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

A Report from the Pediatric Formulations Task Force: Perspectives on the State of Child-Friendly Oral Dosage Forms

Despite the fact that a significant percentage of the population is unable to swallow tablets and capsules, these dosage forms continue to be the default standard. These oral formulations fail many patients, especially c...

Comparison of Neutralizing Antibody Assays for Receptor Binding and Enzyme Activity of the Enzyme Replacement Therapeutic Naglazyme® (Galsulfase)

Most patients receiving Naglazyme® (galsulfase, rhASB) enzyme replacement therapy for mucopolysaccharidosis type VI develop an antibody response. To evaluate the impact of this response, two in vitro neutralizing...

Neuro-fuzzy Models as an IVIVR Tool and Their Applicability in Generic Drug Development

The online version of this article (doi:10.1208/s12248-014-9569-8) contains supplementary material, which is available to authorized users.

Modeling, Simulation, and Translation Framework for the Preclinical Development of Monoclonal Antibodies

The industry-wide biopharmaceutical (i.e., biologic, biotherapeutic) pipeline has been growing at an astonishing rate over the last decade with the proportion of approved new biological entities to new chemical entities...

High-Throughput Biophysical Analysis of Protein Therapeutics to Examine Interrelationships Between Aggregate Formation and Conformational Stability

Stabilization and formulation of therapeutic proteins against physical instability, both structural alterations and aggregation, is particularly challenging not only due to each protein’s unique physicochemical c...

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