Enhanced nasal delivery of luteinizing hormone releasing hormone agonist buserelin by oleic acid solubilized and stabilized in hydroxypropyl-beta-cyclodextrin

Chemical & Pharmaceutical Bulletin
K AbeKaneto Uekama

Abstract

The potential use of three 2-hydroxypropyl ether derivatives of cyclodextrins (HP-alpha-, HP-beta- and HP-gamma-CyDs) as biocompatible solubilizers and stabilizers for oleic acid, a lipophilic absorption enhancer, was assessed in the nasal absorption of buserelin, an agonist of luteinizing hormone-releasing hormone, in rats. HP-CyDs increased the aqueous solubility of oleic acid and protected it against oxidation through the formation of inclusion complexes with the efficacy increasing in the order: HP-gamma-CyD < HP-alpha-CyD < HP-beta- CyD. The bend structure due to a cis-double bond halfway along the acyl chain of oleic acid provided a better fit into the cavity of HP-beta-CyD, in which the double bond appears to be buried, and hence becomes less susceptible to oxidation. The rate and extent of nasal bioavailability of buserelin were remarkably increased by coadministration of oleic acid and HP-beta-CyD, compared with the sole use of the enhancer. This enhancement was ascribable to the lowering of both the enzymatic and physical barriers of the nasal epithelium to the peptide, probably through the facilitated transmucosal penetration of oleic acid solubilized in HP-beta-CyD.

Citations

Jan 5, 2012·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kaneto Uekama
Jun 30, 2005·Journal of Pharmaceutical Sciences·Alexis Kays LeonardHenry R Costantino
Oct 22, 2014·Pharmaceutical Development and Technology·Mehdi RahimiAliasghar Behnamghader
Apr 19, 2011·International Journal of Pharmaceutics·Hussain Fatakdawala, Scott A Uhland
Aug 12, 2004·Chemical & Pharmaceutical Bulletin·Kaneto Uekama
Dec 4, 2004·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kaneto Uekama
Oct 9, 2003·Clinical Pharmacokinetics·Stanley S Davis, Lisbeth Illum
Mar 24, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Hsien-Tsung LuHsiu-O Ho
Dec 29, 2018·The Journal of Pharmacology and Experimental Therapeutics·Sunita YadavMansoor Amiji
Feb 1, 1997·Journal of Pharmaceutical Sciences·T Irie, K Uekama
Feb 19, 2002·Chemical Reviews·Kaneto UekamaTetsumi Irie
Jul 28, 2021·Advanced Drug Delivery Reviews·Matilde Durán-LobatoMaría José Alonso
May 4, 2007·International Journal of Pharmaceutics·Henry R CostantinoSteven C Quay

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.