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  • Title: Biodegradable nanoparticles from prosopisylated cellulose as a platform for enhanced oral bioavailability of poorly water-soluble drugs.
    Author: Kenechukwu FC, Dias ML, Ricci-Júnior E.
    Journal: Carbohydr Polym; 2021 Mar 15; 256():117492. PubMed ID: 33483021.
    Abstract:
    Bio-inspired nanotechnology-based strategies are potential platforms for enhanced dissolution and oral biovailability of poorly water-soluble drugs. In this study, a recently patented green biopolymer (Prosopis africana gum, PG) was compatibilized with microcrystalline cellulose (MCC), a conventional polysaccharide, via thermo-regulated coacervation to obtain PG-MCC (1:0, 1:1, 1:2, 2:1, and 0:1) rational blends and the nanoparticles developed with optimized (1:1) biocomposites (termed "prosopisylated cellulose") by combined homogenization-nanoprecipitation technique was engineered as a high circulating system for improved oral bioavailability of griseofulvin (GF), a model Biopharmaceutics Classification System (BCS) Class-II drug. The effects of biopolymer interaction on morphological and microstructural properties of drug-free biocomposites obtained were investigated by Fourier transform infra-red spectroscopy, scanning electron microscopy and x-ray diffractometry, while the physicochemical properties and in-vivo pharmacokinetics of GF-loaded nanoparticles were also ascertained. Optimized biocomposites revealed inter-molecular and intra-molecular hydrogen bonding between the hydroxyl group of MCC and polar components of PG, as well as reduction in crystallinity of MCC. Griseofulvin-loaded nanoparticles were stable, displayed particles with relatively smooth surfaces and average size of 26.18 ± 0.94 . nm, with zeta potential and polydispersity index of 32.1 ± 0.57 mV and 0.173 ± 0.06, respectively. Additionally, the nanoparticles showed good entrapment efficiency (86.51 ± 0.93 %), and marked improvement in griseofulvin dissolution when compared to free drug, with significantly (p < 0.05) higher GF release in basic than acidic PEG-reinforced simulated bio-microenvironments. Besides, x-ray diffractogram of GF-loaded nanoparticles showed amorphization with few characteristic peaks of GF while infra-red spectrum indicated broader principal peaks of GF and components compatibility. Furthermore, GF-loaded nanoparticles showed low plasma clearance with three-fold increase in systemic bioavailability of griseofulvin compared with free drug. These results showed that prosopisylated cellulose nanoparticles would be a facile approach to improve oral bioavailability of BCS class-II drugs and can be pursued as a new versatile drug delivery platform.
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