Oral delivery of imatinib through galactosylated polymeric nanoparticles to explore the contribution of a saccharide ligand to absorption
Publication date: 10 September 2019Source: International Journal of Pharmaceutics, Volume 568Author(s): Yan Li, Baohui Yang, Xingwang ZhangAbstractImatinib (IMT) is a selective tyrosine kinase inhibitor clinically used for treating chronic myeloid leukemia and malignant gastrointestinal stromal tumors. However, oral administration of IMT is challenged by its high oral dose, low intestinal solubility and adverse reactions. This work aimed to investigate the effect of galactose ligand on polymeric nanoparticles-facilitated oral absorption of IMT. N-oleoyl-D-galactosamine was synthesized for fabricating biomimetic galactose-modified nanoparticles (GNPs) in an attempt to improve the oral bioavailability of IMT. IMT-loaded GNPs (IMT-GNPs) were prepared using a solvent diffusion technique and characterized by particle size, morphology, and entrapment efficiency (EE). The in vitro release and in vivo oral bioavailability of IMT-GNPs were comparatively studied with bulk IMT and IMT-loaded nanoparticles (IMT-NPs), respectively. The resultant IMT-GNPs were 122.0 nm around in particle size with a polydispersity index (PDI) of 0.201. IMT-GNPs possessed a high EE (93.06%) and exhibited a sustained effect on drug release. After oral administration, IMT-GNPs significantly enhanced the oral bioavailability of IMT, up to 152.3% relative to IMT suspensions, whereas IMT-NPs merely resulted in an increase to 115.2%. Cellular uptake and ex vivo intestinal transport imaging demonstrated that GNP...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research