Development of Forskolin and rutin-loaded polymeric nanoparticles for enhancement of topical ocular delivery: Optimization, in-vitro, ex-vivo, and toxicity evaluation

The present study was to develop forskolin (F) and rutin (R)-loaded chitosan (CS)-coated poly lactic-co-glycolic acid (PLGA) nanoparticles (NP) for the improvement of ocular delivery. The FRCS-PLGA-NP was prepared by emulsification and evaporation and optimized by design expert software (box-bhekhen design). The concentration of CH, PLGA, and polyvinyl alcohol (PVA) was used as an independent variable, and particle size (nm) and polydispersity index (PDI) were taken as dependent variables. Optimized FRCS-PLGA-NP (F13) showed 136.64 ± 5.74 of particle size, 0.23 ± 0.04 PDI, 76.65 ± 1.21% EE for forskolin, and 72 ± 0.75% EE for rutin. FTIR study showed there is no interaction between the drug and the excipients. X-ray diffractogram exhibited the forskolin and rutin were encapsulated in a polymer matrix. FRCSPLGA-NP (F13) showed the sustained release of forskolin (70.87 ± 3.45% in 24 h) and rutin (65.14 ± 3.04% in 24 h) respectively. FRCS-PLGA-NP-opt (F13) showed significantly high permeation i.e., 55.24 ± 2.43% for forskolin and 47.28 ± 3.42% for rutin respectively. The FRCS-PLGA-NP-opt (F13) exhibited significant bio-adhesion and no toxicity confirmed by corneal hydration, histology of cornea, and HET-CAM test. The finding revealed that CS-PLGA-NP is alternative delivery of forskolin (F) and rutin (R) for the improvement of therapeutic performance.