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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

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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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Acknowledgments

The authors are thankful to Director, ISF College of Pharmacy, Moga, for providing financial assistance from the institutional reserve fund to one of the authors RKK and necessary infrastructure and facilities to carry out this research work. We are also thankful to Fresenius Kabi Oncology Ltd, Baddi (india) and Psyco Remedies Limited, Ludhiana, Punjab for providing Doxorubicin and Metformin HCL, respectively, as gift samples to carry out this investigations.

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Authors and Affiliations

  1. Associate Professor, Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, 142001, India

    Rajveer Kaur Kang, Neeraj Mishr & Vineet Kumar Rai

  2. Amity Institute of Pharmacy, Amity University Madhya Pradesh, Gwalior, Madhya Pradesh, India

    Neeraj Mishr

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  1. Rajveer Kaur Kang
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  2. Neeraj Mishr
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Correspondence to Vineet Kumar Rai.

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Kang, R.K., Mishr, N. & Rai, V.K. 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. AAPS PharmSciTech 21, 48 (2020). https://doi.org/10.1208/s12249-019-1589-3

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