Characterization of folic acid-grafted poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles as carriers for sustained release of epirubicin.

• FA was grafted on PHB and PHBV to fabricate FA/PHB and FA/PHBV. • EPI was encapsulated in FA/PHB and FA/PHBV to produce drug-loaded nanoparticles. • Drug-loaded nanoparticles depicted pH-responsive sustained release of EPI. • Drug-loaded nanoparticles demonstrated time- and dose-dependent toxicity in MCF-7 cells. • Drug-loaded nanoparticles displayed enhanced cellular uptake and apoptosis. Polymeric nanoparticles coated with ligand molecules demonstrated great potential in targeted delivery of drug molecules to cancer cells. In this study, poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) were functionalized separately with folic acid (FA) to obtain FA/PHB and FA/PHBV, respectively. Subsequently, FA/PHB and FA/PHBV along with polyethylene glycol (PEG) were used for encapsulation of EPI to prepare the FA/PEG@EPI-PHB and FA/PEG@EPI-PHBV (drug-loaded) nanoparticles, respectively. Blank FA/PEG-PHB and FA/PEG-PHBV nanoparticles were also prepared. The FA/PEG@EPI-PHB nanoparticles (57±2.45 %) showed higher EPI loading as compared to FA/PEG@EPI-PHBV nanoparticles (43.16±1.35 %). A sustained release of EPI (65.70±5.10 %) was evident from FA/PEG@EPI-PHB nanoparticles at pH 5.5 for 28 h, thus following the Korsmeyer–Peppas mechanism. Enzymatic degradation of FA/PEG@EPI-PHB and FA/PEG@EPI-PHBV nanoparticles was carried out using lipases. The in-vitro cytotoxicity of FA/PEG@EPI-PHB and FA/PEG@EPI-PHBV nanoparticles was evaluated in the MCF-7 cell line. Blank nanoparticles did not inhibit the proliferation of the MCF-7 cell lines due to their non-toxicity and biocompatibility. The FA/PEG@EPI-PHB nanoparticles depicted 6.39-fold higher cytotoxicity in the MCF-7 cell line as compared to a similar quantity of free EPI. Additionally, cellular uptake and apoptotic behavior of FA/PEG@EPI-PHB nanoparticles were checked in the MCF-7 cell line. Thus, the FA/PEG-PHB targeted delivery system could be an efficient carrier for the sustained release of hydrophilic drug molecules to selectively kill a high proportion of tumor cells. [Display omitted] [ABSTRACT FROM AUTHOR]