Characterization of folic acid-grafted poly(3-hydroxybutyrate) and poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles as carriers for sustained release of epirubicin
JOURNAL OF MOLECULAR STRUCTURE(2024)
摘要
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-3hydroxyvalerate) (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@EPIPHB 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.
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关键词
Cancer,Epirubicin,Folic acid,PHA Nanoparticles,pH -sensitive,Targeted drug delivery
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