A novel delivery system for enhancing bioavailability of S-adenosyl-l-methionine: Pectin nanoparticles-in-microparticles and their in vitro - in vivo evaluation

• Published in: Journal of drug delivery science and technology Vol. 61; p. 102096
• Main Authors: Dogan Ergin, Ahmet, Bayindir, Zerrin Sezgin, Ozcelikay, Arif Tanju, Yuksel, Nilufer
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-02-2021
• Subjects: Bioavailability enhancement; Colon targeting; Eudragit® L100; Fluidized bed coating; Nanoparticles-in-Microparticles; Pectin; S-Adenosyl-l-Methionine; S-Adenosyl-l-Methionine; Nanoparticles-in-Microparticles; Fluidized bed coating; Eudragit® L100; Pectin; Colon targeting; Bioavailability enhancement
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2020.102096

Nanoparticles-in-microparticles (NIMs) are novel drug delivery systems, which combine the benefits of nano-, and micro-sized drug carriers within one system to improve the bioavailability of drugs or provide site specific drug delivery. The goal of this work was to study the in vitro and in vivo characteristics of a new pectin nanoparticle based NIM formulation for colon targeted delivery of S-adenosyl-l-methionine (SAMe). The effects of different formulation parameters on physicochemical characteristics of pectin nanoparticles prepared by ionic-gelation method were estimated by a factorial design. The studied formulation variables were different amounts of drug, pectin and crosslinking agent. NIMs were prepared using fluidized bed technology by coating the optimum nanoparticle formulation (particle size 301.5 ± 20.3 nm, zeta potential: −16.3 ± 1.7 mV, entrapment efficiency: 74.80 ± 3.75%, product yield: 69.61%) on inert pellets via subcoating and pH- sensitive functional coating materials. NIMs were characterized by particle size, surface charge, morphology, entrapment efficiency, DSC, XRPD, in vitro drug release in the presence and absence of enzymes (pepsin and pectinase) in simulated gastric and colonic fluids. The in vitro drug release studies suggested retarded drug release, which was interpreted as an advantage for improving oral bioavailability of SAMe via colonic absorption. Comparative bioavailability of SAMe was determined after oral administration of pure SAMe solution, SAMe loaded pectin nanoparticles and NIMs to Wistar rats. Although inter-subject variability was observed, the relative bioavailability of SAMe (260%) increased via oral NIMs administration. This outcome should be supported with further bioavailability studies in larger groups. Overall, this study suggests that developed fluidized bed coating technique can be used to construct solid microparticular systems for colonic delivery of nanoparticles and overcome the difficulties in processing nanoparticles.
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