Delivery of peptides to the blood and brain after oral uptake of quaternary ammonium palmitoyl glycol chitosan nanoparticles

Molecular Pharmaceutics
A LalatsaI F Uchegbu

Abstract

The clinical development of therapeutic peptides has been restricted to peptides for non-CNS diseases and parenteral dosage forms due to the poor permeation of peptides across the gastrointestinal mucosa and the blood-brain barrier. Quaternary ammonium palmitoyl glycol chitosan (GCPQ) nanoparticles facilitate the brain delivery of orally administered peptides such as leucine(5)-enkephalin, and here we examine the mechanism of GCPQ facilitated oral peptide absorption and brain delivery. By analyzing the oral biodistribution of radiolabeled GCPQ nanoparticles, the oral biodistribution of the model peptide leucine(5)-enkephalin and coherent anti-Stokes Raman scattering microscopy tissue images after an oral dose of deuterated GCPQ nanoparticles, we have established a number of facts. Although 85-90% of orally administered GCPQ nanoparticles are not absorbed from the gastrointestinal tract, a peak level of 2-3% of the oral GCPQ dose is detected in the blood 30 min after dosing, and these GCPQ particles appear to transport the peptides to the blood. Additionally, although peptide loaded nanoparticles from low (6 kDa) and high (50 kDa) molecular weight GCPQ are taken up by enterocytes, polymer particles with a polymer molecular weigh...Continue Reading

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Citations

Aug 7, 2013·Nanomedicine·Mark E Keating, Hugh J Byrne
Apr 6, 2013·Therapeutic Delivery·Dolores Remedios Serrano Lopez, Aikaterini Lalatsa
Mar 8, 2014·Molecular Pharmaceutics·Aikaterini LalatsaIjeoma F Uchegbu
Jan 8, 2013·ACS Nano·Mariarosa MazzaIjeoma F Uchegbu
Jul 5, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anastasia ZubarevaЕlena Svirshchevskaya
Nov 24, 2012·Journal of Pharmaceutical Sciences·Ijeoma F Uchegbu, Adeline Siew
Dec 3, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·A LalatsaI F Uchegbu
Jan 3, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lindsey CrawfordDavid Putnam
Mar 6, 2012·Journal of Biophotonics·Natalie Laura GarrettJulian Moger
Oct 12, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Vivek K PawarManish K Chourasia
Apr 29, 2014·Nanomedicine : Nanotechnology, Biology, and Medicine·Libo DuYang Liu
Jan 7, 2015·Molecular Pharmaceutics·Dolores R SerranoIjeoma F Uchegbu
Nov 19, 2013·Pharmaceutical Patent Analyst·Louise Rosenmayr-Templeton
Apr 15, 2014·Journal of Peptide Science : an Official Publication of the European Peptide Society·Ashkan DehsorkhiIan W Hamley
Mar 6, 2019·Nanomaterials·Sally Vanden-HehirAlison N Hulme
Dec 29, 2020·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Nicole KuhlmannKlaus Brandenburg
Jun 2, 2020·Advanced Drug Delivery Reviews·D J BraydenR J Mrsny
Jan 26, 2021·Chemical Society Reviews·Juan PellicoRafael T M de Rosales
Feb 12, 2021·International Journal of Pharmaceutics·Moutaz Y BadrIjeoma F Uchegbu
Apr 22, 2021·Journal of Immunology Research·Adriana Bezerra-SouzaLuiz Felipe D Passero
May 22, 2021·Nanoscale Horizons : the Home for Rapid Reports of Exceptional Significance in Nanoscience and Nanotechnolgy·Tony JinAudrey Moores
May 16, 2018·Molecular Pharmaceutics·Lindsay SmithAikaterini Lalatsa

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