Guar Gum Micro-particles for Targeted Co-delivery of Doxorubicin and Metformin HCL for Improved Specificity and Efficacy Against Colon Cancer: In Vitro and In Vivo Studies
Abstract
Doxorubicin and Metformin HCL is a known chemotherapeutic combination that wipes out tumors and prevents their recurrence. However, limited site specificity confines its application. Here we report Doxorubicin and Metformin HCL–loaded guar gum micro-particles prepared by emulsification cum-solidification method. Developed micro-particles were characterized as spherical shape particles with smooth surface and micro size diameter. Encapsulation of drugs in combination was confirmed by their characteristic functional groups (FT-IR), change in phase transition temperature (DSC) and X-ray diffraction pattern (XRD). Particles were observed to be stable at 25 and 5°C. The in vitro Doxorubicin and Metformin HCL release study in simulated gastric (SGF), intestinal (SIF) and colonic fluid (SCF) confirms restricted release in SGF (9.3 and 9.6%, respectively, in 2 h) and SIF (10.8 and 14.7%, respectively, in the next 3 h) and highest release in SCF (about 68 and 73.3%, respectively) in colon. Developed micro-particles showed 78% recovery in tumor volume and considerable improvement in histological changes. X-ray images confirmed good target ability of micro-particles to colon. In conclusion, the specially designed, stable micro-particles are able to target drug combination to colon and improve efficacy by ensuring maximum drug release in colon as compared with Doxorubicin and Metformin HCL combination.
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