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,     

不同溶剂制备的聚乳酸多孔微球的形成机理

利用改进的双乳液溶剂挥发法制备了多孔聚乳酸( PLA)微球.通过采用具有不同沸点和水溶性的有机溶剂制备得到不同多孔结构的PLA微球.结果发现以二氯甲烷、氯仿和甲苯为溶剂制备的微球具有相似的均匀多孔结构,而以乙酸乙酯制备的微球却具有中空结构和多孔的壳层.通过进一步的实验研究了溶剂种类对于微球多孔结构的影响.结果表明溶剂的...     

聚乳酸载药微球制备及释药性能研究最新进展

对可生物降解材料聚乳酸作为药物载体制备微球制剂的研究状况进行了综述。针对目前限制聚乳酸微球制剂临床应用存在的问题,重点介绍了降低药物突释,提高药物包封率,改善多肽和蛋白药物微球释药性能等方面研究的最新进展。聚乳酸载药微球在药物传输中有着广阔的研究和应用前景。     

单糖类化合物改性聚乳酸的研究进展

聚乳酸（PLA）作为一种性能良好的生物可降解材料,在生物医用高分子等方面有着广泛的应用。单糖类小分子对多肽、蛋白质等具有较好的亲和性,对组织细胞也有较好的相容性。为了改善PLA的亲水性、细胞相容性等性能,利用单糖类化合物改性聚乳酸日益受到关注。按照单糖种类的不同,本文综述了近年来各类单糖及其衍生物等改性聚乳酸的研究进展...     

改性羟基磷灰石/聚乳酸纳米复合材料的结晶行为

利用溶剂复合的方法制备了具有良好生物相容性的表面接枝聚(γ-苄基-L-谷氨酸)的改性羟基磷灰石/聚乳酸纳米复合材料, 并研究了其熔融与结晶行为. 结果表明, 聚乳酸的玻璃化转变温度为60.3 ℃, 而复合材料的玻璃化转变温度达到65.8 ℃, 不同样品在140 ℃等温结晶后, 改性羟基磷灰石/聚乳酸复合材料的球晶直径仅为聚乳酸(PLLA)球晶直径的16.7%~66.7%. 复合材料的熔点提高到184.4 ℃.     

羧甲基香菇多糖表面修饰的聚乳酸材料的表面性能研究

制备了香菇多糖羧甲基衍生物,再通过化学接枝方法利用共价键将羧甲基香菇多糖固定在氨基化聚乳酸基材表面,得到羧甲基香菇多糖化学接枝修饰的聚乳酸材料.此外,通过在氨基化聚乳酸基材表面进行羧甲基香菇多糖与壳聚糖的层层自组装,得到生物多糖层层自组装修饰的聚乳酸材料.采用扫描电子显微镜、水接触角测量仪、抗菌活性测试、溶血试验和血栓试验等方法对被修饰聚乳酸材料的表面性能和生物性能进行了分析和比较.结果表明采用2种表面修饰方法得到的羧甲基香菇多糖修饰的聚乳酸材料的亲水性、血液相容性以及对大肠杆菌抗菌活性得到改善.与化学接枝方法相比,经过羧甲基香菇多糖与壳聚糖层层自组装修饰的聚乳酸材料具有更好的亲水性、血液相容性和抗菌活性.     

相分离法制备聚碳酸酯/聚乳酸复合微球与调控

聚碳酸酯(PC)、聚乳酸(PLA)及三氯甲烷(CHCl_3)混合作为油相,聚乙烯醇(PVA)溶液作为水相,通过相分离法制备PC/PLA复合微球。研究CHCl_3浓度、水油比、PVA质量分数及PC/PLA质量配比对形成的PC/PLA复合微球形貌、结构的影响。实验结果表明:最佳的相分离实验条件为CHCl_3浓度为2g/mL、水油比为4∶1、PVA质量分数为1%及PC/PLA质量配比为1/1时通过SEM观察到粒径分布均匀、规则、光滑的复合微球。在适宜的条件下,PC和PLA分子链间作用力相当,扩散能力强,协同一致地结晶,促进成核-结晶而制备PC/PLA复合微球。     

反应性梳状聚乙二醇改性聚酯薄膜表面及其内皮细胞相容性的研究

以高密度梳状PEG(CPEG)作为表面改性材料, 将PEG末端羟基转化为醛基, 将梳状PEG和线形PEG固定在氨基化的PET膜表面, 并利用表面的反应性醛基进一步固定了氨基酸和整合素配体多肽片段RGD多肽. 红外光谱、 接触角和X射线光电子能谱(XPS)测定结果表明, 该法可有效地固定氨基酸和多肽, 获得模拟细胞膜中多糖-蛋白质复合物结构的特异性功能表面. 对两种不同结构的PEG细胞培养实验结果表明, CPEG比线形PEG(LPEG)具有更好的抗非特异粘附性. 此外, CPEG比LPEG具有更多的活性反应基团, 用PEG末端活性的醛基固定整合素配体多肽片段RGD, 可有效地诱导材料表面的内皮细胞化, 改善材料的细胞相容性.     

基于天然高分子基元的阻隔层对磁性载药聚乳酸微球的控释作用

利用层层组装技术构建了基于天然高分子壳聚糖和海藻酸钠的阻隔层, 并研究了该阻隔层对磁性载药聚乳酸微球的药物释放作用. 实验结果表明, 阻隔层能够有效抑制模型药物的突释, 具有延缓药物释放的效果. 具有阻隔层的磁性载药体系具有药物释放平缓和生物相容性高等特点, 是理想的磁靶向载药体系.     

聚乙二醇接枝聚乳酸的自组装纳米微球的制备及性能

对制备的新型聚乙二醇(PEG)接枝聚乳酸(PLA)在水中的自组装性能进行研究, 探讨其作为纳米药物载体的可行性和稳定性. 目测法得到其溶解度为(2.16～4.32)×10^－2 mg•mL^－1; 荧光法得到聚合物的临界胶束浓度为1.12×10^－3 mg•mL^－1; 透射电子显微镜观察显示该聚合物在水中的自组装聚集体为纳米级球形; 动态激光光散射测试微球的粒径和Zeta电位发现, 在微球的制备过程中, 聚合物的亲/疏水性比例、水相介质及水溶液的pH值对它影响显著; 而制备后, 稀释和冷冻对它无显著影响, 改变微球的环境pH值至酸性, 出现聚集, 至碱性无影响. 研究结果显示, 该聚合物在水和磷酸钠盐缓冲液中可形成稳定的纳米微球, 通过微球的制备条件和存在环境可控制其粒径和Zeta电位, 因此根据应用需要, 通过控制其粒径和Zeta电位, 可能提高微球的在体血液循环时间并实现靶向缓释.     

生物可降解5-氟尿嘧啶载药微球的制备及性能研究

5-氟尿嘧啶(5-Fu)为水溶性嘧啶类抗代谢药,是治疗实体肿瘤的首选药物．但5-Fu毒性很大,血浆中停留半衰期t1／2仅为10～20min．为了减少氟尿嘧啶的毒副作用并提高药物利用率,可以将其制成聚合物载药微球．聚酯类高分子是较为常用的生物降解型药物载体材料,其中聚乳酸(PLA)及其共聚物具有良好的生物相容性及生物可降解性,常被广泛应用于药物缓释材料,     

Hydrolysis and biomineralization of porous PLA microspheres and their influence on cell growth

Poly(lactic acid) (PLA) microspheres have great potential in bone tissue engineering. However, their applications have been limited by surface and bulk properties such as hydrophobicity, lack of cell recognition sites and acidic degradation products. Apatite is a mineral which can effectively promote the adhesion and growth of bone cells. In this study, the bonelike mineral, carbonate apatite, was successfully used to functionalize porous PLA microspheres by a biomimetic mineralization method. To improve apatite formation, porous PLA microspheres were first selectively hydrolyzed in NaOH solution to increase the density of polar anionic groups on the surface, and then immersed in simulated body fluid for biomineralization. The morphology, composition, and phase structure of bioactive mineral grown on the original and hydrolyzed PLA microspheres were analyzed and compared quantitatively. The results showed that the hydrolysis which took place on the PLA microspheres enhanced the nucleation and growth of apatite. MG-63 cells attached well and spread actively on the mineralized PLA microspheres, indicating their strong potential in bone tissue engineering.     

The influence of chitosan on in vitro properties of Eudragit RS microspheres

Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using acetone/liquid paraffin solvent system and their properties were compared with Eudragit RS microspheres without chitosan, prepared in our previous study. Different stirring rates were applied (400-1200 rpm) and drug content, Higuchi dissolution rate constant, surface and structure characteristics of the microspheres were determined for each size fraction. An increase in average particle size with a reduction of stirring rate appeared in limited interval in both series. The average particle size of microspheres without chitosan, prepared at the same stirring rate, was smaller. Pipemidic acid content increased with increasing fraction particle size, but not with increasing stirring rate as it was observed for microspheres without chitosan. We presume that high pipemidic acid content in larger microspheres is a consequence of cumulation of undissolved pipemidic acid particles in larger droplets during microspheres preparation procedure. Pipemidic acid release was faster from microspheres with chitosan and no correlation between Higuchi dissolution rate constant and stirring rate or fraction particle size was found, though it existed in the system without chitosan. Structure and surface characteristics of microspheres observed by scanning electron microscope (SEM) were not changed significantly by incorporation of chitosan. But in contrast with microspheres without chitosan, the surface of chitosan microspheres was more porous after three hours of dissolution. It is supposed that the influence of particle size fraction and stirring rate on release characteristics is expressed to a great extent through porosity and indirectly through total effective surface area, but the incorporation of highly soluble component i.e. chitosan salt hides these effects on drug release. In conclusion, changes in biopharmaceutical properties due to varying stirring rate and fraction particle size exhibited the same direction as those reported for the microspheres without chitosan, although they are less expressed because of increased experimental variability, likely caused by chitosan.     

Chromatographic studies of mitomycin C degradation in albumin microspheres

Serum albumins and polylactic acid (PLA) have been used as bioerodable polymers in the preparation of drug-containing microspheres for parenteral drug delivery. The albumin microsphere may be prepared via either chemical cross-linking or heat denaturation of the protein. Heat-denatured albumin microspheres containing mitomycin C (MMC) have been used in pre-clinical and clinical investigations. Due to the high reactivity of MMC as a bifunctional alkylating agent, a study on the stability of MMC in the albumin and PLA microspheres has been carried out using a high-performance liquid chromatographic (HPLC) method. Human serum albumin (HSA) microspheres were prepared using an emulsion method via either heat denaturation at 120 or 170 degrees C or the use of 0.5 M biacetyl as a cross-linking agent. The PLA microspheres were prepared by an emulsion method at 55 degrees C. HPLC analysis of the HSA microspheres showed that about 37% of MMC was converted to 2,7-diaminomitosene derivatives in microspheres prepared by heat denaturation at 120 degrees C. The degradation increased to 82% when the microspheres were prepared with a denaturation temperature of 170 degrees C. The use of biacetyl as a cross-linking agent in the preparation of HSA microspheres resulted in a complete degradation of the incorporated MMC. Biacetyl was found to interact with MMC leading to the formation of 7-aminomitosene derivatives. In contrast to the albumin system, MMC may be incorporated into PLA microspheres without degradation.     

Osteoblast culture on bioerodible polymers: studies of initial cell adhesion and spread

The development of systems for the growth of osteoblasts on bioerodible polymeric matrices was explored. Three classes of bioerodible polymers were studied as possible matrix supports for osteoblast growth: the poly(anhydrides), poly(phosphazenes) and poly(lactic acid/glycolic acid) copolymers. Neonatal calvarial cells from Sprague–Dawley rats were seeded onto polymer disks at a density of 1 × 10⁴ cells/cm². Initial attachment and spreading, rate of growth and morphology were determined, and retention of osteoblast-like phenotype was assessed through measurements of alkaline phosphatase activity in the presence and absence of 1,25(OH)₂ vitamin D3. All results were considered relative to tissue culture polystyrene. Cells were found to attach to all polymers at 8 hr post-seeding. By 24 hr, cell numbers on all polymers were found to be decreased, except for poly(lactic acid/glycolic acid). Rat calvarial osteoblasts seeded on poly-(lactic acid/glycolic acid) reached confluency and retained their phenotype. Successful construction of viable osteoblast–bioerodible polymer composite materials, as presented in our study, may find their usefulness as grafts for atrophic non-unions of bone, for healing craniofacial and other defects and for use as prosthetic implants or coatings. Composite systems of osteoblast cultures may also find their usefulness in furthering our understanding of bone differentiation, maturation and metabolism in a matrix environment.     

Effects of acidic catalysts on the microstructure and biological property of sol–gel bioactive glass microspheres

Sol–gel bioactive glasses have been developed for bone tissue regeneration and drug delivery systems as they have the unique mesoporous structure and high bioactivity in vitro. To develop more reliable drug delivery and bone tissue repair systems, it is necessary to control the morphology and microstructure of bioactive glasses. For this purpose, bioactive glass microspheres (BGMs) were prepared by a sol–gel co-template technology using acids as catalysts. We studied the effects of different acids (citric acid, lactic acid and acetic acid) on the microstructure and apatite-forming bioactivity of BGM. The apatite-forming bioactivity was carried out in simulated body fluid (SBF). The microstructure and apatite-forming bioactivity of BGMs were characterized by various methods. Results showed that acetic acid had little effect on the structure and bioactivity of BGMs. Differently, the morphology and microstructure of BGMs could be controlled by changing citric acid and lactic acid concentrations. In vitro bioactivity test indicated that citric acid and lactic acid derived BGMs possessed the better apatite-forming capacity than that derived by acetic acid.     

阴离子型淀粉微球的合成及性能研究

本文以淀粉或淀粉衍生物为原料，ＰＯＣｌ３为交联剂，采用逆相悬浮交聚合技术合成了阴离子淀粉微球。以淀粉为基质中性微球不原料，用Ｎａ３Ｐ３Ｏ９作交联剂进行二次交联和阴离子化，得到另一种阴离子型淀粉微球，研究了两种微球的表观形态，粒径分布、溶胀性和吸附载药性能。     

Bulk and surface modifications of polylactide

This article reviews various methods of modifying the bulk and surface properties of poly(lactic acid) (PLA) so that the polymer may be used as a drug carrier in a drug delivery system (DDS) and as a cell scaffold in tissue engineering. Copolymerization of lactide with other lactone-type monomers or monomers with functional groups such as malic acid, copolymerization of lactide with macromolecular monomer such as poly(ethylene glycol) (PEG) or dextran, as well as blending polylactide and natural derivatives and other methods of bulk modification are discussed. Surface modifications of PLA-type copolymers, such as surface coating, chemical modification, and plasma treatment are described. Cell culture technology proves the efficiency of bulk and surface modification and the potential application of PLA in tissue engineering.     

Superiority of poly(L-lactic acid) microspheres as dermal fillers

The demand for injectable dermal filler has unde rgone significant growth with the rapid development of the beauty industry.Poly(lactic acid)(PLA) as a benefit of excellent biocompatibility and long-term promotion of collagen regeneration has been favored as a commonly used filler.However,the effects of chirality and particle size of PLA on the efficacy of dermal filler have not been studied.In this study,we prepared three kinds of microspheres(MSs) consisting of poly(D-lactic acid)(PDLA MS),poly(L-lactic acid)(PLLA MS),or meso-PLA(PDLLA MS)at 5,10 and 20 μmto reveal the different biological functions as dermal filler.Following intradermal injection into guinea pig,it was found that PLLA MS induced the slightest inflammation,and the level of pro-inflammatory cytokine IL-1β induced by PLLA MS is only 0.3 or 0.7-fold of that induced by PDLA or PDLLA MS,respectively.More importantly,PLLA MS significantly stimulated the regeneration of collagen,which was 1.4 or 1.1 times higher than those stimulated by PDLA MS or PDLLA MS,respectively.The size of PLA MSs did not affect the levels of inflammation and collagen regeneration.The results confirmed the superiority of PLLA as a dermal filler.     

Preparation of a thermosensitive and biodegradable microgel via polymerization of macromonomers based on diacrylated Pluronic/oligoester copolymers

A novel biodegradable and thermosensitive hydrogel microparticle was prepared via suspension polymerization of a kind of block copolymer macromonomers. According to the molecular design, the macromonomer is composed of a thermosensitive triblock copolymer poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) and two oligomers of biodegradable polyester such as oligo(lactic acid) or oligo(ε-caprolactone), and end-capped with acryloyl groups. Microgels were obtained by inverse suspension polymerization of the macromonomer aqueous droplets initiated by a redox initiator. Thermosensitivity and in vitro biodegradation of the resultant microgels were confirmed. The gel microparticles in an aqueous solution were swollen at low temperature and shrunken at high temperature (human body temperature). Degradation rate could be adjusted by controlling the composition and the degree of polymerization of oligoester. Thus, the microgels exhibit combinatory and tunable properties.