Poly(DL-lactide-co-glycolide) microporous microsphere-based depot formulation of a peptide-like antineoplastic agent

Abstract

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.

Keywords::

• Bleomycin
• Plga
• Microspheres
• Depot
• Melanoma B16f1
• Pharmacokinetics