Abstract
Smart nanomaterials with stimuli-responsive behavior are considered as promising platform for various drug delivery applications. Regarding their specific conditions, such as acidic pH, drug carriers to treatment of tumor microenvironment need some criteria to enhance drug delivery efficiency. In this study, for the first time, pH-sensitive BSA-stabilized graphene (BSG)/chitosan nanocomposites were synthesized through electrostatic interactions between the positively charged chitosan nanoparticles and negatively charged BSG and used for Doxorubicin (DOX) encapsulation as a general anticancer drug. Physicochemical characterization of the nanocomposites with different concentrations of BSG (0.5, 2, and 5wt%) showed effective decoration of chitosan nanoparticles on BSG. Comparing DOX release behavior from the nanocomposites and free BSG-chitosan nanoparticles were evaluated at two pHs of 7.4 and 4.5 in 28 days. It was shown that the presence of BSG significantly reduced the burst release observed in chitosan nanoparticles. The nanocomposite of 2wt% BSG was selected as the optimal nanocomposite with a release of 84% in 28 days and with the most uniform release in 24 h. Furthermore, the fitting of release data with four models including zero-order, first-order, Higuchi, and Korsmeyer-Peppas indicated that the addition of BSG changed the release mechanism of the drug, enabling uniform release for the optimal nanocomposite in first 24 h, compared to that for pure chitosan nanoparticles. This behavior was proved using metabolic activity assay of the SKBR-3 breast cancer cell spheroids exposed to DOX release supernatant at different time intervals. It was also demonstrated that DOX released from the nanocomposite had a significant effect on the suppression of cancer cell proliferation at acidic pH.
Highlights
Smart nanomaterials with stimuli-responsive behavior are considered as promising platform for various drug delivery applications
In the IR spectra of the DOX-encapsulated chitosan nanoparticles, the appearance of 1716 cm−1 and 1510 cm−1 peaks are related to the vibration of the carbonyl ketone group and C–C vibration of the benzene ring in the doxorubicin structure and confirms the presence of the drug encapsulated inside the chitosan nanoparticles s tructure[48,49]
The bovine serum albumin (BSA)-stabilized graphene (BSG)/chitosan nanocomposites were prepared in three wt% of BSG (0.5, 2, and 5)
Summary
Smart nanomaterials with stimuli-responsive behavior are considered as promising platform for various drug delivery applications. The fitting of release data with four models including zeroorder, first-order, Higuchi, and Korsmeyer-Peppas indicated that the addition of BSG changed the release mechanism of the drug, enabling uniform release for the optimal nanocomposite in first 24 h, compared to that for pure chitosan nanoparticles. This behavior was proved using metabolic activity assay of the SKBR-3 breast cancer cell spheroids exposed to DOX release supernatant at different time intervals. The sustained release within 24 h leads to the release of 100% indole-3-acetic a cid[42]
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