In this study, latanoprost molecules was linked to mucoadhesive nanocarrier, chitosan (CS) and hyaluronic acid (HA) that can control the drug release and prolong residence time in ocular tissues that will lead to better ocular availability. The development of the CS-tripolyphosphate (TPP) nanoparticles was prepared by ionic gelation method. Scanning electron pictographs showed nanoparticles that are spherical and are embedded in free chitosan elongated structures. The particle-size, zeta-potential (ZP) and polydispersity-index (PDI) were determined by dynamic light scattering. High performance liquid was used for the quantitation of latanoprost. The optimum CS: TPP ratio had the lowest particle size of 198 nm, with PDI of 0.274, ZP of +27.7mV and an entrapment efficiency (EE) of 62%. It was further coated with HA, where the optimum HA: CS ratio had the lowest particle size of 314 nm, with a PDI of 0.424, ZP of +29.87 mV and an EE of 72%. In the in vitro drug release study, the optimum HA coated CS-latanoprost link nanoparticle formulation has 0% drug release in 30 minutes, 29% in 2 hours and 87% in 8 hours as compared with the conventional latanoprost solution that released 28% of the drug in 30 minutes, and 100% in 2 hours. Release mechanism of the drug from the polymeric nanoparticles matrix led to a zero order kinetic with a correlation coefficient of 0.9848. Drug release could also be expressed by Higuchi’s equation as the plot showed linearity at 0.9492, where the value of diffusion exponent obtained from the Korsemeyer-Peppas model is 1.13. Addition of mucin to the positively charged nanoparticles reduced the ZP to an average of -4.30 mV. The draize test on albino rabbits showed the polymeric nanoparticle were safe for ophthalmic use. The results of this study could serve as a basis that mucoadhesive HA coated CS-latanoprost-link nanoparticles could provide a prolonged ocular delivery system of latanoprost for better glaucoma treatment.
Keywords: latanoprost, chitosan, hyaluronic acid, nanoparticles, prolonged drug delivery,