title: Positively charged polymeric nanoparticle reservoirs of terbinafine hydrochloride: preclinical implications for controlled drug delivery in the aqueous humor of rabbits.
abstract: Frequent instillation of terbinafine hydrochloride (T HCl) eye drops (0.25%, w/v) is necessary to maintain effective aqueous humor concentrations for treatment of fungal keratitis. The current approach aimed at developing potential positively charged controlled-release polymeric nanoparticles (NPs) of T HCl. The estimation of the drug pharmacokinetics in the aqueous humor following ocular instillation of the best-achieved NPs in rabbits was another goal. Eighteen drug-loaded (0.50%, w/v) formulae were fabricated by the nanopreciptation method using Eudragit® RS100 and chitosan (0.25%, 0.5%, and 1%, w/v). Soybean lecithin (1%, w/v) and Pluronic® F68 (0.5%, 1%, and 1.5%, w/v) were incorporated in the alcoholic and aqueous phases, respectively. The NPs were evaluated for particle size, zeta potential, entrapment efficiency percentage (EE%), morphological examination, drug release in simulated tear fluid (pH 7.4), Fourier-transform IR (FT-IR), X-ray diffraction (XRD), physical stability (2 months, 4°C and 25°C), and drug pharmacokinetics in the rabbit aqueous humor relative to an oily drug solution. Spherical, discrete NPs were successfully developed with mean particle size and zeta potential ranging from 73.29 to 320.15 nm and +20.51 to +40.32 mV, respectively. Higher EE% were achieved with Eudragit® RS100-based NPs. The duration of drug release was extended to more than 8 h. FT-IR and XRD revealed compatibility between inactive formulation ingredients and T HCl and permanence of the latter's crystallinity, respectively. The NPs were physically stable, for at least 2 months, when refrigerated. F5-NP suspension significantly (P<0.05) increased drug mean residence time and improved its ocular bioavailability; 1.657-fold.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini, 11562, Cairo, Egypt.
authors.forename: Saadia Ahmed
authors.initials: SA
authors.lastname: Tayel
authors.forename: Mohamed Ahmed
authors.initials: MA
authors.lastname: El-Nabarawi
authors.forename: Mina Ibrahim
authors.initials: MI
authors.lastname: Tadros
authors.forename: Wessam Hamdy
authors.initials: WH
authors.lastname: Abd-Elsalam
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D060433:Administration, Ophthalmic; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D054709:Lecithins / Q000737:chemistry; D008297:Male; D053758:Nanoparticles; D036103:Nanotechnology; D009281:Naphthalenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D009883:Ophthalmic Solutions; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D000077291:Terbinafine
chemical_list: D000180:Acrylic Resins; D000935:Antifungal Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D054709:Lecithins; D009281:Naphthalenes; D009883:Ophthalmic Solutions; D020442:Poloxamer; C050528:Eudragit RS; D048271:Chitosan; D000077291:Terbinafine