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Natural Polymer-Based Nanogel for pH-Responsive Delivery of Sorafenib Tosylate in Hemangiosarcoma

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Abstract

Smart nanomedicinal treatment for cancer manifests a solubility challenge with inherent nanoscale size and nonspecific release with stimuli-responsive potential. This is the limelight in novel chemotherapy to pursue physiochemical differences between the tumor microenvironment (TME) and normal cells, which introduces active groups of nanocarriers responding to various stimuli, endowing them with concise responses to various tumor-related signals. The nanogels were successfully prepared by a modified solvent evaporation technique. Nine batches were formulated by changing the chitosan concentration (12, 14, 16 mg/ml) and sonication time (5, 10, 15 min). The formulations were optimized for particle size and zeta potential with high percent entrapment efficiency (%EE) through Central Composite Design software. The optimized batch F7 had a 182-nm size and high zeta potential (64.5 mV) with 98% EE. The drug release of F7 was higher at pH 6 (97.556%) than at pH 7.4 (45.113%). The pharmacokinetic study shows that the release follows the Hixon plot model (R2 = 0.9334) that shifts to zero order (R2 = 0.9149). The nanogel F7 was observed for stability and showed an absence of color change, phase separation, and opacity for 6 months. In the present study, the pH difference between cancer cells and normal cells is the key point of the smart nanogel. This study is promising but challenging depending on the in vivo study. The nanogel was successfully prepared and evaluated for pH-responsive release. As hemangiosarcoma commonly occurs in dogs, this formulation helps to limit the difficulties with administration.

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Acknowledgements

The authors would like to thank and acknowledge Dr. K.B. Burade, Principal of the Government College of Pharmacy for help and guidance throughout the research.

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Authors and Affiliations

  1. Department of Pharmaceutics, Government College of Pharmacy, Karad, Shivaji University, Kolhapur, Maharashtra, 415124, India

    Kiran K. Mali & Yogeshkumar N. Gavhane

  2. Department of Pharmaceutics, Krishna Foundation’s, Jaywant Institute of Pharmacy, Wathar, DBATU, Lonere, Karad, Maharashtra, 415139, India

    Kiran K. Mali

  3. Department of Pharmacy, Government College of Pharmacy, Karad, Shivaji University, Kolhapur, Maharashtra, 415124, India

    Rita D. Chakole

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  1. Kiran K. Mali
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Contributions

Ms. Kiran Mali performed the research under Mr. Yogeshkumar Gavhane and Dr. Rita Chakole guidance. Mr. Yogeshkumar Gavhane analyzed data related to formulation evaluation. Dr. Rita Chakole analyzed and interpreted data related to the chemical investigation of the drug and formulation.

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Correspondence to Kiran K. Mali.

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Mali, K.K., Gavhane, Y.N. & Chakole, R.D. Natural Polymer-Based Nanogel for pH-Responsive Delivery of Sorafenib Tosylate in Hemangiosarcoma. AAPS PharmSciTech 25, 83 (2024). https://doi.org/10.1208/s12249-024-02797-8

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