Polymeric nanoparticles for the delivery of Sonoran desert propolis: Synthesis, characterization and antiproliferative activity on cancer cells

Abstract

Sonoran propolis (SP) exerts remarkable biological activities attributed to its polyphenolic composition, mostly described as poplar-type flavonoids. It is known that polyphenols present low bioavailability derived of their molecular weight, glycosylation level, metabolic conversion, as well as interaction with the intestinal microbiota, affording limitations for possible in vivo applications. The aim of this work was to synthesize Poly-(lactide-co-glycolide) acid (PLGA) nanoparticles for encapsulation of SP, as a matrix to increase solubility of their polyphenolic compounds and improve delivery, for the evaluation of its antiproliferative activity on cancer cells. The Sonoran propolis-loaded PLGA nanoparticles (SP-PLGA NPs) were synthesized (by nanoprecipitation), and their physicochemical parameters were determined (size, morphology, zeta potential, stability, and drug release). Additionally, the antiproliferative activity of SP-PLGA nanoparticles was evaluated in vitro against murine (M12.C3.F6) and human (HeLa) cancer cell lines, including a non-cancer human cell line (ARPE-19) as control. SP-PLGA NPs presented a mean size of 152.6 ± 7.1 nm with an average negative charge of - 21.2 ± 0.7 mV. The encapsulation yield of SP into PLGA system was approximately 68.2 ± 6.0% with an in vitro release of 45% of propolis content at 48 h. SP-PLGA NPs presented antiproliferative activity against both cancer cell lines tested, with lower IC₅₀ values in M12.C3.F6 and HeLa cell lines (7.8 ± 0.4 and 3.8 ± 0.4 μg/mL, respectively) compared to SP (24.0 ± 4.3 and 7.4 ± 0.4 μg/mL, respectively). In contrast, the IC₅₀ of SP-PLGA NPs and SP against ARPE-19 was higher than 50 µg/mL. Cancer cells treated with SP and SP-PLGA NPs presented morphological features characteristic of apoptosis (cellular shrinkage and membrane blebs), as well as elongated cells, effect previously reported for SP, meanwhile, no morphological changes were observed with ARPE-19 cells. The obtained delivery system demonstrates appropriate encapsulation characteristics and antiproliferative activity to be used in the field of nanomedicine, therefore SP could be potentially used in antitumoral in vivo assays upon its encapsulation into PLGA nanoparticles.

Keywords: Drug delivery; Propolis PLGA nanoparticles; Propolis encapsulation; Sonoran Desert propolis.