Development of polymeric nanoparticle gel prepared with the combination of ionic pre-gelation and polyelectrolyte complexation as a novel drug delivery of timolol maleate.

Objective: The purpose of this study was to overcome the undesired systemic absorption of skin topical administration of timolol maleate (TM) by developing the TM nanoparticle gel.
Methods: TM-loaded nanoparticle (TMNP) was prepared by ionic pre-gelation of pectin (PCN) and calcium ions (CI) followed with polyelectrolyte complex using chitosan (CHI). TMNP was characterized by measuring the particle size, polydispersity index, zeta potential, encapsulation efficiency (EE), and the interaction between formula constituents. TM-loaded nanoparticle gel (TMNG) was prepared by using hydroxypropyl methylcellulose (HPMC) and was characterized by measuring the spreadability, pH, viscosity, and drug content. The drug release kinetics were analyzed using DDSolver add-in program.
Results: TMNP possessed particle size of 175.2 ± 19.7 nm, polydispersity index of 0.528 ± 0.113, zeta potential of -10.86 ± 0.87 mV, and EE of 27.45 ± 2.34%. The electrostatic interactions between PCN, CI, and CHI that formed the nanoparticles were confirmed by the result of vibrational spectroscopy analysis. TMNG possessed spreadability of 60.80 ± 1.38 cm ² , pH of 5.154 ± 0.004, viscosity of 269.07 ± 5.83 cP, and drug content of 107.38 ± 1.77%. TM showed a sustained release manner within 24 h by following Korsmeyer-Peppas kinetical model with non-Fickian release mechanism.
Conclusion: The prepared nanoparticle gel can be an effective controlled release system of TM that administered topically on the skin surface.