In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide.

BACKGROUND: The aim of the study was to develop an oral self-emulsifying drug delivery system (SEDDS) for exenatide and to evaluate its in vivo efficacy. METHODS: Exenatide was lipidised via hydrophobic ion pairing with sodium docusate (DOC) and incorporated in SEDDS consisting of 35% Cremophor EL, 25% Labrafil 1944, 30% Capmul-PG 8 and 10% propylene glycol. Exenatide/DOC was characterized in terms of lipophilicity evaluating the octanol/water phase distribution (logP). Exenatide/DOC SEDDS were characterized via droplet size analysis, drug release characteristics (log DSEDDS/release medium determination) and mucus permeation studies. Furthermore, the impact of orally administered exenatide/DOC SEDDS on blood glucose level was investigated in vivo on healthy male Sprague-Dawley rats. RESULTS: Hydrophobic ion pairing in a molar ratio of 1:4 (exenatide:DOC) increased the effective logP of exenatide from -1.1 to 2.1. SEDDS with a payload of 1% exenatide/DOC had a mean droplet size of 45.87 ±â€¯2.9 nm and a Log DSEDDS/release medium of 1.9 ±â€¯0.05. Permeation experiments revealed 2.7-fold improved mucus diffusion for exenatide/DOC SEDDS compared to exenatide in solution. Orally administered exenatide/DOC SEDDS showed a relative bioavailability (versus s.c.) of 14.62% ±â€¯3.07% and caused a significant (p < .05) 20.6% decrease in AUC values of blood glucose levels. CONCLUSION: According to these results, hydrophobic ion pairing in combination with SEDDS represents a promising tool for oral peptide delivery.

Enzyme decorated drug carriers: Targeted swords to cleave and overcome the mucus barrier.

The use of mucus permeating drug carrier systems being able to overcome the mucus barrier can lead to a remarkable enhancement in bioavailability. One promising approach is the design of mucolytic enzyme decorated carrier systems (MECS). These systems include micro- and nanoparticles as well as self-emulsifying drug delivery systems (SEDDS) decorated with mucin cleaving enzymes such as papain (PAP) or bromelain (BRO). MECS are able to cross the mucus barrier in a comparatively efficient manner by cleaving mucus substructures in front of them on their way to the epithelium. Thereby these enzymes hydrolyze peptide bonds of mucus glycoproteins forming tiny holes or passages through the mucus. In various in vitro and in vivo studies MECS proved to be superior in their mucus permeating properties over nanocarriers without enzyme decoration. PAP decorated nanoparticles, for instance, remained 3h after oral administration to an even 2.5-fold higher extend in rat small intestine than the corresponding undecorated nanoparticles permeating the intestinal mucus gel layer to a much lower degree. As MECS break up the mucus network only locally without destroying its overall protective barrier function, even long term treatments with such systems seem feasible. Within this review article we address different drug carrier systems decorated with various types of enzymes, their particular pros and cons and potential applications.

Design, modification and in vitro evaluation of pectin's bucco-adhesiveness.

AIM: It was the aim of this study to synthesize pectin (PEC) with sulfhydryl groups and evaluate its suitability in buccal application. MATERIALS & METHODS: Native PEC was chemically modified by covalent attachment of sulfhydryl-bearing cysteine (CYS). Stability assays in form of water uptake behavior and erosion study were performed. Additionally, mucoadhesive study on buccal mucosa was performed. RESULTS: Pectin-cysteine (PECCYS) was successfully synthesized as proved by IR and Ellman's assay exhibiting 436.59 ± 127.87 µmol thiol groups per gram polymer. Stability assay showed that PECCYS revealed a 2.27-fold improved water uptake and mucoadhesiveness augmented 3.75-fold in comparison to unmodified PEC. CONCLUSION: PECCYS might be a future suitable excipient for buccal adhesive application.