Dual-purpose Injectable Doxorubicin Conjugated Alginate Gel Containing Polycaprolactone Microparticles for Anti-Cancer and Anti-Inflammatory Therapy

Abstract

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. Herein, in situ gel system for sustained release of doxorubicin and ibuprofen for anti-cancer and anti-inflammatory activity is reported. 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. 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. Thus, the dox-alg composite gel could be a potential agent for the dual anti-cancer and anti-inflammatory therapy

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