Double-walled microspheres for the sustained release of a highly water soluble drug: characterization and irradiation studies
Double-walled microspheres for the sustained release of a highly water soluble drug: characterization and irradiation studies
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DOI：
10.1016/s0168-3659(02)00235-3
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发表时间：
2002-10-30
影响因子：
10.8
通讯作者：
Wang, CH
中科院分区：
文献类型：
--
作者：
Lee, TH;Wang, JJ;Wang, CH
制备了具有可生物降解聚l -乳酸（PLLA）外壳和聚D， l -乳酸-羟基乙酸（PLGA）核的复合双壁微球，核内包裹有高水溶性的依替硝唑作为固体晶体。本文讨论了该类微球的性质、体外释放及辐照对其的影响。通过改变聚合物的质量比，可以制造出可预测的壳和芯尺寸，并用于调节释放速率。根据聚合物对在乙酸乙酯中的不同溶解度，设计了一种直接、简便的方法来测定壳核聚合物的组成。基于溶解度参数的分布理论解释了为什么高亲水性的依他硝唑倾向于一致地分布到更亲水的聚合物上。正常双壁样品在初始时滞后10天内释放约80%的药物，而辐照双壁样品的缓释持续时间超过3周。虽然缓释时间短于治疗所需的6-8周，但由于其初始爆发量低于5%，并且可以控制时间滞后，因此可以将这些微球与传统微球一起施用，从而产生脉动释放或新型释放。还研究了辐照的影响，以确定这些双壁微球作为放射治疗联合使用的输送装置的适用性。研究发现，典型的治疗剂量为50 Gy，对聚合物及其释放曲线没有明显影响，而灭菌剂量为25 kGy，降低了玻璃化转变温度和结晶熔点，间接表明分子量降低。这加速了聚合物的降解，从而释放了药物。(C) 2002 Elsevier Science B.V.版权所有
Composite double-walled microspheres with biodegradable poly(L-lactic acid) (PLLA) shells and poly(D,L-lactic-co-glycolic acid) (PLGA) cores were fabricated with highly water-soluble etanidazole entrapped within the core as solid crystals. This paper discusses the characterization, in vitro release and the effects of irradiation on this class of microsphere. Through the variation of polymer mass ratios, predictable shell and core dimensions could be fabricated and used to regulate the release rates. A direct and simple method was devised to determine the composition of the shell and core polymer based on the different solubilities of the polymer pair in ethyl acetate. A distribution theory based on solubility parameter explains why highly hydrophilic etanidazole has the tendency to be distributed consistently to the more hydrophilic polymer. Release profiles for normal double-walled samples have about 80% of drug released over 10 days after the initial time lag, while for irradiated double-walled samples, the sustained release lasted for more than 3 weeks. Although sustained release was short of the desired 6-8 weeks required for therapy, a low initial burst of less than 5% and time lags that can be manipulated, allows for administration of these microspheres together with traditional ones to generate pulsatile or new type of releases. The effects of irradiation were also investigated to determine the suitability of these double-walled microspheres as delivery devices to be used in conjunction with radiotherapy. Typical therapeutic dosage of 50 Gy was found to be too mild to have noticeable effects on the polymer and its release profiles, while, sterilization dosages of 25 kGy, lowered the glass transition temperatures and crystalline melting point, indirectly indicating a decrease in molecular weight. This accelerated degradation of the polymer, hence releasing the drug. (C) 2002 Elsevier Science B.V. All rights reserved.