Paclitaxel loaded poly(L-lactic acid) microspheres: properties of microspheres made with low molecular weight polymers

Microspheres were prepared from poly(L-lactic acid) polymers having molecul ar weights between 500 and 50k g/mol. The polymers were synthesized using t wo 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 po lymer 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, c ompared to 25 to 55 degreesC for PLLA-LA polymers. Changes in Tm and enthal py of melting with increasing molecular weight were similar for both PLLA-L A 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 pro perties as molecular weight increased. As the molecular weight increased fr om 2k to 50k g/mol the amount of drug released from microspheres over 14 da ys decreased From 76 to 11% of the initial drug load. The release profiles were consistent with a diffusion controlled mechanism provided a two-compar tment model was employed. According to this model, the total amount of 'ava ilable' drug (compartment 1) was released by diffusion in 14 days while the remainder (compartment 2) was confined within the polymeric matrix and cou ld not diffuse out at a measurable rate. Following the in vitro release stu dy, 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.