Liquid crystal nanoparticle containing pirfenidone for the treatment of corneal lesions: development, characterization and in vivo evaluation

Due to the low bioavailability of drugs given via eye drops (only 1 to 5% of the drug is absorbed), release systems that allow for increased permeation and drug retention time are increasingly being used. In this context, liquid crystals using monolein are systems that control the release of drugs and promote bioadhesion action. Some recent studies have shown that pirfenidone (PFD), a drug used to treat idiopathic pulmonary fibrosis, has favorable results in the healing process of the cornea. However, PFD exhibits short half-life after topical application and in this context a liquid crystal nanoparticle system containing pirfenifdone (PFD-LCNPs) was developed. PFD-LCNPs were prepared using monolein / oleic acid / poloxamer 107 / water by a top-down method. The nanoparticles were characterized by transmission electron microscopy, atomic force microscopy, low angle X-ray diffraction (SAXS) and polarized light microscopy. The PFD-LCNPs showed particle size and zeta potential of 247.3 ± 0.59 nm and -33.60 ± 1.06 mV (when stored at 4 ° C), respectively. When stored at 25 ° C, they had particle size and zeta potential of 257.5 ± 5.57 nm and -46.00 ± 2.45 mV, respectively. The pH of the formulation was 6.9 ± 0.01 and the encapsulation rate was 35.9 ± 2.09%. The formulation when stored at 4 ° C showed stability for 30 days, according to the variation of backscatting profile, pH, particle size and zeta potential evaluated 30 days after preparation. In vitro release profiles indicated that PFD-LCNPs maintained the release for more than 6 h. The study of ocular irritation using the Hen's egg chorioallantoic membrane test (HET-CAM) concluded that the components of NPCLs-PFD are non-irritating and well tolerated for ocular administration. The corneal reepithelialization time after chemical burning was significantly reduced in rabbits treated with NPCLs-PFD (1mg/mL) when compared to controls. In addition, the anti-inflammatory action of pirfenidone was observed by the reduction of myeloperoxidase activity (MPO) and inflammatory cells in the histology of animals treated with PFD-LCNPs. This suggests that the PFD-LCNPs constitute a promising system for the treatment of corneal lesions. (author)