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Understanding mechanical characteristics of pH-responsive PEG 4000-based polymeric network for colorectal carcinoma: its acute oral toxicity study

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Abstract

The major objective of this study is to fabricate a very promising system by loading anticancer agent in it which could be given to the cancer patients by oral administration and additionally that will liberate drugs in large intestine (affected/cancerous area). Minimum or no exposure of chemotherapeutic agents to gastric/small intestine will significantly eliminate the problem of adverse drug reactions. Cancer patients are facing severe problem of side/adverse effects due to intravenous colorectal carcinoma chemotherapy. So, an oral drug delivery system is designed to substitute the intravenous drug therapy. This study reports the synthesis of hybrid polymeric polyethylene glycol hydrogels (PEGA 4000) based on acrylic acid (AA), ammonium peroxodisulfate and ethylene glycol dimethacrylate (EGDMA) by solution polymerization method. PEGA 4000 hydrogels were used for colon targeting of hydrophilic anti-carcinoma drug (oxaliplatin). Development of new structure was confirmed by Fourier transform infrared spectroscopy. Surface morphology of developed hydrogel slabs was examined by scanning electron microscopy. Thermal gravimetric analysis of hydrogels revealed that there was an increase in thermal stability of PEGA 4000 hydrogels. Swelling study was performed in acidic and basic pH medium provided important information on drug release characteristics of hydrogels. The release of oxaliplatin (OXP) was significantly retarded at pH 1.2, while rapid release was observed at pH 7.4. The release rate of OXP increased with increasing concentration of PEG 4000 and AA. However, extent of drug release was significantly reduced on increasing concentration of EGDMA. Mechanism of release has been evaluated by applying various mathematical kinetic models. The tensile mechanical strength and elongation at break were also observed on different formulations based on various ratios of reaction contents. The consequents of our study suggest that fabricated PEGA 4000 hydrogels could serve as suitable target release delivery system and toxicity study endorsed biocompatibility of hydrogels to biological system.

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Acknowledgements

Authors are grateful to the Faculty of Pharmacy and Alternative Medicine, the Islamia University of Bahawalpur, Pakistan, which rendered us all conveniences, chemicals and equipment to carry out this study.

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Authors and Affiliations

  1. Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, Punjab, 63100, Pakistan

    Kashif Barkat, Mahmood Ahmad & Ikrima Khalid

  2. Faculty of Pharmacy, University of Lahore, Lahore, Punjab, 54000, Pakistan

    Kashif Barkat & Asif Mahmood

  3. College of Pharmacy, University of Sargodha, Sargodha, Punjab, Pakistan

    Muhammad Usman Minhas

  4. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, GC University, Faisalabad, Punjab, Pakistan

    Ikrima Khalid

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  1. Kashif Barkat
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  2. Mahmood Ahmad
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Correspondence to Mahmood Ahmad.

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Barkat, K., Ahmad, M., Minhas, M.U. et al. Understanding mechanical characteristics of pH-responsive PEG 4000-based polymeric network for colorectal carcinoma: its acute oral toxicity study. Polym. Bull. 78, 5075–5101 (2021). https://doi.org/10.1007/s00289-020-03356-4

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  • DOI: https://doi.org/10.1007/s00289-020-03356-4

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