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  • Title: The characterization of paclitaxel-loaded microspheres manufactured from blends of poly(lactic-co-glycolic acid) (PLGA) and low molecular weight diblock copolymers.
    Author: Jackson JK, Hung T, Letchford K, Burt HM.
    Journal: Int J Pharm; 2007 Sep 05; 342(1-2):6-17. PubMed ID: 17555895.
    Abstract:
    Paclitaxel-loaded biodegradable drug delivery systems manufactured from poly(lactic-co-glycolic acid) (PLGA) are known to release the drug at extremely slow rates. The objective of this study was to characterize paclitaxel-loaded microspheres composed of blends of PLGA with low molecular weight ampipathic diblock copolymers. The encapsulation and release of a series of poly(epsilon-caprolactone) (PCL)- or poly(D,L-lactic acid) (PDLLA)-co-methoxypolyethylene glycol (MePEG) diblock copolymers was measured using quantitative gel permeation chromatography. Polymeric miscibility was determined by glass transition temperature measurements using differential scanning calorimetry and paclitaxel release was measured using HPLC methods. The PCL- and PDLLA-based diblock copolymers encapsulated at high efficiency and were miscible in PLGA microspheres (30-120m microm size range). The burst phase of paclitaxel release was increased up to 20-fold by the inclusion of diblock copolymers in PLGA microspheres. Approximately 10% of the more hydrophobic PCL-based copolymers released from the microspheres in a short burst over 3 days followed by very slow release over the following 10 weeks. Only the PDLLA-based copolymer released from the PLGA microspheres in a controlled manner over 10 weeks. All microspheres containing PEG were found to have more hydrophilic surfaces (as measured by contact angle) with improved biocompatibility (reduced neutrophil activation) compared to PLGA only microspheres. These results indicate that low molecular weight polyester-based diblock copolymers may be effectively encapsulated in PLGA microspheres to increase paclitaxel release (probably through a micellization process) and improve biocompatibility.
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