Poly(DL-lactide-co-glycolide) microporous microsphere- based depot formulation of a peptide-like antineoplastic agent D. B. SHENOY*, R. J. D’SOUZA and N. UDUPA Dr T.M.A. Pai Pharmaceutical Research Centre, College of Pharmaceutical Sciences, Manipal 576 119, Karnataka, India (Received 29 September 2001; accepted 18 January 2002 ) In the present investigation, a poly(dl-co-glycolide) (PLGA)-based, micro- spheric 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 micro- spheres exhibited improved pharmacodynamic ecacy, as evidenced by retarded tumour growth kinetics. Preliminary pharmacokinetic studies illu- strated 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 eective biodegradable, injectable, depot-forming therapeutic system for long-term administration of anti-neoplastic agents. Keywords: Bleomycin, PLGA, microspheres, depot, melanoma B16F1, pharmacokinetics. Introduction Parenteral depot systems have been the subject of intensive research eorts over the past two decades. These new drug delivery systems are injected or implanted into the muscle or subcutaneous tissue and release the incorporated drug in a controlled manner, allowing the adjustment of release rates over extended periods of time, ranging from several days up to 1 year (Danckwerts and Fassihi 1991, Bodmer et al. 1992). The release can be either continuous or pulsatile, depending on the structure of the device and the polymer characteristics. Continuous release pro®les are intended to generate infusion-like plasma level± time pro®les in the systemic circulation, without the necessity of hospitalization (GoÈ pferich et al. 1994). These release pro®les are useful for hormone replacement therapy. Pulsatile pro®les are of interest for vaccine delivery, where several injections are necessary to achieve protection. While most of the parenteral depot systems developed so far are designed to deliver drugs to the systemic j. microencapsulation, 2002, vol. 19, no. 4, 523±535 * To whom correspondence should be addressed. e-mail: shenoydin@yahoo.com Journal of Microencapsulation ISSN 0265±2048 print/ISSN 1464±5246 online # 2002 Taylor & Francis Ltd http://www.tandf.co.uk/journals DOI: 10.1080/02652040210141084