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Chitosan-Graft-Poly (N-Isopropylacrylamide)Co-Polymer as a Carrier for Targeted Delivery and Enhanced Catalytic Activity of Capecitabine

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Abstract

The efficient biodistribution and controlled release of medications or genes at specific site are made possible by the use of stimuli-responsive or intelligent polymers. Pathologically challenged tissue has fundamental qualities that are very different from those of typical, healthy cells. These characteristics have been useful in creating endostimuli-responsive nanocarriers for the efficient delivery of drug cargoes. The site-specific release of medications delivered by nanocarriers can take advantage of the tumour microenvironment's increased temperature and acidic pH. Capecitabine, is enzymatically catalysed to 5-FU, the active compound by sequential enzymatic steps with the last step catalyzed by the tumor-associated angiogenic factor thymidine phosphorylase which is more abundantly expressed in many types of human tumours than in healthy tissues catalyses. Thus, the site specific delivery of capacitabine to tumor microenvironment enhance its catalytic activity and increase the selectivity of 5-FU for tumor cells and decrease plasma levels of 5-FU. The goal of this research was to synthesize the co-polymer chitosan-g- poly (N-isopropylacrylamide) (CS-g-PNIPAm) and evaluate it as a dual responsive carrier for targeted Capecitabine delivery. For this, the co-polymer was synthesized, its responsiveness was optimized to tumour microenvironment conditions of pH and temperature. The Capecitabine was subsequently encapsulated in the synthesised co-polymer, and the physicochemical properties of the produced nanoparticles were assessed. When comparing the physiological pH and temperature to acidic pH (6.8) and higher temperature (39 °C), the in vitro stimuli driven drug release investigation found that the percent drug release was greater at acidic pH (6.8) and higher temperature (39 °C). MTT assay as well asfluorescence microscopic study demonstrated significantly increased drug release in tumor microenvironment while showed minimal effect at physiological conditions. In conclusion, the synthesizedco-polymer appear to be an an efficient dual pH and temperature responsive carrier for targeted delivery of anti-cancer drug Capecitabine to enhance its catalytic activity. Higher levels of FU are thus produced within tumours with minimal exposure of healthy tissue to FU.

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Authors and Affiliations

  1. Department of Pharmaceutics, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research, Belagavi, Karnataka, 590010, India

    Archana S. Patil

  2. Viatris Inc., Hyderabad, Telangana, 500049, India

    Nitin P. Ambhore

  3. Department of Pharmaceutical chemistry, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research, Belagavi, Karnataka, 590010, India

    Shailendra S. Suryawanshi & Parixit J. Bhandurge

  4. Department of Pharmacology, Aditya Bangalore Institute of Pharmacy Education and Research, Kogilu Main Road, Yelahanka, Banglore, India

    Deeparani K. Urolagin

  5. Department of Pharmacology, TVM College of Pharmacy, Bellary, Karnataka, 583104, India

    Sivaiah Kummara

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Patil, A.S., Ambhore, N.P., Suryawanshi, S.S. et al. Chitosan-Graft-Poly (N-Isopropylacrylamide)Co-Polymer as a Carrier for Targeted Delivery and Enhanced Catalytic Activity of Capecitabine. Top Catal 65, 2005–2020 (2022). https://doi.org/10.1007/s11244-022-01705-3

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