Shenoy D B, D'Souza R J, Udupa N
Dr T.M.A. Pai Pharmaceutical Research Centre, College of Pharmaceutical Sciences, Manipal 576 119, Karnataka, India.
J Microencapsul. 2002 Jul-Aug;19(4):523-35. doi: 10.1080/02652040210141084.
In the present investigation, a poly(DL-co-glycolide) (PLGA)-based, microspheric depot system for bleomycin (BLM) has been formulated, and the same has been evaluated in-vivo in C57BL/6J mice bearing transplantable melanoma B16F1 murine solid tumour. The microparticulate delivery systems were formulated employing a water-in-oil-in-water (W/O/W) emulsion-solvent evaporation technique and characterized in-vitro. The microspheres were injected subcutaneously to form a drug depot at the site of injection in mice bearing experimental tumours and the drug was continuously infused into the systemic circulation with progressive biodegradation. The drug-loaded microspheres exhibited improved pharmacodynamic efficacy, as evidenced by retarded tumour growth kinetics. Preliminary pharmacokinetic studies illustrated controlled release of the drug into the systemic circulation over the study period to exert an anti-neoplastic action. These studies demonstrated the feasibility of employing a PLGA-based microparticulate system as an effective biodegradable, injectable, depot-forming therapeutic system for long-term administration of anti-neoplastic agents.
在本研究中，已制备了一种基于聚（DL-丙交酯-乙交酯）（PLGA）的博来霉素（BLM）微球长效注射系统，并在携带可移植性黑色素瘤B16F1小鼠实体瘤的C57BL/6J小鼠体内进行了评估。采用水包油包水（W/O/W）乳液溶剂蒸发技术制备了微粒给药系统，并进行了体外表征。将微球皮下注射到荷实验性肿瘤的小鼠体内，在注射部位形成药物储库，药物随着微球的逐步生物降解持续输注到体循环中。载药微球表现出更好的药效学效果，肿瘤生长动力学延迟证明了这一点。初步药代动力学研究表明，在研究期间药物可控制释放到体循环中以发挥抗肿瘤作用。这些研究证明了采用基于PLGA的微粒系统作为一种有效的可生物降解、可注射、形成储库的治疗系统用于长期给药抗肿瘤药物的可行性。
