Albendazole Nanocrystal-Based Dissolving Microneedles with Improved Pharmacokinetic Performance for Enhanced Treatment of Cystic Echinococcosis

Abstract

Cystic echinococcosis (CE) is a zoonosis caused by Echinococcus spp., affecting both humans and animals’ lives. Current treatment of CE by oral administration of albendazole (ABZ) is hampered by several limitations. The poor aqueous solubility and the rapid metabolism of ABZ in the liver are the main issues, leading to lack of efficacy of the treatment. In the present study, we developed a nanocrystalline (NC) formulation of ABZ to be delivered intradermally using dissolving microneedles (DMNs). The NC formulation was developed using milling in an ultrasmall-scale device. Following several screenings, Pluronic F127 was selected as a suitable stabilizer, producing NCs with around 400 nm in size with narrow particle distribution. The crystallinity of ABZ was maintained as observed by DSC and XRD analysis. The NC approach was able to improve the dissolution percentage of ABZ by approximately three-fold. Furthermore, the incorporation of NCs into DMNs using the combination of poly­(vinylpyrrolidone) and poly­(vinyl alcohol) formed sharp needles with sufficient mechanical strength and insertion properties. Dermatokinetic studies revealed that >25% of ABZ was localized in the dermis of excised neonatal porcine skin up to 48 h after DMN administration. In in vivo pharmacokinetic studies, the AUC and relative bioavailability values of ABZ delivered by NC-loaded DMNs were found to be significantly higher than those obtained after oral administration of coarse suspension of ABZ or ABZ-NCs, as well as DMNs delivering coarse ABZ as indicated by the relative bioavailability values of >100%. Therefore, the combination approach developed in this study could maintain the systemic circulation of ABZ, which could be possibly caused by avoiding the first-pass metabolism in the liver. This could be beneficial to improve the efficacy of ABZ in CE treatment.

Bioadhesive eutectogels supporting drug nanocrystals for long-acting delivery to mucosal tissues

“…The manufacture of NCs using laboratory media milling techniques has been previously described, allowing for the production of finely distributed particles in a scalable manner [ 35 ]. In this case, the particle size results agreed with those observed in previous reports using similar experimental setups [ 36 ]. During the milling process, there is an exponential increase in the surface area, which gives NCs some of their distinctive advantages, such as increased dissolution rate, saturation solubility and mucoadhesion [ 37 ].…”

Systemic delivery of tenofovir alafenamide using dissolving and implantable microneedle patches

“…The delivery efficiencies of dissolving, LV-PLGA and HV-PLGA were 39.84%, 10.69% and 59.25%, respectively. Whereas the low drug delivery efficiency of LV-PLGA MAPs was related to the poor mechanical properties of the formulation, dissolving and HV-PLGA MAPs showed similar drug delivery efficiencies to hose observed previously in the literature using similar formulations [ 41 , 45 , 46 ].

Fig.

…”

On a highway to the brain: A review on nose-to-brain drug delivery using nanoparticles

“…Microneedle patches are formed by a base plate from which microneedles (100 to 1500 µm in height) protrude from [147]. These patches are widely used for delivering hydrophilic and hydrophobic drug cargoes transdermally, both for topical and systemic effects [148][149][150]. The microneedles could physically help to circumvent the barriers of the intranasal route by piercing the outermost layers of the mucosa and producing drug accumulation in the brain [151].…”