Chitosan/PLA nanoparticles as a novel carrier for the delivery of anthraquinone: Synthesis, characterization and in vitro cytotoxicity evaluation

Designing novel materials for biomedical applications generally require the use of biodegradable materials. This study aims to engineer a biodegradable [chitosan (CS) and poly (lactic acid) (PLA)] as AQ carrier with nanometer dimensions and to evaluate the anticancer potency of the prepared CS/PLA–AQ NPs in human carcinoma (HepG2) cells. CS–PLA complex, which are well dispersed and stable in aqueous solution, was prepared by the precipitation of lactic acid in chitosan solution by dropping method and characterized by SEM, TEM, DLS and FTIR. The results thus displayed that the prepared nanoparticles carried a positive charge and showed the size in the range from 100 to 200 nm. The in vitro (AQ) release study showed that these nanoparticles provided a continuous release of the entrapped AQ for 10 days, and the release behavior was influenced by the pH value of the medium thereby making feasible to develop CS–PLA for enhanced and sustained release of AQ. MTT assay revealed higher cytotoxic efficacy of CS/PLA–AQ NPs than Free AQ in HepG2 cells. Further, the mitochondrial membrane damage indicated by loss of mitochondrial membrane potential and necrotic cell death could be attributed to the increased reactive oxygen species production. Our results also suggest that upon CS/PLA–AQ NPs exposure the cell viability decreased due to apoptosis, as demonstrated by the formation of apoptotic bodies, sub-G1 hypodiploid cells, and DNA fragmentation. Henceforth, CS/PLA–AQ NPs demonstrated a strong antitumor activity in vitro by reducing cell viability, inducing cell necrosis, decreasing the negative surface charge and mitochondrial membrane potential, and fragmenting DNA.

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► The current approach is mainly based on the entrapment of an antioxidant agent into the polymeric matrix to be protected and transported by the bloodstream.
► In this study, a simple method of synthesis and characterization of a novel cationic PLA coated with chitosan encapsulated formulation of anthraquinone that can improve the solubility of anthraquinone and prevents RES uptake.
► The size of CS/PLA–AQ NPs, AQ loading and release experiments indicate that this system seems to be a very promising vehicle for the administration of chemopreventing agent and promote cytotoxicity in HepG2 cells which suggest the concept of nanochemoprevention possesses strong advantage and motivation for conducting additional detailed in vivo studies in appropriate animal models with relevance to human disease.