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Synthesis of hydrogels for combinatorial delivery of 5-fluorouracil and leucovorin calcium in colon cancer: optimization, in vitro characterization and its toxicological evaluation

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Abstract

Chemical cross-linking of monomers methacrylic acid (MAA) and itaconic acid (IA) through ethylene glycol dimethacrylate (EGDMA) was carried out for synthesizing robust hydrogel system for oral administration and tuned for targeted release of 5-fluorouracil (5-FU) and leucovorin calcium (LV) at colonic site. Aqueous-based free radical polymerization method was optimized first, and then a series of batches were prepared. Various in vitro tests were performed to probe the characteristics of synthesized hydrogels such as the presence of functional groups, surface morphology, crystalline/amorphous properties and thermal stability which confirms the cross-linking and stability of hydrogels. Swelling, drug loading and drug release evaluations were carried out at two different pH levels of 1.2 and pH 7.4. pH responsiveness was observed in synthesized hydrogels. Co-polymeric hydrogels exhibited higher swelling and release at higher pH 7.4 as compared to lower pH 1.2. Moreover, an increased trend in swelling and drug release was observed for formulations with higher content of IA. Co-polymeric hydrogels were biocompatible and non-toxic to biological system as investigated by acute oral toxicity study on rabbits.

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Authors and Affiliations

  1. Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Railway Road, Khawaja Fareed Campus, Bahawalpur, Punjab, 63100, Pakistan

    Orva Abdullah, Muhammad Usman Minhas, Mahmood Ahmad, Sarfaraz Ahmad & Aousaf Ahmad

  2. College of Pharmacy, University of Sargodha, University Road, Sargodha City, Punjab, Pakistan

    Muhammad Usman Minhas

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  1. Orva Abdullah
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  2. Muhammad Usman Minhas
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  3. Mahmood Ahmad
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  5. Aousaf Ahmad
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Correspondence to Muhammad Usman Minhas.

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Abdullah, O., Usman Minhas, M., Ahmad, M. et al. Synthesis of hydrogels for combinatorial delivery of 5-fluorouracil and leucovorin calcium in colon cancer: optimization, in vitro characterization and its toxicological evaluation. Polym. Bull. 76, 3017–3037 (2019). https://doi.org/10.1007/s00289-018-2509-5

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  • DOI: https://doi.org/10.1007/s00289-018-2509-5

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