Paclitaxel loaded poly(L-lactic acid) microspheres: properties of microspheres made with low molecular weight polymers
Paclitaxel loaded poly(L-lactic acid) microspheres: properties of microspheres made with low molecular weight polymers
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DOI：
10.1016/s0378-5173(01)00690-1
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发表时间：
2001-07-03
影响因子：
5.8
通讯作者：
Burt, HM
中科院分区：
文献类型：
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作者：
Liggins, RT;Burt, HM
微球由分子量在500和50 k g/mol之间的聚（L-乳酸）聚合物制备。使用两种引发剂分子，L-乳酸低聚物（PLLA-LA）或硬脂醇（PLLA-SA）合成聚合物。对于PLLA-LA和PLLA-SA聚合物，玻璃化（Tg）和熔融（Tm）转变温度和熔融焓都随着聚合物分子量的增加而增加。当分子量从500增加到10 k g/mol时，PLLA-SA显示出最大的Tg变化（-13至54 ℃），而PLLA-LA聚合物的Tg变化为25至55 ℃。对于PLLA-LA和PLLA-SA，Tm和熔化焓随分子量增加的变化相似。紫杉醇释放从30%开始，随着分子量的增加，尺寸范围为50-90 μ m的紫杉醇负载微球受到聚合物性质的这些变化的影响。随着分子量从2k增加到50 k g/mol，14天内从微球释放的药物量从初始载药量的76%下降到11%。采用二室模型，释放曲线与扩散控制机制一致。根据该模型，“可用”药物的总量（隔室1）在14天内通过扩散释放，而剩余部分（隔室2）被限制在聚合物基质内，并且不能以可测量的速率扩散出去。在体外释放研究之后，由2k-10 k g/mol聚合物制成的微球显示出显著的崩解迹象，而50 k g/mol聚合物微球保持完整。(C)2001 Elsevier Science B. V.保留所有权利。
Microspheres were prepared from poly(L-lactic acid) polymers having molecular weights between 500 and 50k g/mol. The polymers were synthesized using two initiator molecules, L-lactic acid oligomer (PLLA-LA) or stearyl alcohol (PLLA-SA). For both PLLA-LA and PLLA-SA polymers, glass (Tg) and melting (Tm) transition temperatures and enthalpy of melting all increased as the polymer molecular weight increased. PLLA-SA showed the greatest change in Tg (-13 to 54 degreesC) as molecular weight increased from 500 to 10k g/mol, compared to 25 to 55 degreesC for PLLA-LA polymers. Changes in Tm and enthalpy of melting with increasing molecular weight were similar for both PLLA-LA and PLLA-SA. Paclitaxel release From 30%, paclitaxel loaded microspheres in the size range of 50-90 mum was affected by these changes in polymer properties as molecular weight increased. As the molecular weight increased from 2k to 50k g/mol the amount of drug released from microspheres over 14 days decreased From 76 to 11% of the initial drug load. The release profiles were consistent with a diffusion controlled mechanism provided a two-compartment model was employed. According to this model, the total amount of 'available' drug (compartment 1) was released by diffusion in 14 days while the remainder (compartment 2) was confined within the polymeric matrix and could not diffuse out at a measurable rate. Following the in vitro release study, microsphere made from 2k-10k g/mol polymers showed significant signs of disintegration whereas 50k g/mol polymer microspheres remained intact. (C) 2001 Elsevier Science B.V. All rights reserved.