Apically targeted oral micelles exhibit highly efficient intestinal uptake and oral absorption
Authors Wang JL, Wang LF, Li Y, Wang XH, Tu PF
Received 13 August 2018
Accepted for publication 9 October 2018
Published 26 November 2018 Volume 2018:13 Pages 7997—8012
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Linlin Sun
Jinling Wang, Lifang Wang, Ying Li, Xiaohui Wang, Pengfei Tu
School of Chinese Materia Medica, Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
Introduction: Polymeric micelles (PMs) hold promise for improving solubility and oral absorption of poorly soluble drugs. Unfortunately, the oral absorption of PMs is also limited by intestinal epithelium. To improve the oral delivery efficiency of micelles, transporter-mediated micelles could enhance the transport efficiency across the epithelial barrier, and they have attracted more attention.
Methods: Peptide transporter 1 (PepT1)-mediated micelles (Val-PMs/Phe-PMs) were designed by grafting valine (or phenylalanine) onto the surface of curcumin (Cur)-loaded-D-α-tocopheryl polyethylene glycol 1000 succinate micelles (TP-PMs). The oral absorption mechanism and oral bioavailability were further investigated in vitro and in vivo.
Results: The cellular study showed that Val-PMs/Phe-PMs had a high PepT1 affinity, resulting in a higher drug uptake and transcellular transport than TP-PMs. In rats, Val-PMs/Phe-PMs exhibited higher intestinal accumulation in the apical side of the intestinal epithelium than TP-PMs, promoting drug diffusion across epithelial barrier. The oral bioavailability of Cur was significantly improved by Val-PMs/Phe-PMs, which was about 10.50- and 3.40-fold greater than that of Cur-Sol and TP-PMs, respectively.
Conclusion: PepT-1-mediated micelles, using PepT1 as a target on intestinal epithelium, have unique functions with intestine and prove promising for oral delivery of poorly water-soluble drugs.
Keywords: PepT1, micelles, epithelial barrier, curcumin, oral delivery
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