Protease-functionalized mucus penetrating microparticles: In-vivo evidence for their potential

Publication date: 30 October 2017 Source:International Journal of Pharmaceutics, Volume 532, Issue 1 Author(s): Arshad Mahmood, Flavia Laffleur, Gintare Leonaviciute, Andreas Bernkop-Schnürch The focus of the current study was to explore whether immobilization of proteases to microparticles could result in their enhanced penetration into mucus. The proteases papain (PAP) and bromelain (BROM) were covalently attached to a polyacrylate (PAA; Carbopol 971P) via amide bond formation based on carbodiimide reaction. Microparticles containing these conjugates were generated via ionic gelation with calcium chloride and were characterized regarding size, surface charge, enzymatic activity and fluorescein diacetate (FDA) loading efficiency. Furthermore, mucus penetration potential of these microparticles was evaluated in-vitro on freshly collected porcine intestinal mucus, on intact intestinal mucosa and in-vivo in Sprague–Dawley rats. Results showed mean diameter of microparticles ranging between 2–3μm and surface charge between −8 to −18mV. The addition of PAA-microparticles to porcine intestinal mucus led to a 1.39-fold increase in dynamic viscosity whereas a 3.10- and 2.12-fold decrease was observed in case of PAA-PAP and PAA-BROM microparticles, respectively. Mucus penetration studies showed a 4.27- and 2.21- fold higher permeation of FDA loaded PAA-PAP and PAA-BROM microparticles as compared to PAA microparticles, respectively. Extent of mucus diffusion determined...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research