Optimization of the Process Variables for the Development of Enteric Coated Colon Targeted Nanoparticles of Quercetin and Evaluation of its Pharmacokinetics, Biodistribution and Targeting Potential

The current study aimed to design and characterize a colon targeted drug delivery system for quercetin dihydrate (QDH). The developed nanoparticles were assessed using various in vitro and in vivo criteria.

Oil-in-oil solvent evaporation process was used for coating of Eudragit S 100 (ES 100) on QDH loaded chitosan nanoparticles (QLCN) to achieve colon targeted QLCN (ES-QLCN). To optimize formulation of ES-QLCN, Box- Behnken Design (BBD) was used. Optimized ES-QLCN was subjected for long term and accelerated stability study as per ICH guidelines. Furthermore, the optimized ES-QLCN was subjected to in vivo pharmacokinetic and biodistribution study. Moreover, correlation at levels B and C for optimized ES-QLCN formulation with available in vitro dissolution and in vivo absorption data has been established.

Optimized formulation of ES 100 coated QLCN (ES-QLCN) showed an average Particle size (PS) 234.6 ± 2.48 nm, Polydispersity index (PDI) 0.318 ± 0.01, % Entrapment efficiency (% EE) 73.7 ± 2.06 and Cumulative % drug release (% CDR) at 2 h and % CDR at 12 h were found to be 3.82 ± 0.59% and 64.83 ± 1.13% respectively. The results of stability study indicated no any significant changes in evaluation criteria. The result of in vivo pharmacokinetic study indicated that the relative bioavailability of ES-QLCN enhanced by 8.47 fold as compared to that of pure QDH. The developed nanocarriers accumulated well in the colon, according to an in vivo biodistribution study. The findings of Level B and Level C IVIVC revealed a significant correlation with a correlation coefficient of 0.9787 and 0.9581 respectively.

The ES 100 coating on QLCN restricts the release of QDH in the upper gastrointestinal tract, exhibiting efficient colon drug targeting, according to an in vitro release study and an in vivo pharmacokinetic and biodistribution study of nanoparticle formulations.