Reduced toxicity and enhanced antitumor efficacy of plumbagin using poly (lactic-co-glycolic) biodegradable injectable implant

Objective: To prepare poly (lactic-co-glycolic) acid (PLGA) injectable gel implant for the delivery of plumbagin (PLB) to reduce the toxicity and enhance the antitumour efficacy. Method: PLGA was dissolved in triacetin and PLB was dissolved in this. A gel matrix was formed immediately on contact with aqueous fluid. In vitro release studies were carried out in phosphate buffered saline pH 7.4. Acute toxicity studies were performed in normal BALB/c mice and antitumour efficacy in BALB/c mice bearing Sarcoma-180 tumour. LD₅₀ and volume doubling time (VDT) values for plain PLB and gel implant injection was found after subcutaneous injection. Results: In vitro release of PLB was observed for a week. It was dependent on the concentration of PLGA used. The LD₅₀ for plain PLB and gel implant was found to be 8.60 mg/kg and 9.33 mg/kg. VDT for plain PLB and gel implant was found to be 6.5±0.9 days and 11.5±0.5 days respectively. Conclusion: The toxicity of PLB was reduced in mice after subcutaneous injection of the gel containing PLB compared to plain PLB. The VDT was significantly higher for the gel compared to plain PLB. Thus the gel implant could be an effective drug delivery system for reducing toxicity and enhancing the therapeutic efficacy of PLB.