Positively Charged Polymeric Nanoparticle Reservoirs of Terbinafine Hydrochloride: Preclinical Implications for Controlled Drug Delivery in the Aqueous Humor of Rabbits

Abstract

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.

Pathogenesis of microbial keratitis

“…Corneal collagen cross-linking (CXL) is a relatively new technique currently been investigated in conjunction with photo-activated riboflavin (PAR) in refractory keratitis cases [102,137]. Investigations into the use of nanoparticle technology with terbinafine and silver have also shown promising results [189,214]. In addition, topical aqueous garlic extracts have been tested on rabbit keratitis models infected with A. flavus [76].…”

Duodenum-triggered delivery of pravastatin sodium: II. Design, appraisal and pharmacokinetic assessments of enteric surface-decorated nanocubosomal dispersions

“…Briefly, the samples were mixed with potassium bromide (1:10, w/w) and pressed to form a disc. Since the potassium bromide has no absorption in the fundamental FT-IR spectrum region, only the spectrum of the investigated sample is obtained (Tayel et al, 2013).…”

“…Consequently, the cubosomal dispersions having z-average values4150 nm were excluded from further studies (Tayel et al, 2015).…”

“…Yet, most of the reported methods suffer from many limitations including the lengthy production steps, the use of organic solvents, the need of special sophisticated equipment and/or the limited scaling up possibilities. In a previous work (Tayel et al, 2015), the authors developed a challenging surface-coating, duodenum-triggered, approach for PVS-loaded spanlastics using Eudragit Õ L100-55. Based on the adopted freeze drying technique, no organic solvent was needed and the possibility of scaling-up could be achieved in a single-step.…”

Fungal Keratitis: Update for 2014

“…Investigations into the use of nanoparticle technology with terbinafine and silver have shown promise [66,67]. There has been an attempt to develop an antimicrobial contact lens incorporating melimine into the lens substance [68].…”