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  • Title: Preparation of bleomycin A2-PLGA microspheres and related in vitro and in vivo studies.
    Author: Zhang H, Gao Y, Lv W, Jiao C, Duan M, Liu H, Han B.
    Journal: J Pharm Sci; 2011 Jul; 100(7):2790-800. PubMed ID: 21344412.
    Abstract:
    The goals of these studies were to prepare bleomycin (BLM) A(2)-poly(lactic-co-glycolic acid) (PLGA) microspheres and to investigate their in vitro release, pharmacokinetics, pharmacodynamics, and toxicology of this product. Long-acting BLM A(2)-PLGA microspheres were prepared using multiple emulsion solvent evaporation, and the related characteristics of the microspheres were investigated. The prepared microspheres were administered to dogs via intramuscular injection. The plasma concentration of BLM A(2) in dogs was detected using liquid chromatography-mass spectrometry. The pharmacodynamics of BLM A(2)-PLGA microspheres were investigated in a golden hamster model. The acute and chronic toxicities were investigated in a rat model. The inductive effects of BLM microspheres versus a conventional formulation on pulmonary injuries were compared in a mouse model. BLM A(2)-PLGA microspheres were released stably over 20 days and exhibited a significant inhibition of oral squamous carcinoma. The acute toxicity study suggested that doses up to 128 mg/kg were acceptable, and the chronic toxicity study showed no significant chronic toxicity. The study in mice showed less pulmonary toxicity with BLM microsphere formulation compared with the conventional formulation. As a novel microsphere drug formulation, BLM A(2)-PLGA microspheres showed a significant slow-release effect. These data may provide a new clinical medication option for patients with oral cancer.
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