Thermally reversible xyloglucan gels as vehicles for nasal drug delivery

The aim of this study was to investigate the potential application of thermosensitive gels formed by a xyloglucan polysaccharide derived from tamarind seed for nasal drug delivery. Xyloglucan that had been partially degraded by β-galactosidase to eliminate 45% of galactose residues formed gels at concentrations of 2.5% w/w at gelation temperatures decreasing over the range 27-28°C. The in vitro release of ondansetron hydrochloride from the enzyme-degraded xyloglucan gels followed higuchi kinetics over a period of 5?h at 34°C by anomalous transport mechanism. The ex vivo permeation of ondansetron hydrochloride from the gels was sustained. Histological examination of nasal mucosa following a single administration of the gels showed no evidence of mucosal damage. Finally, the bioavailability study in rabbits revealed that the absolute bioavailability of ondansetron hydrochloride was significantly increased from 28.64% in the case of the oral drug solution to 52.79% in the case of the nasal in situ gel. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for nasal delivery of drugs.     

Thermally reversible xyloglucan gels as vehicles for oral drug delivery.

The potential, as sustained release vehicles, of gels formed in situ following the oral administration of dilute aqueous solutions of a xyloglucan polysaccharide derived from tamarind seed has been assessed by in vitro and in vivo studies. Aqueous solutions of xyloglucan that had been partially degraded by beta-galactosidase to eliminate 44% of galactose residues formed rigid gels at concentrations of 1.0 and 1.5% w/w at 37 degrees C. The in vitro release of indomethacin and diltiazem from the enzyme-degraded xyloglucan gels followed root-time kinetics over a period of 5 h at 37 degrees C at pH 6.8. Plasma concentrations of indomethacin and diltiazem, after oral administration to rats of chilled 1% w/w aqueous solutions of the enzyme-degraded xyloglucan containing dissolved drug, and a suspension of indomethacin of the same concentration were compared. Constant indomethacin plasma concentrations were noted from both formulations after 2 h and were maintained over a period of at least 7 h. Bioavailability of indomethacin from xyloglucan gels formed in situ was increased approximately threefold compared with that from the suspension. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for oral delivery of drugs. Copyright     

鼻用原位凝胶给药系统中药物吸收的影响因素与改进措施

药物的吸收主要是由药物的理化性质、剂型以及给药途径所决定的。原位凝胶是指在生理条件刺激下能发生分散状态或构象的可逆变化、完成溶液与凝胶间相互转变的新剂型。原位凝胶经鼻腔给药,既避免了药物的胃肠首过效应,又因其能延长药物在给药部位滞留时间,从而避免药物被鼻纤毛快速清除。本文通过系统查阅近年国内外鼻用原位凝胶给药系统的相关文献,就鼻腔的生理特点、药物理化性质与原位凝胶的制剂处方等影响其药物吸收的主要因素及改进措施,进行分析、整理和归纳,旨在为鼻用原位凝胶给药系统的设计与质量控制提供参考。     

Assessment of polysaccharide gels as drug delivery vehicles

A range of cross-linked polysaccharide gels were prepared from bacterial sodium hyaluronate (HANa) and dextran using diethylenetriaminepentaacetic acid dianhydride (DTPA) as the cross-linking agent. The physical characteristics of the gels were assessed using a Ferranti-Shirley cone and plate viscometer, a TA-XT2 Universal Texture Analyser and FT-IR spectrometry. FT-IR demonstrated a concentration-dependent incorporation of DTPA to form gels from either polysaccharide with varying properties. The gels exhibited an increase in viscosity and maximal compression force with increasing cross-linking. Dextran gels were stronger and of greater viscosity than comparable HANa gels. The gels are being investigated as potential drug delivery vehicles for parenteral depot preparations.     

Drug release from xyloglucan beads coated with Eudragit for oral drug delivery

Xyloglucan (XG), which exhibits thermal sol to gel transition, non-toxicity, and low gelation concentration, is of interest in the development of sustained release carriers for drug delivery. Drug-loaded XG beads were prepared by extruding dropwise a dispersion of indomethacin in aqueous XG solution (2 wt.-%) through a syringe into corn oil. Enteric coating of XG bead was performed using Eudragit L 100 to improve the stability of XG bead in gastrointestinal (GI) track and to achieve gastroresistant drug release. Release behavior of indomethacin from XG beads in vitro was investigated as a function of loading content of drug, pH of release medium, and concentration of coating agent. Adhesive force of XG was also measured using the tensile test. Uniform-sized spherical beads with particle diameters ranging from 692 +/- 30 to 819 +/- 50 microm were obtained. The effect of drug content on the release of indomethacin from XG beads depended on the medium pH. Release of indomethacin from XG beads was retarded by coating with Eudragit and increased rapidly with the change in medium pH from 1.2 to 7.4. Adhesive force of XG was stronger than that of Carbopol 943 P, a well-known commercial mucoadhesive polymer, in wet state. Results indicate the enteric-coated XG beads may be suitable as a carrier for oral drug delivery of irritant drug in the stomach.     

Smart thermosensitive chitosan hydrogel for nasal delivery of ibuprofen to treat neurological disorders

Background: The in-situ gelation of thermosensitive nasal formulations with desirable spray characteristics at room temperature and ability to undergo a phase change to a semi-solid state with mucoadhesive behavior at physiological temperature has the potential to efficiently deliver therapeutics to brain. However, their application in nasal spray generation with favorable characteristics has not been investigated.

Methods: Thermosensitive chitosan (CS)-based formulations with different viscosities were prepared for intranasal delivery of ibuprofen using CS of various molecular weights. The formulation developed was optimized with regards to its physicochemical, rheological, biological properties and the generated aerosol characteristics.

Results: The formulations showed rapid gelation (4–7 min) at 30–35°C, which lies in the human nasal cavity temperature spectrum. The decrease in CS molecular weight to 110–150 kDa led to generation of optimum spray with lower Dv₅₀, wider spray area, and higher surface area coverage. This formulation also showed improved ibuprofen solubility that is approximately 100× higher than its intrinsic aqueous solubility, accelerated ibuprofen transport across human nasal epithelial cells and transient modulation of tight junctions.

Conclusions: A thermosensitive CS-based formulation has been successfully developed with suitable rheological properties, aerosol performance and biological properties that is beneficial for nose-to-brain drug delivery.     

pH敏感型原位凝胶的研究进展

pH敏感型原位凝胶随pH的变化而发生胶凝反应,缓慢持久地释放药物,可提高药物的生物利用度,是一种很有开发价值的新型药物传递系统。     

药物鼻黏膜递送的影响因素

鼻腔给药以其吸收快、使用方便、可避免药物胃肠道降解和肝脏首过效应、生物利用度高、实现脑靶向等特点，日益受到人们的重视，成为制剂学领域的研究热点之一。现综述影响药物在鼻腔内吸收的各种因素，包括生理因素、药物的理化性质、剂型和辅料的性质，以及给药装置的影响，为鼻腔给药系统的研究提供参考。     

Nanodiamonds as vehicles for systemic and localized drug delivery

Owing to their exceptional biocompatibility and unique surface properties, nanodiamonds (NDs) are shown to be a progressively promising nanomaterial for drug delivery. In this article, NDs as a platform for a host of biomedical applications are described, with an emphasis on cancer therapy, ranging from systemic modalities to primary constituents within polymer hybrid microfilms. Experimental results and theoretical explanations of ND–drug dynamics are compared. Water-dispersion of previously insoluble therapeutics when complexed with NDs demonstrates great promise in expanding current drug delivery options. Various forms of incorporating NDs within microfilms as a localized drug release coating and implant are also discussed.     

Prodrug strategies in nasal drug delivery

Nasal delivery offers a promising alternative to parenteral delivery. Prodrug strategies are usually aimed at modifying the parent drug such that favourable physicochemical and biological properties for absorption are obtained. Modulation of the drug hydrophilicity/lipophilicity or linkage of a moiety that will target membrane transporters or receptors may lead to enhanced drug absorption. A sizeable number of prodrug patents awarded in the past few years signal a high commercial potential for this approach. Novel developments include prodrug synthesis for drug delivery to the CNS via the nasal route. Prodrug modification also holds promise for intranasal delivery of anticancer drugs.     

Block copolymeric biotransport carriers as versatile vehicles for drug delivery

This review describes block co-polymer-based systems that are used in drug delivery. The main focus is on amphiphilic block co-polymers, the application of which modifies the pharmacological performance of various classes of drugs and is attracting more and more attention. The two main reasons for this are the high tendency of block co-polymer-based drug formulations to self-assemble and the flexibility of block co-polymer chemistry, which allows precise tailoring of the carrier to virtually any chemical entity. The combination of these and some other features makes it possible to adjust block co-polymer-based drug formulations to achieve the most beneficial balance in their biological interactions (biotransport), with systems that control drug removal from the body and those that are responsible for drug therapeutic activity. The following major aspects are considered:     

辛芷离子敏感型鼻用原位凝胶的研制及体外释药评价

目的:开发一种新型的中药鼻腔给药系统剂型—原位凝胶。方法:采用去乙酰结冷胶为材料制备辛芷离子敏感型鼻用原位凝胶。研究不同浓度去酰基结冷胶原位凝胶的黏度特性,采用扩散池法考察其体外释药规律,并用无膜溶出法研究其释药机制。结果:辛芷离子敏感型鼻用原位凝胶的黏度随去酰基结冷胶的浓度增加而增大,其释药量随结冷胶的浓度增加而减少,其释药符合一级释药模型,其溶蚀度较小且与释放率无明显相关性(r=0.986)。结论:应用去酰基结冷胶可成功制备离子敏感型中药鼻用原位凝胶,为中药鼻腔给药提供了一种新剂型。     

吗氯贝胺离子敏感型鼻用原位凝胶的制备及其体外释放度考察

目的:制备吗氯贝胺离子敏感型鼻用原位凝胶,并考察其体外释药行为。方法:以去乙酰结冷胶为凝胶基质,丙二醇、聚乙二醇-400及聚山梨酯-80为主要辅料,单因素试验法优选处方,并采用数学模型拟合体外释放曲线。结果:确定0.1%的结冷胶作为吗氯贝胺离子敏感型鼻用原位凝胶的基质,而体外释药行为符合Higuchi方程,该混合凝胶剂具有良好的体外缓释特征。结论:该处方设计合理,可作为经鼻给药的缓释载体。     

Fluorocarbon nanoparticles as multifunctional drug delivery vehicles

The history and current status of fluorocarbon nanoparticles in biomedicine is briefly reviewed. The deficiencies of current fluorocarbon nanoparticle formulations are highlighted. Strategies to remedy such deficiencies and to functionalize fluorocarbon nanoparticles are presented. Potential applications of fluorocarbon nanoparticles as multifunctional drug delivery vehicles are discussed. The strength of fluorocarbon nanoparticles as drug delivery vehicles is that they integrate drug delivery with non-invasive MR imaging so that the biodistribution of the pharmaceutical entity (drug+delivery vehicle) can be monitored in real time. This, in turn, permits the physician to adjust treatment plan for each patient based on his/her actual response to the ongoing treatment.     

眼用药物制剂研究进展

眼用给药系统在药学领域中有广阔的发展前景,是目前欧洲、日本、美国一些国家的研究热点之一.本文介绍了近几年来国内外眼用药物新剂型、新制剂的发展新动向、研究进展及趋势情况.     

Chitosan-based hydrogels for nasal drug delivery: from inserts to nanoparticles

Importance of the field: Chitosan represents a multifunctional polymer, featuring both mucoadhesive and permeation-enhancing properties and therefore is a widely studied excipient for mucosal drug delivery. As regards nasal administration, chitosans have been used for the preparation of gels, solid inserts, powders and nanoparticles in which a three-dimensional network can be recognized.

Areas covered in this review: This review provides a discussion of the different nasal dosage forms based on chitosan hydrogels. In the first section intranasal delivery is discuss as a useful tool for non-invasive administration of drugs intended for local or systemic treatments. Then chitosan-based hydrogels are described with a focus on their mucoadhesive and permeation-enhancing ability as well as their capacity of controlled drug release. Finally, a detailed discussion regarding several examples of the different nasal dosage forms is reported, including considerations on in vitro, ex vivo and in vivo studies.

What the reader will gain: Summary and discussion of recent data on the different pharmaceutical forms based on chitosan hydrogels could be of interest to researchers dealing with nasal drug delivery.

Take home message: The aim of this review is to stimulate further investigations in order to achieve the collection of harmonized data and concrete clinical perspectives.     

Formulation and evaluation of in situ gelling system of dimenhydrinate for nasal administration

Nasal drug delivery has a variety of advantages. Drugs can be rapidly absorbed through the nasal mucosa, giving rapid onset of action, and avoiding presystemic metabolism. In present study; the nasal mucoadhesive in situ gels of anti-emetic drug Dimenhydrinate were formulated using Gellan gum and Carbopol 934P. The in situ gels so prepared were characterized for gelation, viscosity, gel strength, mucoadhesion, drug content, drug diffusion, ex vivo permeation and histopathological studies. The optimized formulation passing from above tests was further subjected to accelerated stability study. It retained the good stability over the period of 90 days. From the overall performance this in situ gel seems to be an effective delivery system for the nasal route.     

Chitosan and its derivatives as vehicles for drug delivery

Abstract

Chitosan and its derivatives as vehicles for drug delivery can achieve the purpose of sustained release and controlled release for drugs, improve the stability of drugs, and reduce adverse drug reactions. So, the bioavailability of drugs can be enhanced. Therefore, chitosan and its derivatives have become a hotspot in the field of drug delivery. Their characteristics as drug delivery vectors were introduced, the types and applications were summarized. The development direction of chitosan and its derivatives in this field was also forecasted.     

聚合物在温度敏感型原位凝胶中的应用

多种聚合物可用于原位凝胶系统,使其随温度的变化而胶凝,缓慢持久地释放药物,在临床上有着广阔的应用前景。聚合物的开发应用必将不断地促进温度敏感型原位凝胶的快速发展。     

Polymeric micelles as nanocarriers for drug delivery

Polymeric micelles are built from amphiphilic polymers through self-assembly effects. Due to their unique core shell structure, small size and modifiable surface, polymeric micelles have been widely investigated as nanoscale drug delivery carriers. Such systems may increase drug solubility and have possible applications in tumour targeting and gene therapy. These biomedical applications require that polymeric micelles are biocompatible, have prolonged blood circulation and possess high drug-loading efficiency. In addition, tumour targeting and smart drug release behaviour need special modification towards micelles with multiplicate functional substances. This review focuses on the present progress of polymeric micelles and highlights some critical issues for their application in drug delivery systems. Composition and micellisation procedures are also briefly discussed.