In Vitro and In Vivo Evaluation of a Water-in-Oil Microemulsion System for Enhanced Peptide Intestinal Delivery

Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 1

Abstract

Peptide and protein drugs have become the new generation of therapeutics, yet most of them are only available as injections, and reports on oral local intestinal delivery of peptides and proteins are quite limited. The aim of this work was to develop and evaluate a water-in-oil (w/o) microemulsion system in vitro and in vivo for local intestinal delivery of water-soluble peptides after oral administration. A fluorescent labeled peptide, 5-(and-6)-carboxytetramethylrhodamine labeled HIV transactivator protein TAT (TAMRA-TAT), was used as a model peptide. Water-in-oil microemulsions consisting of Miglyol 812, Capmul MCM, Tween 80, and water were developed and characterized in terms of appearance, viscosity, conductivity, morphology, and particle size analysis. TAMRA-TAT was loaded and its enzymatic stability was assessed in modified simulated intestinal fluid (MSIF) in vitro. In in vivo studies, TAMRA-TAT intestinal distribution was evaluated using fluorescence microscopy after TAMRA-TAT microemulsion, TAMRA-TAT solution, and placebo microemulsion were orally gavaged to mice. The half-life of TAMRA-TAT in microemulsion was enhanced nearly three-fold compared to that in the water solution when challenged by MSIF. The treatment with TAMRA-TAT microemulsion after oral administration resulted in greater fluorescence intensity in all intestine sections (duodenum, jejunum, ileum, and colon) compared to TAMRA-TAT solution or placebo microemulsion. The in vitro and in vivo studies together suggested TAMRA-TAT was better protected in the w/o microemulsion in an enzyme-containing environment, suggesting that the w/o microemulsions developed in this study may serve as a potential delivery vehicle for local intestinal delivery of peptides or proteins after oral administration.

Authors and Affiliations

Dongyun Liu, Taku Kobayashi, Steven Russo, Fengling Li, Scott E. Plevy, Todd M. Gambling, Johnny L. Carson, Russell J. Mumper

Keywords

Related Articles

Mixed Effects Modeling Using Stochastic Differential Equations: Illustrated by Pharmacokinetic Data of Nicotinic Acid in Obese Zucker Rats

Inclusion of stochastic differential equations in mixed effects models provides means to quantify and distinguish three sources of variability in data. In addition to the two commonly encountered sources, measurement err...

Drug–Drug Interaction Studies: Regulatory Guidance and An Industry Perspective

The online version of this article (doi:10.1208/s12248-013-9470-x) contains supplementary material, which is available to authorized users.

Large Molecule Run Acceptance: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

The L1 Global Harmonization Team provides recommendations specifically for run acceptance of ligand binding methods used in bioanalysis of macromolecules in support of pharmacokinetics. The team focused on standard curve...

Empirical and Semi-Mechanistic Modelling of Double-Peaked Pharmacokinetic Profile Phenomenon Due to Gastric Emptying

Models have been developed to explain double-peaked plasma concentration-time profiles using mechanisms such as variable absorption and enterohepatic recirculation. Interruption of gastric emptying has also been shown to...

Determination of the Most Influential Sources of Variability in Tacrolimus Trough Blood Concentrations in Adult Liver Transplant Recipients: A Bottom-Up Approach

The online version of this article (doi:10.1208/s12248-014-9577-8) contains supplementary material, which is available to authorized users.

Download PDF file
  • EP ID EP681765
  • DOI  10.1208/s12248-012-9441-7
  • Views 78
  • Downloads 0

How To Cite

Dongyun Liu, Taku Kobayashi, Steven Russo, Fengling Li, Scott E. Plevy, Todd M. Gambling, Johnny L. Carson, Russell J. Mumper (2013). In Vitro and In Vivo Evaluation of a Water-in-Oil Microemulsion System for Enhanced Peptide Intestinal Delivery. The AAPS Journal, 15(1), -. https://www.europub.co.uk/articles/-A-681765