药物控制释放用天然多糖载体的制备技术研究进展

药物的控制释放体系是生物医用材料研究领域的重要课题,其支撑点是要有性能良好的高分子药物载体。由于天然多糖作为药物控制释放材料具有比合成聚合物更多的优势,因而一直是国内外学者研究的重点。文章从微球与胶囊、水凝胶、压缩膜三方面分别对天然多糖药物载体的制备技术进行了简述,并提出了多糖研究中存在的主要问题和今后的研究重点。     

天然多糖类纳米凝胶药物载体的研究进展

天然多糖具有来源广泛、价格低廉、良好的生物相容性和生物可降解性等特点,被广泛应用于药物载体研究。天然多糖纳米凝胶内部交联网络结构能有效提高药物的稳定性,且自身带有大量的活性官能团,可以被修饰上靶向配体或者对病灶环境敏感的基团,使药物顺利到达靶向细胞,从而实现药物的可控释放,在提高药效的同时降低药物的毒副作用。该综述介绍了天然多糖类纳米凝胶作为药物载体的研究进展,包括壳聚糖、右旋糖酐、普鲁兰多糖、海藻酸盐、透明质酸以及肝素等天然多糖纳米凝胶用于环境响应药物可控释放和靶向药物治疗的研究状况,并对其未来发展方向进行了展望。     

药物微胶囊壁材研究进展

药物微胶囊在药物的缓控释放等方面有着广阔的应用前景,因而近年来正成为农药、医药新剂型领域研究的热点之一。开发有竞争力的微胶囊壁材是当前药物微胶囊研究领域的一个重要课题。本文从天然高分子材料、全合成高分子材料、半合成高分子材料及无机材料4个方面综述了药物微胶囊壁材研究与应用的最新进展,着重阐述了明胶-阿拉伯胶、壳聚糖-海藻酸钠、环糊精及其衍生物、聚乳酸及其共聚物、脂肪族聚碳酸酯等生物可降解高分子材料作为药物微胶囊壁材的研究进展。     

基于生物大分子的纳米药物载体

生物大分子材料由于其可再生性、无毒性以及良好的生物相容性、生物可降解性和黏膜粘附性等特点成为药物载体研究的热点,尤其是将其作为纳米药物载体材料更加受人关注。本文首先对生物大分子纳米颗粒常用的制备方法--乳化法、自组装法和离子凝聚法进行了详细的介绍。由于乳化法在一定程度上破坏了生物大分子的生物相容性,因此自组装法和离子凝聚法是比较理想的制备方法。其中自组装法是利用两亲性的生物大分子,如蛋白质、多糖衍生物等在静电作用、疏水作用、范德华力等非键合作用力下组装成纳米结构;而离子凝聚法则是利用聚电解质与带相反电荷物质之间的静电作用形成纳米结构。接着本文对通过这些方法获得的生物大分子纳米颗粒作为蛋白类药物、抗癌药物以及基因药物的载体在近年来的研究进展进行了归纳和总结,结果显示其在药物缓释体系中具有广阔的应用前景。     

壳聚糖及其衍生物基因载体的研究进展

壳聚糖是一种天然的生物可降解性,生物相容性好而且安全无毒的多糖,因而它成为基因治疗载体研究的热点。本文就近年来壳聚糖及其衍生物作为基因载体转染的研究进展和现状作简要的综述,并对转染率的影响因素如壳聚糖的分子量、粒径、脱乙酰度等进行着重介绍。     

天然多糖作为核酸载体的研究

基因治疗这种堪称革命性的治疗方法,开拓了治疗癌症的新思路,其最关键性问题是实现核酸药物靶向肿瘤组织并精准治疗。核酸药物直接递送存在核酸酶降解代谢、细胞膜上的负电荷排斥现象以及稳定性差等问题,所以核酸药物需要载体协助,成功的载体递送除能使核酸药物在肿瘤区域大量富集外,还要起到药物控释作用,而天然多糖除无毒、生物相容度高、易修饰的特点外,它本身就具有免疫调节、抗肿瘤、抗炎等多种生物活性。本篇总结了最具代表性的五种多糖的结构特征及在核酸药物递送方面的应用,继而归纳了多糖的常用的纳米级载体形式,为构建天然多糖递送核酸的新型载体并将其应用到免疫抗肿瘤治疗研究中奠定基础。     

层层组装微胶囊的制备及其智能响应与物质包埋释放性能

在胶体微粒模板上进行聚合物间或聚合物和小分子间的交替层层(LBL)组装, 得到核壳微粒, 然后去除胶体微粒得到层层组装微胶囊. 综述了层层组装微胶囊在组装驱动力、智能响应性能和物质包埋与释放等方面的最新研究进展. 首先从组装驱动力和微胶囊结构调控出发, 简述了基于静电和氢键作用的LBL微胶囊的交联方法及交联所引起的微胶囊结构和性能的变化, 介绍了基于新驱动力如共价键作用、 碱基对作用和主客体作用制备LBL微胶囊的技术. 讨论了LBL微胶囊的智能响应性, 包括pH、 温度、 电荷、 光电磁和化学物质响应等. 详细介绍了LBL微胶囊包埋与释放功能物质尤其是药物、 蛋白和酶的方法及其特色, 包括LBL直接包埋与释放、 预吸附或共沉淀包埋与释放、 电荷选择性自沉积包埋与释放及爆释等. 最后, 着眼于微胶囊的靶向传递和功能器件, 介绍了采用静电作用和生物识别作用制备得到的微胶囊阵列.     

交联聚乳酸中空微球的制备与表征

由于聚乳酸具有良好生物相容性与降解性,故可用作控释给药系统的载体材料．有关聚乳酸及其共聚物微球药物载体、释放行为及微球表面引入基团使之功能化的方法研究已有报道．以其它生物大分子材料作为囊壁材料的缓释微胶囊也有报道,但以聚乳酸制备中空微囊型的药物释放载体却鲜有研究．通过控制分子量、微囊大小、囊壁厚度等参数,     

天然香料纳微胶囊中间体

作为一种中间体,天然香料纳微胶囊具有可控释放、保护活性成分的优势,已经被广泛应用于食品、日化和纺织等很多领域。然而,天然香料纳微胶囊的结构与性能的不可控限制了其在高技术领域的进一步应用。天然香料纳微胶囊属于结构化产品,性能不仅取决于比例和组成,微观与介观结构也起着重要的作用。本课题组在化学产品工程理念的指导下,以产品需求为导向,从分子水平研究芯材与壁材分子间的相互作用,建立天然香料纳微胶囊结构与性能的关系,通过多壁材复合技术、微流控技术与过程控制技术实现化学品的精确定制。本文综述了天然香料纳微胶囊在不同领域中的应用进展,重点探讨用化学产品工程理念来设计、制备天然香料纳微胶囊,并对该领域所面临的挑战和未来的研究方向进行了展望。     

PNIPA类纳米水凝胶在药物缓控释研究中的应用

简要介绍了聚N-异丙基丙烯酰胺(Poly N-isopropylacrylamide, PNIPA)类纳米水凝胶的性质及智能响应机理,并重点综述了近年来此类纳米水凝胶在药物缓控释研究中的应用:作为脂溶性小分子药物的载体,达到增溶及缓控释药物的效果,并增强药物的稳定性及生物活性;作为水溶性小分子药物的载体,达到缓释该类药物的效果;作为生物大分子药物(蛋白,多糖)的载体,克服直接用药时的弊端;此外,还可作为基因工程载体.     

Synthesis and functionalization of monodisperse poly(ethylene glycol) hydrogel microspheres within polyelectrolyte multilayer microcapsules

Polyelectrolyte multilayer microcapsules were used as templates to prepare monodisperse poly(ethylene glycol) (PEG) hydrogel microspheres, which can react with amine-bearing molecules.     

刺激响应型微胶囊的可控释放研究进展

刺激响应型微胶囊由于具有独有的高稳定性、多功能性、膜结构的可调性、以及对不同芯材的运送能力,在药物封装和释放、人造细胞、催化、化学传感器等领域具有广阔的应用前景.本文综述了近年来不同刺激响应型复合微胶囊的可控释放的研究进展,包括温敏型、pH响应型、磁响应型、生物响应型、电响应型,以及光响应型微胶囊,根据释放机理的不同着重对光响应型微胶囊的释放过程进行了总结,并对微胶囊可控释放在未来的发展趋势进行了展望.     

Cultivation of Encapsulated Primary Human B Lymphocytes: A First Step toward a Bioartificial Germinal Center

Polyelectrolyte microcapsules based on sodium cellulose sulfate (SCS) and poly-diallyl-dimethyl-ammonium chloride (PDADMAC) have previously been proposed as a suitable ex vivo microenvironment for the cultivation and differentiation of primary human T lymphocytes. Here, the same system is investigated for the cultivation of human primary B cells derived from adult tonsillar tissue. Proliferation and differentiation into subtypes are followed and compared to suspension cultures of B cells from the same pool performed in parallel. Total cell expansion is somewhat lower in the capsules than in the suspension cultures. More importantly, however, the differentiation of the initially mainly memory B cells into various subtypes, in particular into plasma cell (PC), shows significant differences. Clearly, the microenvironment provided by the microcapsules is beneficial for an accelerated induction of a germinal center-like B cell phenotype and afterward supports the long-term survival of the PC cells. Then, varying the encapsulation conditions (i.e., presence of human serum and dedicated cytokines in the capsule core) provides a tool for finetuning the B cell response. Hence, this methodology is suggested to pave the way toward ex vivo development of human immune organoids.     

Effect of Crosslinking Agent on Neem (Azadirachta Indica A. Juss.) Seed Oil (NSO) Encapsulated Microcapsules of κ -Carrageenan and Chitosan Polyelectrolyte Complex

Microencapsulation of neem (Azadirachta Indica A. Juss.) seed oil (NSO) was carried out by polyelectrolyte complexation of κ -carrageenan and chitosan. The microcapsules were crosslinked by using three different crosslinking agents - glutaraldehyde, genipin and tannic acid. The lowest and highest water uptake capacities were exhibited by glutaraldehyde and tannic acid crosslinked matrices, respectively. The release behavior of NSO from encapsulated crosslinked microcapsules followed the order: tannic acid > genipin > glutaraldehyde. Polyelectrolyte complex formation and its interaction with crosslinker was studied. Crosslinking improved thermal stability without affecting crystallinity. Roughness appeared on microcapsule's surface indicated interaction between microcapsules and crosslinker.     

Degradation of PEG and non-PEG alginate-chitosan microcapsules in different pH environments

Bioencapsulation allows the protection of biologically active substances or cells from the biological environment. As such, bioencapsulation is often used for the delivery of drugs, growth factors and therapeutically useful cells. Depending on the site of implantation, the biocapsules are subjected to different pH environments, which will affect the degradation properties, mechanical properties and swelling behaviour of the biocapsules. As such, the encapsulation material plays an important role in the long term stability and performance of the biocapsules in vivo. In this study, five types of encapsulation materials were investigated: (i) alginate (A), (ii) alginate-chitosan (AC), (iii) alginate-chitosan-alginate (ACA), (iv) alginate-chitosan-polyethylene glycol (PEG) (ACP) and (v) alginate-chitosan-polyethylene glycol (PEG)-alginate (ACPA). Degradation studies were carried out by immersing the microcapsules in solutions of different pH values to investigate the role of the material as well as the number of encapsulation layers in maintaining the stability of the microcapsules in the different pH environments. Compression testing indicated that even with the presence of PEG on the surface membrane, there was not much difference in mechanical strength between ACA and ACPA microcapsules. However, the use of PEG did affect the weight change of the ACPA microcapsules when immersed in water and three different pH solutions. For the swelling test, the ACPA microcapsules showed a lower water uptake than ACA microcapsules. For degradation, the presence of PEG led to a lower increase in weight change compared to non-PEG chitosan microcapsules. Hence, the study revealed that PEG influenced the integrity of the surface membrane and not the mechanical strength of the microcapsules. With the inclusion of PEG, the interpenetrating network on the surface membrane would be further reinforced. As such, the addition of PEG to the alginate-chitosan microcapsules led to protection against an acidic environment, whilst the number of coating layers only influences the swelling properties and not the degradation and Young’s modulus of the microcapsules.     

磁性微胶囊的制备及其药物缓控释性能

用乳液-凝胶法制备了磁性壳聚糖/海藻酸钠微胶囊. 在壳聚糖/海藻酸钠微胶囊中掺入Fe3O4磁性中空球, 使微胶囊具有磁靶向性能. 以头孢拉定作为模型药物研究了载药磁性微胶囊的载药量、包封率及药物缓控释性能等. 结果表明, 提高头孢拉定的初始浓度可以提高载药量, 却不利于提高药物的包封率. 所制备的微胶囊在各种缓冲溶液中长时间内具有显著的缓释效果, 并具有pH 刺激响应释放的性能, 即在模拟胃液中的药物释放率大大降低, 而在模拟体液和肠液中的释放时间大大延长, 可达50 h以上. 另外, 在外加磁场作用下, 微胶囊表现出良好的磁定向运动性能, 为磁靶向药物输送提供基础.     

Hollow microcapsules built by layer by layer assembly for the encapsulation and sustained release of curcumin

Hollow microcapsules fabricated by layer-by-layer assembly (LbL) using oppositely charged polyelectrolytes have figured in studies towards the design of novel drug delivery systems. The possibility of loading a fair amount of active component of poor aqueous solubility is one of the encouraging factors on the wide spread interest of this emerging technology. Curcumin has potent anti-cancer properties. Clinical application of this efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility and consequently minimal systemic bioavailability. LbL constructed polyelectrolyte microcapsules based drug delivery systems have the potential for dispersing hydrophobic agent like curcumin in aqueous media. Here we report the preparation of LbL assembled microcapsules composed of poly(sodium 4-styrene sulfonic acid) and poly(ethylene imine) one after another. The microcapsules were characterized using various analytical techniques. Curcumin was encapsulated in these microcapsules and the efficacy of the released curcumin was studied using L929 cells.     

Controlled release by polyelectrolyte microcapsule membranes

Polyelectrolyte submicron microcapsules were prepared by interfacial crosslinking of an aqueous salt solution of poly(ethyleneimine) and a toluene solution of brominated poly-(2,6-dimethylphenylene oxide). The two solutions were brought together and mixed by sonication. As a result, a stable emulsion was obtained, which was subsequently cast into a membrane in which the microcapsules were embedded. The salt solution contained in the microcapsules could be released under controlled conditions. The rates of release were measured. They could be controlled by applying osmotic pressures, by additional quaternization of the membrane, or by modification of the structure of the capsule wall by introduction of a surfactant.     

Avidin/PSS membrane microcapsules with biotin-binding activity

Polyelectrolyte microcapsules with avidin-poly(styrene sulfonate) (PSS) membrane were prepared by a layer-by-layer deposition technique. The uptake and release of biotin-labeled fluorescein (b-FITC) as well as immobilization of biotin-labeled glucose oxidase (b-GOx) to the microcapsule were studied. The polyelectrolyte microcapsules were prepared by coating the surface of calcium carbonate (CaCO(3)) microparticles with an avidin/PSS multilayer membrane, followed by dissolution of CaCO(3) core in an ethylenediaminetetraacetic acid solution. Inner and outer poly(allylamine)/PSS films were required to isolate the microcapsules, whereas microcapsules could not be formed without the support. The uptake of b-FITC into the microcapsule was highly enhanced through a strong binding of b-FITC to avidin as compared with the uptake of biotin-free FITC. Release of b-FITC from the microcapsule was accelerated upon addition of biotin due to a competitive binding of the added biotin to the binding site of avidin. Similarly, the surface of microcapsule was modified with b-GOx with retaining its catalytic activity.     

Performances of NaCS–WSC protein drug microcapsules with different degree of substitution of NaCS using sodium polyphosphate as cross-linking agent

Sodium cellulose sulfate–water soluble chitosan (NaCS–WSC) microcapsules loaded with lactoferrin were fabricated with special performances using different degree of substitution (DS) of NaCS and WSC as potential micro-drug-carriers for colon. Effect of using cross-linking agent (sodium polyphosphate) and DS of NaCS on the structures and performances of microcapsules was studied. The results of laser scanning confocal microscope showed that fluorescein isothiocyanate-labeled lactoferrin distributed evenly in the drug-loaded microcapsules with cross-linker. NaCSs (DS: 0.51 and DS: 0.66, respectively) were chosen to prepare lactoferrin loaded microcapsules with WSC and cross-linker for comparison studies. DS of NaCS had some effects on erosion properties in which the erosion ratios of microcapsules with DS of 0.51 were higher than that with DS of 0.66, but showed no effect on swelling behaviors. Drug loading and encapsulation efficiencies of microcapsules (DS: 0.66) were 51.05 ± 0.97 and 75.88 ± 1.44 %, respectively, which were higher than that of microcapsules with DS of 0.51. In vitro release studies showed that the percentage of drug release of microcapsules (DS: 0.51) were higher than that of microcapsules with DS of 0.66 in simulated colonic fluid (pH 6.4) under mechanism of Anomalous (non-Fickian) transport, indicating that they are promising candidates as sustained protein drug delivery carriers with special performances.