Formulation and optimization of Naringin polymeric nanoparticles: Optimization to in vivo evaluation

The oral route is the most common route for the delivery of therapeutic agents but has limitations to poorly soluble therapeutics like intrasubject variability and low bioavailability. The application of nanoparticles can be used to enhance the bioavailability and therapeutic activity of drugs. The objective of the study was to develop naringin (NN) loaded nanoparticles (NP) using chitosan (C) and sodium alginate (S) as polymers. NN-NP were prepared by ionotropic gelation method and optimized by Box–Behnken design (BBD) using chitosan (A), sodium alginate (B), and sonication time (C) as independent factors. The prepared NN-NP was optimized on the basis of particle size (Y₁) and entrapment efficiency (Y₂). The optimized naringin nanoparticles (NN-NPo) were further evaluated for X-ray diffraction, in-vitro release, ex-vivo permeation, and in-vivo pharmacokinetic and pharmacodynamic study. NN-NPo has a particle size of 163.4 ± 3.1 nm, entrapment efficiency of 93.2 ± 3.8%, PDI of 0.24, and positive zeta potential (38.3 mV). X-ray diffractogram showed that NN completely encapsulated the polymer matrix. In-vitro release study results exhibited a sustained drug release profile (91.60 ± 3.4% in 24 h) than pure NN (96.10 ± 3.6% in 24 h). The permeation study results showed a significant enhancement in flux (58.43 ± 3.9 μg/cm².h) than pure NN dispersion (19.38 ± 2.6 μg/cm².h). It also exhibited a significantly (P < 0.05) higher apparent permeability coefficient with a 3.1 enhancement ratio than pure NN. The pharmacokinetic study results revealed a significantly (P < 0.05) high absorption profile (AUC_0-24) and antidiabetic activity than pure NN-dispersion. The biochemical profile also remarkably improved in altered biochemical parameters. The findings concluded that polymeric NN-NP would be an alternative delivery for the enhancement of therapeutic efficacy.