难溶性药物注射给药系统的研究进展

由于高通量筛选技术在药物开发上的广泛应用,涌现了越来越多水难溶性的新化合物.注射剂在临床治疗中发挥着重要的作用,但水溶性低却成了这些化合物开发成注射剂的一个主要难题.本文综述了微乳、亚微乳、前药、环糊精包合物、纳米混悬剂和聚合物胶束系统等在难溶性药物注射给药方面的应用,以期能通过比较各给药系统的优缺点,为产品的开发提供思路.     

抗肿瘤药物微乳给药系统研究进展

目的 介绍微乳给药系统在抗肿瘤药物中的研究进展,为深入研究提供参考.方法 根据国内、国外文献报道,对微乳给药系统的处方组成、成型工艺以及在抗肿瘤药物中的应用等方面进行综述.结果与结论 微乳给药系统能够提高水溶性差的抗肿瘤药物的生物利用度,提高疗效,适合口服给药,方便患者服用.     

静脉注射多西他赛亚微乳在大鼠的组织分布及排泄研究

目的研究比较多西他赛(docetaxel,DTX)亚微乳注射剂及普通注射剂在大鼠体内的组织分布及原型药物的排泄情况。方法以DTX注射剂(商品名:泰索帝)为参比,48只SD大鼠随机分成2组,分别经尾静脉注射DTX亚微乳注射剂(75 mg.m-2)和DTX注射剂(75 mg.m-2),在给药后5、30、60、300 min各处死6只大鼠,于相应部位取各组织适量。另取大鼠10只,随机分为2组,分别静脉注射亚微乳注射剂或普通注射剂(75 mg.m-2),收集给药前及给药后0~4、4~10、10~18、18~24、24~36 h的尿液、粪便。组织及排泄物中的DTX浓度以HPLC-UV法测定。结果 DTX亚微乳注射剂及普通注射剂在体内分布广泛而迅速。DTX亚微乳在心和肺中的浓度显著低于注射剂(P<0.05),但在脾脏中的浓度高于注射剂(P<0.05)。肾脏中的分布在早期较注射剂明显增加,后期较注射剂明显降低(P<0.05),其他组织器官的分布无显著性差异(P>0.05)。两者经粪便和尿液排泄的原型药物无显著性差异(P>0.05),36 h尿排累积百分率均<2%,粪排累积百分率均<6%。结论与普通注射剂相比,亚微乳不影响DTX在大鼠体内的原型药物排泄。在安全性及药效学评价中,应特别关注剂型改变后心、肺、肾及脾脏的毒性及药效变化。     

天然药物靶向给药系统的研究

采用新型药物载体使天然药物具有靶向作用是近年来药剂学的研究热点之一。综述脂质体、纳米粒、微球、微乳、药质体等新型载体在天然药物靶向给药系统研究中的应用,并介绍膜融合脂质体、纳米脂质载体、药脂结合物纳米粒以及分泌颗粒类似物等几种新型靶向给药系统的药物载体。     

微乳及自微乳给药系统的药学应用进展

目的介绍微乳及自微乳给药系统的最新进展及在药学研究方面的应用。方法查阅国内外文献资料进行整理和归纳。结果微乳及自微乳给药不仅能改善难溶于水、油溶性药物的溶解性,也可以保护不稳定的药物,控制药物的释放,它可以用于多种给药途径。结论此类给药系统是非常有前景的给药系统。     

去甲斑蝥素新型制剂研究进展

目的 综述去甲斑蝥素新型制剂研究进展.方法 通过查阅近年来有关去甲斑蝥素新型制剂的中外文献,对其研究进展进行归纳总结与分析.结果 经过对微球、纳米粒、脂质体和微乳等载药系统包载去甲斑蝥素的情况进行分析,结果表明去甲斑蝥素新型制剂是极具开发潜力的新型制剂.结论 去甲斑蝥素是一种优良的抗肿瘤药物,但传统的注射剂和片剂在临床...     

微乳给药系统研究进展

微乳是一种新型给药系统，能提高水难溶性药物的溶解度和生物利用度，延长水溶性药物的释放，并具有较好的靶向性。近年来研究表明，微乳有利于药物的吸收、分布，可改善药动学，在透皮与口服给药、新制剂研发中得到应用。     

制剂新技术和新型给药系统在蛋白多肽药物研究中的应用

蛋白多肽药物已经成为国内外药学研究和开发的热点,文中介绍几种新制剂技术和新型给药系统在多肽蛋白药物中的应用,分别阐述了聚乙二醇(PEG)修饰技术、聚乙烯吡咯烷酮(PVP)修饰技术、超临界流体技术和脂质体、微粒和纳米粒、脉冲给药系统、微组装给药系统、微乳、聚合物胶束等的应用和研究新成果.上述新技术和新给药系统研究在多肽蛋白药物制备中取得较大进展,明显改善了蛋白多肽的稳定性和体内药动学性质,在新蛋白多肽药物研究中有广阔的应用前景.     

蛋白质多肽长效微球注射剂的体内药动学及分析方法研究进展*

长效微球注射剂作为一类处于热点研究中的新型释药系统，在蛋白质、多肽的递送中受到了日益广泛的重视和应用。但是，微球的释药机制复杂，蛋白质、多肽的体内药物分析又存在着诸多困难，因而蛋白质、多肽长效微球注射剂的体内药物释放及评价是此类药物制剂研发的瓶颈之一。现介绍近年来蛋白质、多肽长效微球注射剂的体内释药机制及药动学研究进展，并着重对蛋白质、多肽长效微球注射剂的体内药物分析方法进行综述。     

自微乳释药系统研究进展

简要介绍了自微乳释药系统的组成、体外释药研究方法及自微乳新型制剂的研究进展.自微乳新型制剂主要包括固体自微乳、过饱和自微乳和正电荷自微乳,新型自微乳制剂可以弥补其不足,更好地发挥自微乳固有特点.     

Light-responsive in situ forming injectable implants for effective drug delivery to the posterior segment of the eye

ABSTRACT

Introduction: Frequent intravitreal injections are currently the preferred treatment method for diseases affecting the posterior segment of the eye. However, these repeated injections have been associated with pain, risk of infection, hemorrhages, retinal detachment and high treatment costs. To overcome these limitations, light-responsive in situ forming injectable implants (ISFIs) may emerge as novel systems providing site-specific controlled drug delivery to the retinal tissues with great accuracy, safety, minimal invasiveness and high cost efficiency.

Area covered: Complex ocular barriers, routes for drug delivery, types of injectable implants, ocular application of light and benefits of light-responsive systems are discussed with regards to challenges and strategies employed for effective drug delivery to the posterior segment of the eye. In particular, we have highlighted photoresponsive moieties, photopolymerization mechanisms and different development strategies with their limitations as well as recent advancements in the field.

Expert opinion: Biodegradable light-responsive ISFIs are promising drug delivery systems that have shown a high degree of biocompatibility with sustained drug release in a number of applications. However, their use in intravitreal drug delivery is still in the very early stages. Issues related to the biocompatibility of the photoinitiator and the elimination of photo-degraded by-products from the ocular tissues need careful consideration, not only from a chemistry standpoint, but also from a biological perspective to improve the suitability of these systems for clinical applications.     

Modified release intra-articular drug delivery systems

Beside the many advantages of intraarticular formulations (e.g., the systemic side effects are kept away), there is a big drawback. During the injections, there is the risk for infection therefore the number of injections in a year should be reduced. Also a long-term drug exposure should be achieved with an injection, and if it is possible, a combination of active ingredients should be used. At present there are only formulations with hyaluronic acid or glucocorticoid on the market. One of these formulations, a liposomal preparation, is of sustained drug release. Many different active ingredients could have a long-term drug exposure with carrier systems like micro- and nanoparticles, liposomes, hydrogels and physically activated delivery systems (thermoresponsive or magnetically modulated). The present paper gives an overview about these carrier systems, the novel scientific results and the aim of the future researches, as well.     

Parenteral drug delivery: a review

The parenteral route of administration is the most effective route for the delivery of the active pharmaceutical substances with narrow therapeutic index, poor bioavailability especially for those drugs, prescribed to unconscious patients. To maintain a therapeutic effective concentration of the drug, it requires frequent injections which ultimately lead to patient discomfort. In parenteral drug delivery, major progress has been done in the field of formulation technologies so as to provide a targeted and sustained release of drug in predictable manner. The present article reviews recent patents and major advancements in parenteral drug delivery systems along with general introduction. This article also deals with importance of novel systems in drug delivery to overcome the problems associated with conventional parenteral drug delivery systems.     

Drug delivery strategies for the treatment of malignant gliomas

As primary brain tumors, malignant gliomas are known to be one of the most insidious types of brain cancer afflicting the humans. The current standard strategy for the treatment of malignant gliomas includes the surgical resection of the tumor when possible, followed by a combination of radiotherapy and/or a certain chemotherapeutic protocol. However, due to the short mean survival, frequent recurrences, and poor prognosis associated with the tumors, new therapeutic strategies are investigated consecutively. These novel drug delivery approaches can be subdivided as systemic and local drug administration. This review focuses on localized drug delivery strategies for the treatment of malignant gliomas, including the injections, infusions, trans-nasal delivery systems, convection enhanced delivery (CED) systems, and various types of polymeric implants. Furthermore, systemic strategies to increase the drug penetration into the brain, such as temporary disruption of the blood brain barrier (BBB), chemical modification of the available therapeutic substances, and utilization of endogenous transport systems will be briefly discussed.     

Biodegradable Implants for Sustained Drug Release in the Eye

The safety and effectiveness of systemic and topical medical therapies for ocular disorders are limited due to poor ocular drug uptake, nonspecificity to target tissues, systemic side effects, and poor adherence to therapy. Intravitreal injections can enhance ocular drug delivery, but the need for frequent retreatment and potential injection-related side effects limit the utility of this technique. Sustained-release drug delivery systems have been developed to overcome these limitations; such systems can achieve prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure and side effects and improving patient adherence to therapy. A critical factor in the development of safe and effective drug delivery systems has been the development of biocompatible polymers, which offer the versatility to tailor drug release kinetics for specific drugs and ocular diseases. Ocular implants include nonbiodegradable and biodegradable designs, with the latter offering several advantages. The polymers most commonly used in biodegradable delivery systems are synthetic aliphatic polyesters of the poly-α-hydroxy acid family including polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid. The characteristics of these polymers for medical applications as well as the pharmacological properties, safety, and clinical effectiveness of biodegradable drug implants for the treatment of ocular diseases are reviewed herein.     

Biodegradable microspheres for vitreoretinal drug delivery.

Vitreoretinal disorders are one of the major causes of blindness in the developed world. Treatments of these pathologies often include repeated intravitreous injections to achieve intraocular drug levels within the therapeutical range. However, the risks of complications increase with the frequency of intravitreous injections. Controlled drug delivery formulations, offer an excellent alternative to multiple administrations. These systems are capable of delivering drugs over longer time periods than conventional formulations. Currently, several kinds of polymer devices for drug delivery to the posterior segment of the eye are under clinical use, or under investigation. Among these devices, microparticulates, such as microspheres, provide an alternative to multiple injections to obtain sustained release of the drug with a single administration. Among the polymers used to make the injectable microparticles, the most commonly used are poly(lactic acid), poly(glycolic acid) and copolymers of lactic and glycolic acids because they are biocompatible and degrade to metabolic products that are easily eliminated from the body. This article reviews the literature of biodegradable polymeric microspheres loaded with drugs, that have been investigated for delivery by intravitreous injection to treat diverse vitreoretinal diseases.     

Multiphase flow microfluidics for the production of single or multiple emulsions for drug delivery

Considerable effort has been directed towards developing novel drug delivery systems. Microfluidics, capable of generating monodisperse single and multiple emulsion droplets, executing precise control and operations on these droplets, is a powerful tool for fabricating complex systems (microparticles, microcapsules, microgels) with uniform size, narrow size distribution and desired properties, which have great potential in drug delivery applications. This review presents an overview of the state-of-the-art multiphase flow microfluidics for the production of single emulsions or multiple emulsions for drug delivery. The review starts with a brief introduction of the approaches for making single and multiple emulsions, followed by presentation of some potential drug delivery systems (microparticles, microcapsules and microgels) fabricated in microfluidic devices using single or multiple emulsions as templates. The design principles, manufacturing processes and properties of these drug delivery systems are also discussed and compared. Furthermore, drug encapsulation and drug release (including passive and active controlled release) are provided and compared highlighting some key findings and insights. Finally, site-targeting delivery using multiphase flow microfluidics is also briefly introduced.     

Intraoral drug delivery

The oral availability of many drugs is poor because of the pH of the stomach, the presence of enzymes, and extensive first-pass metabolism. Traditionally, these drugs have been administered as parenteral drug delivery systems, which invariably leads to poor patient compliance. This has made the pharmaceutical industry look for alternative routes of drug delivery. One possible route is via the oral cavity. This review compares the many different and novel drug delivery systems that have been developed for absorption through the oral cavity as well as those that undergo quick disintegration or dissolution in the oral cavity. Systems for oral delivery include mucoadhesive patches, films and tablets, as well as quick-disintegrating wafers, tablets and films. There are many examples of drugs that have been formulated into intraoral absorptive drug delivery systems as well as quick-disintegrating drug delivery systems. The fact that most of the research being conducted on intraoral drug delivery systems is driven by pharmaceutical manufacturers demonstrates the need for such drug delivery systems. As we begin to discover more about oral mucosal drug delivery, and develop much more sophisticated drug delivery systems, many more drugs will be formulated as intraoral systems. There is no doubt that the need for these systems is real, and many classes of drugs could benefit from this noninvasive type of drug delivery. The challenge now is to synthesize drug moieties that exhibit increased absorption across the oral mucosa and are more potent in their action. Intraoral drug delivery systems are possibly one of the very few drug delivery systems that seem to be ahead of the development of new drug compounds that are effectively absorbed across tissue membranes.     

Periocular routes for retinal drug delivery

Despite numerous scientific efforts, delivery of therapeutic amounts of a drug to the retina remains a challenge. This challenge is compounded if chronic therapy is desired. The inability or inefficiency of topical and systemic routes for retinal delivery of existing drugs is now widely accepted. Although the intravitreal route offers high local concentrations in the vitreous and, hence, retina, these advantages are offset by side effects, such as cataracts, endophthalmitis and retinal detachment, following repeated intravitreal injections, or intravitreal placement of sustained-release implants. As discussed in this review, periocular routes, including subconjunctival, sub-tenon, retrobulbar, peribulbar and posterior juxtascleral routes, potentially offer a more promising alternative for enhanced drug delivery to the retina compared with topical and systemic routes. Periocular routes exploit the permeability of sclera for retinal drug delivery, and they are particularly useful for administering sustained-release systems of potent drugs. This review discusses the various periocular routes with respect to their anatomical location, pharmacokinetics, safety and mechanisms of drug delivery. In the coming years, several innovations in absorption enhancement, drug delivery systems and drug administration devices are anticipated for improving retinal drug delivery via periocular routes.     

新型胃滞留给药系统的研究进展

目的介绍新型胃滞留给药系统近年来的研究进展,为研究开发胃滞留制剂提供参考。方法通过查阅近年国内外相关文献,进行分析、整理和归纳。结果胃滞留给药系统能改善药物吸收,有效提高生物利用度,其中,以漂浮型、生物黏附型、膨胀型等三类胃滞留给药系统的研究较多。结论随着对胃滞留给药系统的深入研究,以及新型药用高分子材料的开发和制剂新技术的发展,胃滞留制剂具有广阔的应用前景。