Cellular mechanism of oral absorption of solidified polymer micelles

Eva Abramov, Flavia Cassiola, Ouri Schwob, Adi Karsh-Bluman, Mara Shapero, James Ellis, Dema Luyindula, Irit Adini, Robert J. D'Amato, Ofra Benny*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Oral delivery of poorly soluble and permeable drugs represents a significant challenge in drug development. The oral delivery of drugs remains to be the ultimate route of any drugs. However, in many cases, drugs are not absorbed well in the gastrointestinal tract, or they lose their activity. Polymer micelles were recognized as an effective carrier system for drug encapsulation, and are now studied as a vehicle for oral delivery of insoluble compounds. We characterized the properties of monomethoxy polyethylene glycol-poly lactic acid (mPEG-PLA) micelles, and visualized their internalization in mouse small intestine. Using Caco-2 cells as a cellular model, we studied the kinetics of particle uptake, their transport, and the molecular mechanism of their intestinal absorption. Moreover, by inhibiting specific endocytosis pathways, pharmacologically and genetically, we found that mPEG-PLA nanoparticle endocytosis is mediated by clathrin in an energy-dependent manner, and that the low-density lipoprotein receptor is involved. From the Clinical Editor: Many current drugs used are non-water soluble and indeed, the ability to deliver these drugs via the gastrointestinal tract remains the holy grail for many researchers. The authors in this paper developed monomethoxy polyethylene glycol-poly lactic acid (mPEG-PLA) micelles as a drug nanocarrier, and studied the mechanism of uptake across intestinal cells. The findings should improve our current understanding and point to the development of more nanocarriers.

Original languageAmerican English
Pages (from-to)1993-2002
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume11
Issue number8
DOIs
StatePublished - 1 Nov 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

  • Caco-2
  • Nanomedicine
  • Oral delivery
  • Polymer micelles
  • mPEG-PLA

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