A pH-sensitive nanocarrier based on BSA-stabilized graphene-chitosan nanocomposite for sustained and prolonged release of anticancer agents

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.

Artificial engineering of the protein corona at bio-nano interfaces for improved cancer-targeted nanotherapy

“…A critical challenge in developing NP-based drug delivery systems is to alter the kinetics of drug release in a controllable manner [198,199]. The release profile data for different nanocarriers should be reevaluated by incorporating the impact of the PC on the rate of drug release to make it applicable for in vivo applications.…”

Recent Development of Nano-Carbon Material in Pharmaceutical Application: A Review

“…In the release of DOX, high concentrations of Chi and DOX will decrease the surface area of bare graphene and becomes conducive to DOX release based on the pH setting of the Chi protonation state. Next year, Farahani et al [ 211 ] modified Graphene-Chi with Bovine Serum Albumin (BSA) which helps stabilize graphene-Chi and bind DOX. BSA(Graphene) nanocomposites in three different presentations, 0.5%, 2%, and 5% by weight of BSA, were dispersed in distilled water at pH 10 and then magnetically stirred with Chi-DOX.…”

Advances in Biologically Applicable Graphene-Based 2D Nanomaterials

“…pH-sensitive BSA-stabilized GR/chitosan (CS) nanocomposites, encapsulating DOX, were tested for drug release at pH 7.4 and pH 4.5, for one month. The presence of bovine serum albumin (BSA) in nanocomposite pronouncedly reduced the burst release observed in CS NPs nanocomposite and nanocomposite containing 2 wt% of GR released 84% of DOX in 28 days, with uniform release in the first 24 h; the released drug from the nanocomposite greatly inhibited the proliferation of SK-BR-3 breast cancer cells at acidic pH [ 95 ]. It should also be noted that antibacterial GR-based hydroxyapatite/CS coating with gentamicin exhibited considerable antibacterial effect against Staphylococcus aureus , causing a reduction in viable cells with >3 logarithmic units, while in Escherichia coli it showed a bacteriostatic effect, reducing the number of viable cells <3 logarithmic units.…”