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

Solvation and hydration characteristics of ibuprofen and acetylsalicylic acid

Ibuprofen and acetylsalicylic acid were studied by thermoanalytical methods: sublimation calorimetry, solution calorimetry, and with respect to solubility. Upon measuring the temperature dependences of the saturated vapo...

Clinical Immunogenicity of rHuPH20, a Hyaluronidase Enabling Subcutaneous Drug Administration

The online version of this article (doi:10.1208/s12248-015-9782-0) contains supplementary material, which is available to authorized users.

Ligand Binding Assays in the 21st Century Laboratory: Platforms

A high level of precision is required to generate reproducible bioanalytical results for the measurement of drug, biomarker concentrations, and detection of immunogenic responses. Precision for LBAs analytical assays use...

Comparison of Methods for Handling Missing Covariate Data

Missing covariate data is a common problem in nonlinear mixed effects modelling of clinical data. The aim of this study was to implement and compare methods for handling missing covariate data in nonlinear mixed effects...

Ethinyl Estradiol and Other Human Pharmaceutical Estrogens in the Aquatic Environment: A Review of Recent Risk Assessment Data

Interest in pharmaceuticals in the environment has increased substantially in recent years. Several studies in particular have assessed human and ecological risks from human pharmaceutical estrogens, such as 17α-...

Download PDF file
  • EP ID EP681765
  • DOI  10.1208/s12248-012-9441-7
  • Views 68
  • 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://europub.co.uk/articles/-A-681765