Dual-purpose Injectable Doxorubicin Conjugated Alginate Gel Containing Polycaprolactone Microparticles for Anti-cancer and Anti-inflammatory Therapy

Background: In situ gel formulations have been widely reported as a carrier for sustained release delivery systems due to certain advantages such as targeted drug delivery, minimal invasiveness and potent therapeutic activity. Objective: Herein, in situ gel system for sustained release of doxorubicin and ibuprofen for anti-cancer and anti-inflammatory activity is reported. Method: Doxorubicin-conjugated alginate (dox-alg) gel was prepared using EDC-NHS chemistry and loaded with ibuprofen encapsulated polycaprolactone (PCL) microparticles (dox-alg composite). PCL microparticles were prepared by a solvent evaporation method (size 50 - 100μm). The gel was characterized using SEM, FTIR, XRD and TGA analysis. Results: Dox-alg composite gel showed good syringeability and gel formation properties. Burst release was observed for both drugs within 24 h followed by sustained release till day 21. Doxorubicin released from composite showed considerable cytotoxic effect. Cell uptake was confirmed by confocal microscopy using MDA-MB-231 cells. Anti-inflammatory activity of ibuprofen released from composite gel was compared with the free drug. An injection of dox-alg composite gel in the tissue would fill the void created after tumor removal surgery, prevent the resuscitation of remnant cancerous cells and reduce inflammation. Conclusion: Thus, the dox-alg composite gel could be a potential agent for the dual anti-cancer and anti-inflammatory therapy.