Indian Propolis Loaded Folic Acid Conjugated PLGA Nanoparticles: Formulation Development, Characterization, In Vitro and In Vivo Anticancer Study

Abstract

Propolis, a natural bee hive product is well proven for its anticancer potential due its various polyphenols and flavonoids constituents. Anticancer efficacy of propolis is limited due to its poor water solubility and bioavailability. The present study is investigated for design and development of ethanolic extract of Indian propolis (EEIP) loaded folic acid conjugated Poly (D,L-lactide-co-glycolide) nanoparticles (denoted as ELFPN) were investigated to achieve improved solubility, sustained drug release and to study synergized anticancer efficacy. Formulation development, characterization and optimization were carried out by design of experiment approach. . In vitro and in vivo cytotoxicity study was carried out for optimized formulation. Developed ELFPN showed the particle size and encapsulation efficiency 178 ± 5 - 205 ± 5 nm and 73.16 ± 1.89 - 76.37 ± 1.89 respectively. Optimized formulation showed sustained drug release over a period of 48 h with no sign of blood toxicity. Moreover, concentration of the drug needed for growth inhibition of 50 % of cells in a designed time period (GI50) was decreased by 43.34 %, for ELFPN as compared to EEIP in human breast cancer MCF-7 cells indicating targeting with synergistic effect of ELFPN. An improved anticancer effect was reflected in in-vivo Daltons Ascites Lymphoma model by reducing tumor cells count. The developed ELFPN showed improved in vitro cytotoxic effect, in-vivo anti-cancer activity with desirable characteristics for nanoparticle formulation thus can be useful for biomedical applications.