Hydrophobically modified Chitosan-Pluronic nanocarriers for controlled release of Nimodipine and HC-067047 drugs in ischemic tissues

Amin, Keristina and Imre-Deák, Ágota and Farkas, Eszter and Rose, Christine R. and Bari, Ferenc and Janovák, László (2025) Hydrophobically modified Chitosan-Pluronic nanocarriers for controlled release of Nimodipine and HC-067047 drugs in ischemic tissues. MATERIALS TODAY CHEMISTRY, 46. No.-102743. ISSN 2468-5194

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Abstract

This research demonstrates that hydrophobically modified chitosan (Chit) with adequate pH sensitivity can deliver drugs to ischemic brain tissues (pH 6.5–6.0). In this study, Chit was modified using hydrophobic hexyl and dodecyl aldehydes in reductive amination reactions. DSC and TG analyses showed that increasing the aldehydic side chain length reduced Chit's water content from 78.5 % to 47.1 %. Consequently, the cut-off pH for nanoparticle (NP) formation was reduced from 7.45 (initial Chit) to 6.74 (hexyl aldehyde modified Chit, C6-chit) and 2.49 (dodecyl aldehyde modified Chit, C12-chit). To target drug release in ischemic regions, the C6-chit polymer was selected for NP development. Different amounts of Pluronic F127 (PF) were incorporated within these NPs to achieve controlled and sustained drug release. The NPs successfully encapsulated two hydrophobic drugs, Nimodipine (NIMO) and HC-067047 (HC). Notably, this study is the first to achieve HC encapsulation within any polymeric particles. The encapsulated drugs exhibited reduced crystallinity compared to bare forms, enhancing both water solubility and stability in aqueous medium. The pH-responsive drug release profiles highlighted the potential of releasing drugs in ischemic tissues rather than normal ones. Additionally, increasing the PF content resulted in prolonged drug release at pH 6, thereby extending the therapeutic effect.

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