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Insight into novel β-cyclodextrin-grafted-poly (N-vinylcaprolactam) nanogel structures as advanced carriers for 5-fluorouracil: Equilibrium behavior and pharmacokinetic modeling

Abstract Novel β-cyclodextrin-grafted-N-vinylcaprolactam nanogel structures (β-CD-g-PNVCL NG) were synthesized with different ratios by free radical graft copolymerization in aqueous media. The synthetic nanogel structures were characterized by different techniques including… Click to show full abstract

Abstract Novel β-cyclodextrin-grafted-N-vinylcaprolactam nanogel structures (β-CD-g-PNVCL NG) were synthesized with different ratios by free radical graft copolymerization in aqueous media. The synthetic nanogel structures were characterized by different techniques including XRD, FT-IR, SEM, HRTEM, TGA, and DSC as an advanced carrier for 5-fluorouracil drug (5-FU) with stunning loading properties and controlled release behavior. The results revealed that the preparation of the gel at 1 (β-CD):5 (PNVCL) ratio resulted in the best loading capacity (qmax 659.7 mg/g) and the most controlled releasing profile. The loading behavior can be described excellently by Langmuir model followed by the Freundlich model reflecting homogenous and monolayer loading of the adsorbed 5-FU molecules. Additionally, the adsorption energy (11.62 KJ/mol) from the Dubinin–Radushkevich model revealed chemical uptake for the drug molecules. The releasing profile is of controlled features and continued for 30 h especially in the intestinal fluid (pH 7.4) without complete releasing of the loaded 5-FU drug molecules and the maximum released percentage is 68 %. The pharmacokinetics studies for the commonly inspected theoretical models reflected the best fitting of the results with the Higuchi model as well as the Korsmeyer-Peppas model. The obtained values of the diffusion exponent related to non-Fickian transport behavior and associated with diffusion and erosion as releasing mechanisms with dominance for the diffusion process during the initial stages. β-CD-g-PNVCL NG is of low cytotoxicity on the normal cells and after loading it by 5-FU drug it showed higher toxicity effect than the free 5-FU drug molecules on HCT-116 cells which confirmed the role of β-CD-g-PNVCL NG carrier in enhancing the performance of 5-FU drug as anticancer chemotherapy.

Keywords: vinylcaprolactam nanogel; cyclodextrin grafted; novel cyclodextrin; drug; nanogel structures; behavior

Journal Title: Colloids and Surfaces A: Physicochemical and Engineering Aspects
Year Published: 2020

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