance chemotherapy. This HA hydrogel consists of a core-shell SiO₂ (GOD@SiO₂-Arg) and mesoporous silica nanoparticles (MSNs) with doxorubicin (DOX) as the cargo (DOX@MSN). It could rapidly release the GOD@SiO₂-Arg nanoparticles at the low pH tumor-specific environment due to the cleavage of imine bond. GOD@SiO₂-Arg activated by over-expressed glutathione (GSH) in tumor cells releases GOD due to the cleavage of disulfide bonds, which could oxidize glucose to produce hydrogen peroxide (H₂O₂) for in situ NO generation via reaction between Arg and H₂O₂. The validity of this study might provide a method to modulate the tumor microenvironment for enhancing chemotherapy.     

Determination of oligonucleotide ISIS 2922 in nanoparticulate delivery systems by capillary zone electrophoresis

ISIS 2922 is an antisense oligonucleotide with antiviral activity against cytomegalovirus. However, its rapid degradation in biological fluids and its low capacity for diffusion across cell membranes limit its therapeutical use. One possibility to overcome these drawbacks consists of using nanoparticles as drug carriers. The aim of this study was to develop an analytical method for determining the amount of ISIS 2922 loaded into albumin nanoparticles. For this purpose, capillary zone electrophoresis (CZE) was performed on a fused-silica capillary filled with borate buffer (12.5 mM, pH 9.5). Paracetamol was used as an internal standard and a diode-array detection system was set at 270 nm. Under these conditions, the limit of quantitation of ISIS 2922 was 1.27 microg and the precision and accuracy of the method did not exceed 7%. Moreover, the use of paracetamol as internal standard and the quantification by means of a 'corrected area' procedure enabled us to reduce the peak variability and accurately determine the amount of oligonucleotide loaded in the albumin nanoparticles. In summary, this assay is a selective and sensitive CZE method for the accurate quantitation of ISIS 2922 oligonucleotide in albumin nanoparticles.