Oral delivery of folate-targeted resveratrol-loaded nanoparticles for inflammatory bowel disease therapy in rats.
Life Sci. 2020 Oct 6 ;262:118555. Epub 2020 Oct 6. PMID: 33035579
AIMS: In the current study, resveratrol-loaded PLGA nanoparticles targeted with folate were developed in order to protect resveratrol from fast degradation, modify its pharmacokinetics and increase its intestinal permeation. Then, the therapeutic efficacy of the prepared system was evaluated in suppression of colon inflammation on TNBS-induced colitis model.
MAIN METHODS: In this regard, resveratrol was encapsulated in PLGA and FA-conjugated PLGA in order to prepare non-targeted (PLGA-RSV) and targeted (PLGA-FA-RSV) platforms, respectively.
KEY FINDINGS: Obtained results demonstrated that the prepared formulations encapsulated the resveratrol with high encapsulation efficiency of 90.7% ± 5.1% for PLGA-RSV and 59.1% ± 3.3% for PLGA-FA-RSV. In vitro release experiment showed that the prepared formulations were capable of retaining good amount of resveratrol under the simulated gastric condition (HCl 0.1 N, pH 1.2), while significant amount of resveratrol was released undersimulated intestinal condition (PBS, pH 7.4). The trans-well permeability rates through Caco-2 monolayer during 180 min, was determined to be 4.5%, 61% and 99% for resveratrol, PLGA-RSV and PLGA-FA-RSV respectively. The pathological analysis of the rat intestinal sections (hematoxylin&eosin staining) at 7th day post-TNBS colonic inflammation induction illustrated that the oral administrations of FA-PLGA-RSV and PLGA-RSV were able to significantly inhibit the inflammation and reduce neutrophil and lymphocytes accumulation. It is worth noting that the folate-targeted system demonstrated highest efficacy in suppressing colon inflammation.
SIGNIFICANCE: It could be concluded that the encapsulation of resveratrol into biodegradable folate-targeted PLGA nanoparticles could introduce a potent platform in suppressing colonic inflammation thus offering a great capability for clinical translation.