Hydroxypropyl chitosan nail lacquer of ciclopirox-PLGA nanocapsules for augmented in vitro nail plate absorption and onychomycosis treatment

Abstract

Onychomycosis accounts for 90% of nail infections worldwide. Topical therapy provides localized effects with minimal adverse systemic actions, yet its effectiveness is limited by minimal drug permeation through the keratinized nail plate. Ciclopirox (CIX) is a FDA-approved broad-spectrum antimycotic agent. However, the complete cure with its nail lacquer (8% w/v) may continue for one year with a high cost. Therefore, poly lactide-co-glycolide (PLGA) nanocapsules (NCs) of CIX were prepared by nanoprecipitation and optimized through a 2 3 factorial design to be incorporated into hydroxypropyl chitosan (HPCH) based nail lacquer. Nail hydration, in vitro nail absorption, minimum inhibitory concentration (MIC), inhibition zones and ex vivo fungal growth on nail fragments were evaluated. The optimized NCs of CIX based on 100 mg PLGA 2 A and lipoid S75 showed a mean diameter of 174.77 ± 7.90 nm, entrapment efficiency (EE%) of 90.57 ± 0.98%, zeta potential (ZP) of −52.27 ± 0.40 mV and a prolonged drug release. Nail lacquer of the optimized NCs exhibited a higher stability than NCs dispersion. Compared to CIX solution (1% w/v), the respective decrease in MIC for NCs and their lacquer was four- and eight-fold. The lacquer superiority was confirmed by the enhancement in the nail hydration and absorption by 4 and 2.60 times, respectively, relative to CIX solution and the minimal ex vivo fungal growth. Therefore, HPCH nail lacquer of (1% w/v) CIX-PLGA-NCs can be represented as a potential topical delivery system for enhanced in vitro nail absorption and therapeutic efficacy against onychomycosis at a low dose.

Contemporary Techniques and Potential Transungual Drug Delivery Nanosystems for The Treatment of Onychomycosis

“…• It also strengthens the concept of fenestration as a pretreatment for the disease and provides a method for assessing novel agents or formulae [46] Poly lactide-co-glycolide (PLGA) nanocapsules Hydroxypropyl chitosan (HPCH) based nail lacquer • The drug-containing nanocapsules were prepared from PLGA and soybean phospholipid • A nail lacquer of the optimum formula displayed significant stability and double the decrease in MIC compared to the optimum formulation with higher absorption [47] Econazole nitrate Inhibition of ergosterol synthesis by interacting with 14-alpha-lanosterol demethylase, a cytochrome P-450 enzyme necessary for converting lanosterol to ergosterol Nail lacquer…”

“…For instance, nanocapsules are special nanosystems that are formulated with a lipophilic solid or liquid core encapsulated in a polymeric shell made of synthetic polymers like poly-lactic acid and poly-lactide-co-glycolide [39]. Ciclopirox olamine was formulated as core-coat polymeric nanocapsules, where poly lactide-co-glycolide was employed as a coat that protects the drug against rapid release from the oily core [47]. Another special nanosystem is the nanospheres, which were formulated using Eudragit RSPO or ethyl cellulose to accommodate terbinafine HCl.…”