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.     

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.     

Oxaliplatin preformulation studies for the development of innovative topical drug delivery systems

Journal of Thermal Analysis and Calorimetry - The objectives of this study were to verify the viability of the photoinitiating system using curcumin as a photoinitiator and glycerol as a...     

Liposaccharide-based nanoparticulate drug delivery system

A series of anionic liposaccharide derivatives were synthesized in order to develop a system, which would have the capacity to act as an absorption enhancer and to improve oral bioavailability of drugs. The addition of a liposaccharide to a drug enhances drug stability against enzymatic degradation, while the lipophilicity can be controlled by variation of the lipid side chain. All liposaccharide derivatives were purified and fully characterized by nuclear magnetic resonance and high-resolution mass spectrometry. The thermodynamic profiles, critical aggregation concentrations and size of the synthesized liposaccharides were determined by isothermal titration microcalorimetry, transmission electron microscopy and dynamic light scattering. These liposaccharides formed nanoparticles with sizes below 100 nm.     

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.     

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.     

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。     

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.     

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 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.     

Fabrication and characterization of boric acid-crosslinked ethyl cellulose and polyvinyl alcohol films as potential drug release systems for topical drug delivery

In this study, boric acid (BA) is employed as a crosslinking agent to improve the characteristics of two commonly used polymeric films, ethyl cellulose (EC) and polyvinyl alcohol (PVA), for topical drug delivery applications. The developed films are characterized by FTIR spectroscopy and SEM analysis. The results show that the surfaces of the prepared films are even and transparent, except for the BA-modified EC sample. The initial cumulative release for erythromycin (EM) is found to be 0.30 and 0.36 mg/mL for EC and PVA films, which drops to 0.25 and 0.20 mg/mL after BA crosslinking, respectively, after 1 h at 25 °C. Further, the developed formulations are stable for 75 days. Also, the antibacterial activity of the developed formulations is investigated against S. aureus (ATCC® 25923™ and ATCC® 29213™). The obtained data confirm that the application of BA as the crosslinking agent extends the release of EM from EC and PVA polymeric films. The findings of this study suggest that BA-crosslinked EC and PVA films are promising carriers for controlled topical drug delivery applications.     

pH-enzyme di-dependent chronotherapeutic drug delivery system of theophylline for nocturnal asthma

The purpose of this research work was to develop and evaluate a chronotherapeutic based colon-targeted drug delivery system of theophylline (THEO) exploiting pH-enzyme sensitive property for the prevention of episodic attack of asthma in early morning. Guar gum microspheres of theophylline were prepared by emulsification technique. Coating of microspheres was performed using solvent evaporation method with pH sensitive Eudragit(?) polymers. The particle size and surface morphology, entrapment efficiency and degree of swelling of microspheres were examined. The in vitro drug release studies were performed in pH progression medium and also in the presence of 2% rat caecal content. Theophylline was efficiently microencapsulated in guar gum microspheres at different polymer concentrations (1-4%). Fourier transform infrared (FT-IR)-spectroscopy confirmed the intermolecular interactions between guar gum and glutaraldehyde. Coating of guar gum microspheres by Eudragit led to decelerate the in vitro drug release of THEO. Moreover in vitro drug release studies also performed with 2% rat caecal content showed marked increment in drug release. The controlled release of THEO after a lag time was achieved with developed formulation for chronotherapeutic delivery. The pH dependent solubility behavior of Eudragit and gelling properties of guar gum are found to be responsible for delaying the release.     

Modified MCM-41 as a drug delivery system for acetylsalicylic acid

The modification of prepared MCM-41 by different groups (amino, chloro and oxo) was studied. Prepared materials were treated by acetylsalicylic acid and hybrid materials were characterized, compared from the point of view of immobilized amount of active substance. The highest amount of acetylsalicylic acid was detected using methyl-tert- butyl ether as a solvent and MCM-41 without modification after 1 h (0.35 g per 1 g of the support) or MCM modified by amino group after 5 h (0.37 g per 1 g of the support) as a support. Using amino modified MCM, the longer treatment by acetylsalicylic acid converged to the equilibrium and after 24 h the immobilized amount was 0.3 g per 1 g. A dissolution in vitro study was carried out, comparing the stability of formed interactions. The slowest dissolution was detected using non-modified MCM-41 and oxo modified material.     

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.     

Biosensing and drug delivery by polypyrrole

Conducting polypyrrole is a biological compatible polymer matrix wherein number of drugs and enzymes can be incorporated by way of doping. The polypyrrole, which is obtained as freestanding film by electrochemical polymerization, has gained tremendous recognition as sophisticated electronic measuring device in the field of sensors and drug delivery. In drug delivery the reversing of the potential 100% of the drug can be released and is highly efficient as a biosensor in presence of an enzyme. In this review we discuss the applications of conducting polypyrrole as biosensor for some biomolecules and drug delivery systems.     

Biodegradable polyphosphazenes for drug delivery

Polyphosphazene derivatives having amino acid ester side groups were prepared by reaction of poly(dichlorophosphazene) with ethyl esters of amino acids. The in vitro degradation studies demonstrated that the rate of degradation depends on the nature of the amino acids. Introducing small amounts of hydrolytically sensitive groups such as depsipeptide ester or hydrolysis-catalysing moieties, such as histidine ethyl ester co-substituents, resulted in an increase of the degradation. The rate of hydrolytic degradation of the polyphosphazene material could be controlled by the content of the hydrolytically sensitive side groups or by blending hydrolysis-sensitive polymers with more stable derivatives. The results obtained from the in vivo implantation of biodegradable polyphosphazenes in mice indicate that the materials are very well tolerated by the animal body. Biodegradable polyphosphazenes have been used as matrix for the design of drug delivery systems. The rate of the in vitro release of mitomycin C from biodegradable polyphosphazenes can be controlled by changing the chemical composition of the polymer or by blending polymers of different chemical compositions.     

Mesoporous materials for drug delivery

Research on mesoporous materials for biomedical purposes has experienced an outstanding increase during recent years. Since 2001, when MCM-41 was first proposed as drug-delivery system, silica-based materials, such as SBA-15 or MCM-48, and some metal-organic frameworks have been discussed as drug carriers and controlled-release systems. Mesoporous materials are intended for both systemic-delivery systems and implantable local-delivery devices. The latter application provides very promising possibilities in the field of bone-tissue repair because of the excellent behavior of these materials as bioceramics. This Minireview deals with the advances in this field by the control of the textural parameters, surface functionalization, and the synthesis of sophisticated stimuli-response systems.     

Polymeric conjugates for drug delivery

The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer-drug conjugates with a wide variety of architectures and chemical properties. Whereas traditional non-degradable polymeric carriers such as poly(ethylene glycol) (PEG) and N-(2-hydroxypropyl methacrylamide) (HPMA) copolymers have been translated to use in the clinic, functionalized polymer-drug conjugates are increasingly being utilized to obtain biodegradable, stimuli-sensitive, and targeted systems in an attempt to further enhance localized drug delivery and ease of elimination. In addition, the study of conjugates bearing both therapeutic and diagnostic agents has resulted in multifunctional carriers with the potential to both "see and treat" patients. In this paper, the rational design of polymer-drug conjugates will be discussed followed by a review of different classes of conjugates currently under investigation. The design and chemistry used for the synthesis of various conjugates will be presented with additional comments on their potential applications and current developmental status.