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Extended Release of Metronidazole Drug Using Chitosan/Graphene Oxide Bionanocomposite Beads as the Drug Carrier.

ABSTRACT: This study depicts the facile approach for the synthesis of chitosan/graphene oxide bionanocomposite (Chi/GO) beads via the gelation process. This is the first-ever study in which these Chi/GO beads have been utilized as a drug carrier for the oral drug delivery of metronidazole (MTD) drug, and investigations were made regarding the release pattern of the MTD drug using these Chi/GO beads as a drug carrier for a prolonged period of 84 h. The MTD is loaded on the surface as well as the cavity of the Chi/GO beads to result in MTD-Chi/GO bionanocomposite beads. The MTD drug loading was found to be 683 mg/g. Furthermore, the in vitro release patterns of pure drug and the drug encapsulated with Chi/GO beads are explored in simulated gastric as well as simulated intestinal fluids with phosphate-buffered saline (PBS) of pH 1.2 and 7.4, respectively. As-synthesized bionanocomposite beads have shown excellent stability and capacity for extended release of the MTD drug as compared to the pure drug in terms of bioavailability in both media. The cumulative release data are fitted with the Korsmeyer-Peppas kinetics and first-order reaction kinetics at pH 1.2 and 7.4. The synthesized bionanocomposite beads have good potential to minimize the multiple-dose frequency with the sustained drug release property and can reduce the side effects due to the drug.

SUBMITTER: Kumar G

PROVIDER: S-EPMC8359167 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Intratumoral (IT) injection of chemotherapeutics into needle-accessible solid tumors can directly localize the anticancer drug in the tumor site, thus increasing its local bioavailability and reducing its undesirable effects compared to systemic administration. In this study, graphene oxide (GO)-based chitosan/β-glycerophosphate (CS/GP) thermosensitive injectable composite hydrogels (CH) were prepared and optimized for the localized controlled delivery of doxorubicin (DOX). A quality-by-design (QbD) approach was used to study the individual and combined effects of several formulation variables to produce optimal DOX-loaded GO/CS/GP CH with predetermined characteristics, including gelation time, injectability, porosity, and swelling capacity. The surface morphology of the optimal formulation (DOX/opt CH), chemical interaction between its ingredients and in vitro release of DOX in comparison to GO-free CS/GP CH were investigated. Cell viability and cellular uptake after treatment with DOX/opt CH were studied on MCF 7, MDB-MB-231 and FaDu cell lines. The statistical analysis of the measured responses revealed significant effects of the concentration of GO, the concentration of CS, and the CS:GP ratio on the physicochemical characteristics of the prepared GO/CS/GP CH. The optimization process showed that DOX-loaded GO/CS/GP CH prepared using 0.1% GO and 1.7% CS at a CS: GO ratio of 3:1 (v/v) had the highest desirability value. DOX/opt CH showed a porous microstructure and chemical compatibility between its ingredients. The incorporation of GO resulted in an increase in the ability of the CH matrices to control DOX release in vitro. Finally, cellular characterization showed a time-dependent increase in cytotoxicity and cellular uptake of DOX after treatment with DOX/opt CH. The proposed DOX/opt CH might be considered a promising injectable platform to control the release and increase the local bioavailability of chemotherapeutics in the treatment of solid tumors.

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Extended Release of Metronidazole Drug Using Chitosan/Graphene Oxide Bionanocomposite Beads as the Drug Carrier.

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