Formulation of nanoparticles loaded in situ gel for treatment of dry eye disease: In vitro, ex vivo and in vivo evidences

Abstract Dry eye disorder is the most common ophthalmic complication which has already affected millions of people worldwide. Due to protective response of eye, conventional drops get rapidly eliminated from eye site. Moreover; current treatment of dry eye syndrome demands frequent administration of formulation. Henceforth; there is need to develop novel ocular drug delivery system to meet the need. By considering the involvement of Peroxisome proliferator-activated receptor-γ in dry eye, we prepared Pioglitazone loaded Poly (D, L-lactide-co-glycolide) nanoparticles which were then suspended in temperature sensitive in situ gel prepared by combination of Poloxamer 407 and HPMC K4M those also contribute in treatment as lubricant. Nanoparticle system and in situ formulation was optimised by 32 factorial design. Optimized nanoparticle system was evaluated for particle size, PDI, % entrapment efficiency, XRD, DSC and then suspended in polymeric in situ gel. In situ gel was characterized by viscosity, %drug release, gelation temperature, gelling strength, sterility test, preservative efficacy test. Ocular irritation potential was confirmed by histology study on goat eye cornea. Formulation retained the normal structure of cornea and found non-irritant. Effectiveness of optimised formulation in comparison to existing marketed formulation was estimated by Schirmer’s test on mice. Prepared formulation showed induced tear production and further stabilised tear film for long period in comparison to marketed formulation. It can be concluded that prepared formulation can be consider as alternative for existing treatment.