Co-encapsulation of combinatorial flavonoids in biodegradable polymeric nanoparticles for improved anti-osteoporotic activity in ovariectomized rats

Abstract

In our study a novel nanocombination of flavonoids was synthesized for anti-osteoporotic therapeutics. We chose 2 flavonoids, quercetin and curcumin to be encapsulated in polylactic-co-glycolic acid (PLGA) for anti-osteoporotic activity in induced ovariectomized rats. The synthesized flavonoids co-encapsulated PLGA nanoparticles were analysedfor morphological changes with electron micrography and its zeta potential along with PDI was determined. The encapsulation and loading efficiency studies were performed along with in vitro release studies. Cytotoxicity of the synthesized nanoparticles was evaluated with primary bone cells. The administration of the flavonoid co-encapsulated nanoparticles was done intragastrically after which the physical parameters of the femur, compression test of lumbar vertebra were studied. Weight of ash, % of ash and ash calcium of femoral bone were calculated along with biochemical characterization of serum. The histopathological examination of femur was done too. The synthesized flavonoids co-encapsulated PLGA nanoparticles were small enough (110–135 nm) and exhibited homogeneous distribution. The high encapsulation and loading efficiencies demonstrated a favourable nanocombination. The cytotoxicity results exhibited the cytocompatibility of the nanoparticles. From the in-vivo studies, it was seen that the flavonoids co-encapsulated PLGA nanoparticles inhibited trabecular bone loss and significantly improved bone mineral density and bone microarchitecture. The flavonoids loaded PLGA nanoparticles augmented the protective effect to prevent bone loss after ovariectomy. This study may be furthered for novel therapeutic management of osteoporosis. • Quercetin and curcumin encapsulated in PLGA nanoparticles. • Encapsulation and loading efficiency studies with in-vitro release. • in-vivo studies show inhibited trabecular bone loss and improved bone density. • The protective effect on bone loss got augmented after ovariectomy.