Do interactions between Protein and Phospholipids influence the release behavior from lipid-based exenatide depot systems?

08:00 EDT 10th June 2019 | BioPortfolio

Summary of "Do interactions between Protein and Phospholipids influence the release behavior from lipid-based exenatide depot systems?"

The release mechanism for proteins and peptides from vesicular phospholipid gels (VPGs) is very complex. Drug release proceeds via a combination of erosion of the gel and diffusion of the drug out of it. This diffusion can be retarded by a slow permeation of the drug across the lipid bilayers in the gel as well as by its direct binding or adsorption to the lipid bilayers. Finally, the viscosity and homogeneity of the formulation may affect the release behavior. So far a direct correlation between one of these parameters and the release kinetics is not possible. In the present study, we aimed to investigate the contribution of drug-membrane interactions to the release kinetics of exenatide from differently composed VPGs (POPC, POPG and mixtures of both). To this end, in vitro release of exenatide as well as in vitro release of the phospholipids was monitored. Binding affinities were determined by microscale thermophoresis (MST). The sustained release behavior of exenatide could not simply be correlated to high viscosity of the VPG formulation. Release of exenatide from VPGs of anionic membranes containing POPG proceeded with a half-life of the order of 5 days and it seems to be controlled by the erosion of the gel. Its rate is unaffected by the initial pH inside the gel, independently of the strong impact of pH on exenatide binding to the membrane. At pH 4.5, exenatide is cationic and binds to membranes containing anionic POPG with a high affinity (K ≈ 10-30µM). No high affinity membrane binding of exenatide is detected in this at pH 7.4, where exenatide is anionic, and to zwitterionic membranes composed of POPC. Exenatide release from the latter has a significantly longer half-life of 30to55 days. That means, these VPGs are much more resistant to erosion and show a very slow diffusional release. In this case, diffusion should be slowed down by the barrier function of the membranes rather than membrane affinity. In conclusion, erosion of the VPG matrix and membrane permeability of the drug are the major parameters influencing the release of exenatide from VPGs of POPC-POPG, whereas drug binding to the membranes had a minor effect only.


Journal Details

This article was published in the following journal.

Name: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
ISSN: 1873-3441


DeepDyve research library

PubMed Articles [26290 Associated PubMed Articles listed on BioPortfolio]

Computational Analysis of Protein-Protein Interactions in Motile T-Cells.

Analysis of protein-protein interactions is important for better understanding of molecular mechanisms involved in immune regulation and has potential for elaborating avenues for drug discovery target...

Possibilities and Limitations of Different Separation Techniques for the Analysis of the Protein Corona.

One of the biggest challenges in the field of nanomedicine is the adsorption of biomolecules on the nanomaterial upon contact with a biological medium. The interactions of the so formed protein corona...

Transient Gene Expression as a Tool to Monitor and Manipulate the Levels of Acidic Phospholipids in Plant Cells.

Anionic phospholipids represent only minor fraction of cell membranes lipids but they are critically important for many membrane-related processes, including membrane identity, charge, shape, the gene...

Distribution of ionizable groups in polyampholyte microgels controls interactions with captured proteins: from blockade and "levitation" to accelerated release.

A striking discovery in our work is that the distribution of ionizable groups in polyampholyte microgels (random and core-shell) controls the interactions with the captured proteins. Polyampholyte mic...

Selection of Protein-Protein Interactions of Desired Affinities with a Bandpass Circuit.

We have developed a genetic circuit in Escherichia coli that can be used to select for protein-protein interactions of different strengths by changing antibiotic concentrations in the media. The genet...

Clinical Trials [9007 Associated Clinical Trials listed on BioPortfolio]

Register of Patients With Anti-Phospholipids Syndrome (APS) and/or Systemic Lupus Erythematosus (SLE)

The purpose of that register is to collect medical information about patients suffering of APS with or without associated SLE.

Time Together: A Multi-site Nursing Intervention Project Using a Single System Experimental Design

The aim of this project is to test and evaluate a nursing intervention, Time Together (TT), created to enable quality interactions between patients and staff in psychiatric inpatient care....

Project Options - The ABC Method

The present study explores the ability of dermatologists to influence patients' behavior using a novel and brief (3 minute) behavioral intervention in the context of naturally occurring pa...

Safety Assessment of Potential Interactions Between IV Methamphetamine and Osmotic-Release Methylphenidate (OROS-MPH)

This is a human inpatient clinical pharmacology study to assess potential interactions between intravenous (i.v.) methamphetamine infusion and oral osmotic release methylphenidate (OROS-MP...

Gene Polymorphisms in Tacrolimus Drug Interactions

A retrospective analysis of the influence of gene polymorphisms on drug interactions between calcineurin-inhibitors and concomitant drugs in renal transplant patients.

Medical and Biotech [MESH] Definitions

Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.

An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.

A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.

A protein that accounts for more than half of the peripheral nervous system myelin protein. The extracellular domain of this protein is believed to engage in adhesive interactions and thus hold the myelin membrane compact. It can behave as a homophilic adhesion molecule through interactions with its extracellular domains. (From J Cell Biol 1994;126(4):1089-97)

The effect or sway that a PEER GROUP exerts on the beliefs, value systems and behavior of each member of a group. The social expectations for individuals to conform to peer group influence is known as peer pressure.

Quick Search


DeepDyve research library

Relevant Topics

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Searches Linking to this Article