Diabetes Mellitus (DM) is a chronic endocrine disease categorized via boosting the blood glucose level and poor lipid, carbohydrate and protein metabolism. Crocetin exhibit the potent and oxidant and anti-inflammatory effect against various diseases. In this study, we developed surface-engineered poly(lactic-co-glycolic acid) (PLGA) nanocapsules encapsulating crocetin nano-formulation and scrutinized against streptozotocin induced DM in rats.

A modified solvent evaporation method was used for the formulation of PLGA-CT-NPs. For the optimization of nanoparticles particle size, surface charge, zeta potential and release kinetics was estimated. Single intraperitoneal administration of STZ (60 mg/kg) was used for the induction of DM in the Wistar rats and rats were received the oral administration of PLGA-CT-NPs for 28 days. The blood glucose level, insulin level, body weight was estimated at regular time intervals. The level of antioxidant, inflammatory cytokines, inflammatory and apoptosis parameters were estimated. The histopathology of pancreas and liver tissue evaluated. The real time PCR was performed to estimate the gene expression levels.

PLGA-CT-NPs were showed the particle size (140.1 ± 4.3 nm), polydispersity index (0.181± 0.03) and zeta potential (-18.4± 2.1 mV). The invitro release study showed the (82.4 ± 4.1%) release after 72 hr. PLGA-CT-NPs significantly (P<0.001) suppressed the glucose level and improved the level of insulin, along with body weight. PLGA-CT-NPs altered the level of antioxidant (MDA, SOD, CAT, GPx, GSH); cytokines (TNF-α, IL-1β, IL-6, IL-10); inflammatory parameters (COX-2, PGE2, NF-κB); apoptosis (Bax, Bcl-2, caspase-3), respectively. PLGA-CT-NPs altered the mRNA expression of AMPK, SIRT1, NF-κB, PI3K, Akt and TLR4.

Surface-engineered poly(lactic-co-glycolic acid) nanocapsules encapsulating crocetin may exert anti-diabetic potential via alteration of AMPK/SIRT1/NF-κB, PI3K/Akt and TLR4/COX-2 Signaling pathway.