Synthesis of the Biomimetic Polymer: Aliphatic Diamine and RGDS Modified Poly(d,l-lactic acid)

A novel poly（d, /-lactic acid） （PDLLA） based biomimetic polymer was synthesized by grafting maleic anhydride, butanediamine and arg-gly-asp-ser （RGDS） peptides onto the backbone of PDLLA, aiming to overcome the acidity and auto-accelerating degradation of PDLLA during degradation and to improve its biospecificity and biocompatibility. The synthetic copolymer was characterized by FTIR, ^13C NMR and amino acid analyzer （AAA）.

Synthesis and Characterization of Chitosan-g-poly- (D, L-lactic acid) Copolymer

Biodegradable chitosan-g-poly (D, L-lactic acid) copolymers were prepared via two methods. (1) The lactide was grafted onto hydroxyl groups of chitosan by using macromolecular initiator sodium of trimethylsilyl-chitosan, (2) poly (D,L-lactic acid)(PLA) with low molecular weight can be linked to the amino group by coupling activated PLA to trimethylsilyl-chitosan. Two graft copolymers had hydrophilic-hydrophobic character and can be applied as carriers for drug delivery.

Microwave-assisted Polymerization of D,L-Lactide with Stannous Octanoate as Catalyst

Poly (lactic acid) (PLA) was synthesized by microwave-assisted ring-opening polymerization of D, L-lactide with stannous octanoate (SnOct(2)) as catalyst. Its weight-average molar mass (M-w) ranged from 39000 to 67000 and the polydispersity index from 1.3 to 1.7. The polymerization rate was much faster than that of the conventional thermal polymerization. A degradation of newly formed PLA in reaction mixture by microwave irradiation was observed.

Preparation and Degradation Characteristics of Poly(d,1-laetide) Composite Films

PDLLA/CHI/β-TCP/NGF composite films were prepared by a solvent evaporation method. The degradation characteristics of the poly （d, l-lactide） composite films were studied in vitro and in vivo. The acidity produced by poly （d, l-lactide） materials was not obvious. Adding chitosan and β-TCP can relieve the acidity problem and improve strength performance of films. The NGF has influences on the degradation characteristics of films. It is verified that PDLLA/CHI/β-TCP/NGF composite films prepared by solvent evaporation method have excellent degradation characteristics. It can be used as a perfect biomaterial for repairing nerve injuries.

The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid)in rat

Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid)(PEG-PLA)is a typical amphiphilic di-block copolymer widely used as a nanoparticle carrier(nanocarrier)in drug delivery.Understanding the in vivo fate of PEG-PLA is required to evaluate its overall safety and promote the development of PEG-PLA-based nanocarrier drug delivery systems.However,acquiring such understanding is limited by the lack of a suitable analytical method for the bioassay of PEG-PLA.In this study,the pharmacokinetics,biodistribution,metabolism and excretion of PEG-PLA were investigated in rat after intravenous administration.The results show that unchanged PEG-PLA is mainly distributed to spleen,liver,and kidney before being eliminated in urine over 48 h mainly(>80%)in the form of its PEG metabolite.Our study provides a clear and comprehensive picture of the in vivo fate of PEG-PLA which we anticipate will facilitate the scientifc design and safety evaluation of PEG-PLA-based nanocarrier drug delivery systems and thereby enhance their clinical development.

生物可降解型石杉碱甲微球的研究

目的 制备能够在一个月甚至更长时间内缓释石杉碱甲的注射型生物可降解微球。方法 选用端基不封口的PLA或PLGA、采用简单的O／W乳化溶剂挥发法制备微球；详细考察了微球的形态、粒径及分布、载药量和包封率；用透析法测定微球的体外药物释放曲线。结果 成功地将石杉碱甲包裹入聚合物中；制得的微球表面光滑，但不同材料制得的微球内部结构不同，粒径全部小于250gm，粒径分布较窄，载药量的质量分数在4％～6．5％内，包封率的质量分数在45％～65％内，比用端基封口的聚合物制备的微球包封率高15倍以上；体外释药试验表明，载有石杉碱甲的3种微球能够在5～7周内缓释药物。结论 利用生物可降解型微球缓释石杉碱甲是可行的。

伊维菌素聚乳酸微球制备条件的优化及药物含量测定

用乳化溶剂挥发法制备了伊维菌素（ＩＶＭ）聚乳酸（ＰＬＡ）微球试验采用Ｌ１８（３７）正交设计，以微球粒径分布为主要优选水平，结合微球收率和包裹率，筛选出最佳制备条件：连续相为２０ｇ·Ｌ－１的聚乙烯醇（ＰＶＡ）水溶液；分散相为ＰＬＡ（Ｍｒ８２万，投量２０ｇ）和ＩＶＭ原料药（０６７或１００ｇ）溶于２５ｍＬ二氯甲烷；搅拌速度为４５０ｒ·ｍｉｎ－１，在３７℃恒温下搅拌１２ｈ挥干二氯甲烷，过滤收集微球所得微球干燥后呈白色粉末状，微球平均收率为８７９０％±１１６％［ｗ（ＩＶＭ）理论值为２５０％］和８８．３３％±２．６８％［ｗ（ＩＶＭ）理论值为３３．３％］采用溶解沉淀法，以ＲＰ－ＨＰＬＣ－ＵＶ法测定微球中药物含量：以二氯甲烷和甲醇（１∶９）为溶媒，可完全沉淀聚合物；药峰分离完全，无干扰峰；

低相对分子质量聚乳酸及其与壳聚糖的共混为载体的药物控释研究

以两种低黏均相对分子质量(Mη=3 595和10 306)聚乳酸及其与壳聚糖按5∶1,10∶1,20∶1,40∶1质量比共混为载体,用熔融法制备了吡虫啉控释制剂;用体外实验测定了制剂中吡虫啉的释放动力学;通过测定释放过程中释放介质水的pH,初步考察了基体的降解性能;通过测定释放实验结束时制剂残留质量,考察了基体的溶蚀性能,初步探讨了释放机理。结果表明,低相对分子质量聚乳酸及其与壳聚糖共混材料为载体,可以用于吡虫啉的控制释放,呈现扩散和溶蚀共同控制的缓慢释放,和溶蚀控制的快速释放两阶段释放规律。提高聚乳酸的相对分子质量可以减缓吡虫啉的释放,使释放特征发生从初期的快速释放和后期的缓慢释放,到初期缓慢释放和随后的快速持续释放的转变。降低聚乳酸相对分子质量或在基体中加入壳聚糖,可加大基体的溶蚀,使溶蚀控制的吡虫啉快速释放阶段提前。在Mη=10 306的聚乳酸中加入不同质量比的壳聚糖,可使释放介质水的pH约为中性,在117-336 h内调节快速释放开始时间,在228-445 h内调节释药中值时间。这种聚乳酸/壳聚糖共混载体可望在多功能型种子处理控释制剂上获得应用。

Enhanced mechanical properties of linear segmented shape memory poly（urethane-urea） by incorporating flexible PEG400 and rigid piperazine

The goal of this study is to design and synthesize a linear segmented shape memory poly（urethane-urea） （SMPUU） that possesses near-body-temperature shape memory temperature （Ttran） and enhanced mechanical properties by incorporating flexible poly（ethylene glycol） 400 （PEG400） to form poly（D,L-lactic acid）-based macro- diols （PDLLA-PEG400-PDLLA） and then rigid piperazine （PPZ） as a chain extender to form the desired SMPUUs （PEG400-PUU-PPZ）. PEG400 increased Mn while maintaining a lower Tg of PDLLA-PEG400-PDLLA, which together with PPZ improved the mechanical properties of PEG400-PUU-PPZ. The obtained optimum SMPUU with enhanced mechanical properties （O＇y = 24.28 MPa; zf = 698%; Uf = 181.5 MJIm3） and a Tg of 40.62~C exhibited sound shape memory properties as well, suggesting a promising SMPUU for in vivo biomedical applications.

复合催化剂催化D,L-丙交酯的合成实验研究

D，L-丙交酯（DLLA）是合成聚乳酸的关键中间体，其收率直接影响到聚乳酸的收率。采用氯化亚锡／氧化锌做为复合催化剂，研究合成丙交酯的反应条件，提高了丙交酯的收率。实验结果表明：当采用复合催化剂，氯化亚锡：氧化锌的质量比=4：1，其用量为乳酸质量的1％，在减压条件下（20kPa），130—140℃脱水3．5h，馏出温度为220℃时，可使DLLA收率最大为36．0％。

Cellulose Nanocrystals-mediated Phase Morphology of PLLA/TPU Blends for 3D Printing

Incorporation of nanoparticles into polymer blend to obtain finely dispersed morphology has been considered as an effective strategy to prepare nanocomposites. Owing to the renewable and degradable characters, cellulose nanocrystals(CNCs) have been proposed to tailor the phase morphology of poly(L-lactic acid)(PLLA) blend for producing high-performance fused deposition modeling(FDM) consumables. However,the main challenge associated with the ternary systems is the dispersion of the highly hydrophilic CNCs in non-polar PLLA blend by industrial melt blending without involving solution. Herein, with poly(vinyl acetate)(PVAc) modified CNCs powder(a mixture of PVAc grafted from CNCs and PVAc homopolymer latex), the selective dispersion of CNCs in PLLA has been achieved by simple melt processing of PLLA/TPU(polyether polyurethane)/CNCs blend. This results in the ultra-fine TPU droplets at nanoscale in PLLA and improves the melt processibility of composites in FDM due to the decreased viscosity ratio of the dispersed/matrix and the enhanced melt elasticity of PLLA. Combined with the intensive shear and continuous stretch effect during FDM, aligned TPU nanofibers(TNFs) were in situ formed along the elongational flow direction during deposition, which in turn contributed to the improvement of PLLA/TPU/CNCs with 5 wt% filler loading in tensile ductility by 418%, inter-layer adhesion strength and notched impact toughness by 261% and 210%, respectively, as well as achieved good dimensional accuracy and very fine surface quality.