Bile Salt–Fatty Acid Mixed Micelles as Nasal Absorption Promoters of Peptides. I. Effects of Ionic Strength, Adjuvant Composition, and Lipid Structure on the Nasal Absorption of [D-Arg2]Kyotorphin
- 1 January 1990
- journal article
- Published by Springer Science and Business Media LLC in Pharmaceutical Research
- Vol. 7 (2), 127-133
- https://doi.org/10.1023/a:1015868516602
Abstract
Bile salts and synthetic surfactants have been used to promote nasal absorption of peptide drugs. Although a marked increase in nasal absorption has been achieved, this may not be adequate and the possibility of adjuvant-induced membrane toxicity exists. The present study employs a rat in situ nasal perfusion technique and mixed micelles between sodium glycocholate (NaGC) and various lipids as potential nasal absorption enhancers of a stable model dipeptide, [D-Arg2]kyotorphin. NaGC alone enhanced the nasal absorption of the dipeptide in a concentration-dependent manner. When linoleic acid was added to form mixed micelles with NaGC, the absorption was further enhanced (P < 0.01). The effect of mixed micelles was synergistic and much greater than with single adjuvants. Increasing ionic strength was found to increase the adjuvant activity of both NaGC and NaGC–lipid mixed micelles. Structure of the lipid component of the mixed micelles also affected the adjuvant potency. Oleic acid, a cis-unsaturated fatty acid, was more effective than elaidic acid, the trans-isomer, whereas cis-linoleic acid and trans-linolelaidic acid were equally effective (α = 0.05). Mixed micelles of mono-glycerides such as monoolein and monolinolein were also more effective than NaGC alone (α = 0.05). Micellar solubilization of these polar lipids by NaGC appears to be important for nasal absorption enhancement to occur. Reversal of the membrane permeability was also observed within approximately 20–40 min after removal of the adjuvants from the rat nasal cavity. These observations are similar to the effects of mixed micelles on the rectal mucosa and may involve the same mechanism.Keywords
This publication has 22 references indexed in Scilit:
- Transport of tyrosine and phenylalanine across the rat nasal mucosaLife Sciences, 1988
- Effect of Bile Salts on Nasal Permeability In VitroJournal of Pharmaceutical Sciences, 1987
- The promotion of drug rectal absorption by water absorptionJournal of Pharmacy and Pharmacology, 1985
- Involvement of Active Sodium Transport in the Rectal Absorption of Gentamicin Sulfate in the Presence and Absence of Absorption-PromotingAdjuvantsJournal of Pharmaceutical Sciences, 1983
- Solvent drag effect in drug intestinal absorption. II. Studies on drug absorption clearance and water influx.Journal of Pharmacobio-Dynamics, 1982
- Intestinal transport of bile acids.1981
- Nasal absorption of propranolol in humansJournal of Pharmaceutical Sciences, 1980
- Micelle Formation and Testosterone Solubilization by Sodium GlycocholateJournal of Pharmaceutical Sciences, 1972
- Perfusion of the Hamster Jejunum with Conjugated and Unconjugated Bile Acids: Inhibition of Water Absorption and Effects on MorphologyGastroenterology, 1972
- Bile Salt-Induced Permeability Changes in the Isolated Rat IntestineExperimental Biology and Medicine, 1969