Context: Physiologic barriers of the eye, short precorneal drug residence time and poor corneal penetration are the few reasons for reduced ocular bioavailability.
Objective: This study was aimed to develop novel polymer-surfactant nanoparticles of hydrophilic drug doxycycline hydrochloride (DXY) to improve precorneal residence time and drug penetration.
Materials and methods: Nanoparticles were formulated using emulsion cross-linking method and the formulation was optimized using factorial design. The prepared formulation was characterized for particle size, ζ potential, encapsulation efficiency, in vitro drug release and ex vivo drug diffusion studies. The antibacterial activity studies were also carried out against Escherichia coli and Staphylococcus aureus using the cup-plate method. In vivo eye irritation study was carried out by a modified Draize test in rabbits.
Results and discussion: The particle size was found to be in the range of 331-850 nm. About 45-80% of the drug was found to be encapsulated in the nanoparticles. In vitro release demonstrated sustained release profile. Lower flux values in case of nanoparticles as compared to DXY pure drug solution in ex vivo diffusion studies confirmed the sustained release. The nanoparticles were found to be significantly effective (p < 0.001) than DXY aqueous solution due to sustained release of doxycycline from nanoparticles in both the E. coli and S. aureus strains. The formulation was found to be stable over entire stability period.
Conclusion: The developed formulation is safe and suitable for sustained ocular drug delivery.
Keywords: Emulsion cross-linking method; factorial design; gellan gum; polymer–surfactant nanoparticles; sustained release.