壳聚糖及其衍生物作为药物载体研究进展

壳聚糖是甲壳素脱乙酰化的衍生物,是自然界中唯一的碱性多糖.壳聚糖及其衍生物是一类资源丰富、可生物降解的天然聚合物,具有生物相容性、高电荷密度、无毒性和粘膜粘附性,广泛应用于生物医学和药物制剂领域.壳聚糖作为药物载体可以控制药物释放、提高药物疗效、降低药物毒副作用,可以提高疏水性药物对细胞膜的通透性和药物稳定性及改变给药途径,还可以加强制刑的靶向给药能力.本文分别从壳聚糖及其衍生物在大分子药物载体、缓控释系统及不同部位给药系统中的应用进行了综述,以说明壳聚糖及其衍生物是一种优良的药物传递载体和新型药用辅料.     

海藻酸钠壳聚糖微球作为药物载体的研究进展

海藻酸钠壳聚糖微球是具有生物粘附性且能结合和传递大分子药物的天然高分子材料,且在生物医学领域具有广阔应用前景的药物载体。它具有生物黏附性、生物相容性、生物可降解性、对人体无毒性且能够结合和传递大分子药物的天然高分子材料。海藻酸钠壳聚糖微球作为载药微球具有提高药物的生物利用度、延长药物的作用时间等优点。国内外近些年已将其应用于药剂学领域,以及将其作为药物载体经微球化与药物结合形成给药系统的研究也在逐步开展并取得了较多成果。本文主要阐述海藻酸钠壳聚糖微球的主要生物特性、作用特点及其在医学领域中应用的研究进展,并对其应用前景进行探讨。     

抗肿瘤药物壳聚糖载体的研究进展

壳聚糖载抗肿瘤药物在各类具体药物中的应用取得了很大进展.用壳聚糖载抗肿瘤药物制成不同的剂型,可以有效解决抗癌药所具的低效、高毒、无选择性等问题,具有很大的研究开发潜力和良好的应用前景.本文就壳聚糖作为药物载体在杭肿瘤领城应用概况进行综述.     

壳聚糖作为基因药物载体的研究进展

以壳聚糖及其衍生物作为基因的载体的转染效率受到许多因素的影响, 如复合物粒子大小、壳聚糖/DNA的比值、壳聚糖的分子量、脱乙酰度、转染过程中血清的浓度、介质的pH值等。对壳聚糖进行一定程度的修饰, 可以改变壳聚糖的转染效率。介绍了壳聚糖作为基因转移载体的转染条件, 转染效率和转染机制的研究情况及研究进展。     

几丁质及其衍生物作为药物载体的应用

本文介绍了几丁质及其衍生物作为药物载体,制备各种剂型的缓释制剂方法和应用。     

壳聚糖作为基因治疗载体的研究

本文从壳聚糖－DNA复合物／微球的形成方法和机理,稳定性,转染细胞效率等方面综述了壳聚糖在基因治疗领域目前的研究现状。     

高分子药物缓释用壳聚糖微球的制备

本文采用了先交联制备可溶胀的壳聚糖载体微球,后将模型高分子药物以被动吸咐方式担载在溶胀的微球内的两步法,制备缓释高分子药物微球,避免了高分子药物接触有机试剂引起的活性损失。     

纳米微球药物缓释技术

纳米微球作为药物载体被越来越多地应用于医药领域,这一技术得到研究者的广泛重视。目前已有多种纳米微球制剂投入临床使用。纳米微球的深入研究具有重要的意义。我们概述了近年来纳米微球的研究及应用情况,展望了纳米微球药物载体缓释技术的应用前景及需要解决的问题。     

控释药物

在迅速发展的药剂学中,控释药物（ＣＲＤＤＳ）是控制释放给药系统（Ｃｏｎｔｏｒｌｅｄｒｅ－ｌｅａｓｅｄｒｕｇｄｅｌｉｖｅｒｙｓｙｓｔｅｍ）的简称。它是由美国人鲁滨逊（Ｒｏｂｉｎｓｏｎ）在１９７８年首先提出的。ＣＲＤＤＳ是通过物理、化学等方法改变制剂结构...     

纤维蛋白胶一药物缓释系统的研究进展

纤维蛋白胶作为一种生物蛋白制剂,除了应用于伤口止血、封闭组织缺损、防止组织粘连之外,也可以作为药物缓释载体。本文就纤维蛋白胶-药物缓释系统的研究及临床应用作以综述。     

载药脂质体的研究与应用进展

载药脂质体给药系统已成为国内外的研究热点。传统脂质体经修饰和改良后表现出良好的生物相容性,缓释性和靶向性。新型脂质体在经皮给药,肺部给药,脑部靶向治疗,基因治疗等方面的应用研究结果显示,集药物缓释、靶向于一体的具有良好生物安全性的脂质体给药系统具有很大发展潜力。本文综述了该领域中的最新研究进展。     

Evaluation of amylose used as a drug delivery carrier

The enzyme-dependent conjugates of indomethacin and amylose (Am-IND) were synthesized at room temperature using N,N′-dicyclohexylcarbodiimide (DCC) as a coupling agent and 4-(N,N′-dimethylamino) pyridine (DMAP) as a catalyst. Their structures were characterized by FTIR and ¹H NMR analyses, and the results indicated that the IND residues were conjugated with amylose backbones through ester bonds. For the conjugate with a lower IND content, the better water absorption property was advantageous for enzymes diffusing into the swollen conjugate, resulting in biodegradation of the conjugates and release of IND. In vitro biodegradation evaluation indicated that the Am-IND conjugates were biodegraded in the simulated media of the intestines. In vitro drug release experiments showed that the Am-IND conjugates exhibited a sustained release behavior in the simulated media of the intestines, while IND was hardly released in the simulated gastric fluid. These features provide a great opportunity to use the conjugates as a prodrug for intestinally targeted and controlled release of IND through oral administration. This study may lead to the development of effective methods for utilizing amylose as a new drug delivery carrier.     

Chitosan and lactic acid-grafted chitosan nanoparticles as carriers for prolonged drug delivery

Nanoparticles of approximately 10nm in diameter made with chitosan or lactic acid-grafted chitosan were developed for high drug loading and prolonged drug release. A drug encapsulation efficiency of 92% and a release rate of 28% from chitosan nanoparticles over a 4-week period were demonstrated with bovine serum protein. To further increase drug encapsulation, prolong drug release, and increase chitosan solubility in solution of neutral pH, chitosan was modified with lactic acid by grafting D,L-lactic acid onto amino groups in chitosan without using a catalyst. The lactic acid-grafted chitosan nanoparticles demonstrated a drug encapsulation efficiency of 96% and a protein release rate of 15% over 4 weeks. With increased protein concentration, the drug encapsulation efficiency decreased and drug release rate increased. Unlike chitosan, which is generally soluble only in acid solution, the chitosan modified with lactic acid can be prepared from solutions of neutral pH, offering an additional advantage of allowing proteins or drugs to be uniformly incorporated in the matrix structure with minimal or no denaturization.     

Preparation and characterization of sodium hexameta phosphate cross-linked chitosan microspheres for controlled and sustained delivery of centchroman

The cross-linked microspheres using chitosan with different molecular weights and degree of deacetylation have been prepared in presence of sodium hexameta polyphosphate (SHMP) as physical cross-linker. The degree of cross-linking through electrostatic interactions in chitosan microspheres has been evaluated by varying the charge density on chitosan and varying degree of dissociation of sodium hexameta polyphosphate by solution pH. The degree of deacetylation and molecular weight of chitosan has controlled electrostatic interactions between hexameta polyphosphate anions and chitosan, which played significant role in swelling, loading and release characteristics of chitosan microspheres for centchroman. The microspheres prepared by hexameta polyphosphate anions cross-linker were compact and more hydrophobic than covalently cross-linked microspheres, which has been attributed to the participation of all amino groups of chitosan in physical cross-linking with added hexameta polyphosphate anions. The microspheres prepared under different experimental conditions have shown an initial step of burst release, which was followed by a step of controlled release for centchroman. The extent of drug release in these steps has shown dependence on properties of chitosan and degree of cross-linking between chitosan and added polyanions. The degree of swelling and release characteristics of microspheres was also studied in presence of organic and inorganic salts, which shown significant effect on controlled characteristics of microspheres due to variations in ionic strength of the medium. The initial step of drug release has followed first order kinetics and become zero order after attaining an equilibrium degree of swelling in these microspheres. The microspheres prepared using chitosan with 62% (w/w) degree of deacetylation and molecular weight of 1134 kg mol⁻¹ have shown a sustained release for centchroman for 50 h at 4% (w/w) degree of cross-linking with SHMP.     

Miscibility study of chitosan/2-hydroxyethyl starch blends and evaluation of their effectiveness as drug sustained release hydrogels

Polymeric matrices of chitosan (CS), 2-hydroxyethyl starch (HES) and their blends prepared by solvent evaporation technique, have been tested as sustained release hydrogels of ropinirole drug. X-Ray diffraction (XRD), infrared spectroscopy (FT-IR) and viscometry measurements showed that the two polymers can form miscible blends. This miscibility is owed to formed hydrogen bonds taking place between the reactive groups of CS and HES and one glass transition is recorded in all blends. Neat polymers were used to prepare solid dispersion formulations with ropinirole drug. It was found that drug was released immediately within 15-30 min from HES while the release was slower from CS matrix. Completely different were the release rates from ropinirole with physical mixtures using neat polymers and their blends. Due to the different solubility and swelling behaviour of CS and HES the release rates showed a sustained profile from the blends containing high amounts of CS.     

Collagen peptide modified carboxymethyl cellulose as both antioxidant drug and carrier for drug delivery against retinal ischaemia/reperfusion injury

Oxidative stress can cause injury in retinal endothelial cells. Carboxymethyl cellulose modified with collagen peptide (CMCC) is of a distinct antioxidant capacity and potentially a good drug carrier. In this study, the protective effects of CMCC against H₂O₂‐induced injury of primary retinal endothelial cells were investigated. In vitro, we demonstrated that CMCC significantly promoted viability of H₂O₂‐treated cells, efficiently restrained cellular reactive oxygen species (ROS) production and cell apoptosis. Then, the CMCC was employed as both drug and anti‐inflammatory drug carrier for treatment of retinal ischaemia/reperfusion (I/R) in rats. Animals were treated with CMCC or interleukin‐10‐loaded CMCC (IL‐10@CMCC), respectively. In comparisons, the IL‐10@CMCC treatment exhibited superior therapeutic effects, including better restoration of retinal structural thickness and less retinal apoptosis. Also, chemiluminescence demonstrated that transplantation of IL‐10@CMCC markedly reduced the retinal oxidative stress level compared with CMCC alone and potently recovered the activities of typical antioxidant enzymes, SOD and CAT. Therefore, it could be concluded that CMCC provides a promising platform to enhance the drug‐based therapy for I/R‐related retinal injury.     

Gastroretentive drug delivery system of ranitidine hydrochloride: Formulation and in vitro evaluation

The purpose of this research was to prepare a gastroretentive drug delivery system of ranitidine hydrochloride. Guar gum, xanthan gum, and hydroxypropyl methylcellulose were evaluated for gel-forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of citric acid and stearic acid on drug release profile and floating properties were investigated. The addition of stearic acid reduces the drug dissolution due to its hydrophobic nature. A 3² full factorial design was applied to systemically optimize the drug release profile. The amounts of citric acid anhydrous (X₁) and stearic acid (X₂) were selected as independent variables. The times required for 50% (t₅₀) and 80% drug dissolution (t₈₀), and the similarity factor f₂ were selected as dependent variables. The results of the full factorial design indicated that a low amount of citric acid and a high amount of stearic acid favors sustained release of ranitidine hydrochloride from a gastroretentive formulation. A theoretical dissolution profile was generated using pharmacokinetic parameters of ranitidine hydrochloride. The similarity factor f₂ was applied between the factorial design batches and the theoretical dissolution profile. No significant difference was observed between the desired release profile and batches F2, F3, F6, and F9. Batch F9 showed the highest f2 (f2=75) among all the batches, and this similarity is also reflected in t₅₀ (∼214 minutes) and t₈₀ (∼537 minutes) values. These studies indicate that the proper balance between a release rate enhancer and a release rate retardant can produce a drug dissolution profile similar to a theoretical dissolution profile.     

Time-of-day variation in sustained attentional control

Sustained attention is a fundamental cognitive function underlying many activities in daily life including workplace safety, but its natural variation throughout the day is incompletely characterized. To examine time-of-day variation, we collected a large online data set (N = 6,363) with participation throughout the day and around the world on the gradual-onset continuous performance task, a sensitive measure of sustained attention. This allowed us to examine accuracy, attentional stability, and strategy. Results show that both accuracy and attentional stability peak between 9:00 and 11:00 a.m. and progressively decline throughout the day, whereas strategy is more stable.