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  • Title: Paclitaxel-loaded poly(L-lactic acid) microspheres 3: blending low and high molecular weight polymers to control morphology and drug release.
    Author: Liggins RT, Burt HM.
    Journal: Int J Pharm; 2004 Sep 10; 282(1-2):61-71. PubMed ID: 15336382.
    Abstract:
    Microspheres were prepared from paclitaxel and binary polymer blends incorporating 1, 3, 40k and 100k g/mol PLLA. Thermal analysis was performed by DSC and in vitro paclitaxel release profiles were determined at 37 degrees C in phosphate buffer using an HPLC assay. In microspheres made with 3k/40k PLLA blends, the glass transition (Tg), crystallinity and melting temperature (Tm) all decreased with an increasing proportion of low molecular weight polymer in the blend. Similar trends were observed for 1k/100k blends. Tm values ranged from 175 to 110 degrees C and Tg values between 66 and 37 degrees C. However, for 1k/100k blends, melting point depression was linearly dependent on blend composition when plotted as 1/Tm = 0.000109 x (%1k in blend) + 0.0223, R2 = 0.97. A similar plot with data from the 3k/40k system yielded a non-linear relationship. Furthermore, the decrease in Tg for both 1k/100k and 3k/40k blends followed the Fox equation, although experimental values were consistently 1-2 degrees C above predicted values. Paclitaxel release from microspheres made with a 1k/100k blend occurred in four distinct phases: a burst phase (day 0), a slower phase, a second burst (day 35) and a second slower phase (until day 70). The second burst coincided with visible degradation of the microspheres. Blends of low and high molecular weight PLLA display thermal properties indicating that 1k g/mol PLLA behaves as a diluent when blended with 100k g/mol PLLA, being excluded from the crystalline domains in the polymer matrix. In contrast, 3k g/mol PLLA is incorporated in both amorphous and crystalline regions of the polymer blend. Paclitaxel release profiles from 1k/100k PLLA microspheres demonstrate a multiphase profile due to the effects of both diffusion and degradation controlled release mechanisms.
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