Adhesion of microorganisms to bovine submaxillary mucin coatings: effect of coating deposition conditions

The adhesion of Staphylococcus epidermidis, Escherichia coli, and Candida albicans on mucin coatings has been evaluated to explore the feasibility of the coating to increase the infection resistance of biomaterials. Coatings of bovine submaxillary mucin (BSM) were deposited on a base layer consisting of a poly(acrylic acid-b-methyl methacrylate) (PAA-b-PMMA) diblock copolymer. This bi-layer system exploits the mucoadhesive interactions of the PAA block to aid the adhesion of mucin to the substrate, whereas the PMMA block prevents the coating's dissolution in aqueous environments. The thickness of the mucin coating was adjusted by varying the pH of the solution from which it was deposited. Thin mucin coatings decreased the numbers of bacteria but increased the numbers of C. albicans adhering to the copolymer and control surfaces. Increasing the mucin film thickness resulted in a further lowering of the number density of adhering S. epidermidis cells, but it did not affect the number density of E. coli. In contrast, the C. albicans number densities increased with an increased mucin thickness

Developing and characterising mucin films and evaluating them as a bacteria resistant coating.

Mucin is a naturally occurring polymer that belongs to the glycoprotein family. It is an amphiphilic molecule made of two main parts: a hydrophobic protein backbone and hydrophilic carbohydrate side chains. As a result of this structure, it can adsorb on many types of surfaces to create a hydrophilic, lubricating layer. Mucin has been shown in recent studies to have the potential to suppress the adhesion of bacteria. The aim of this study is to develop a uniform mucin coating resistant to bacterial adhesion. In developing a coating technique, we created a multi-layer system consisting of a poly(acrylic acid) (PAA) copolymer as a base layer and a mucin layer on top, as this exploits the mucoadhesion interactions between PAA and mucin in bonding to the base. The mucin coatings created were then evaluated against the adhesion of microorganisms, including two species of bacteria (Staphylococcus epidermidis and Escherichia coli) and one species of yeast (Candida albicans) known to be problematic for patients inserted with urinary catheters. This study develops as the following: oExperimental work was conducted on the creation of the mucin coating using poly(aciylic acid)-b-poly(methyl methacrylate) as a base coating and poly(methyl methacrylate) and silicon as controls. The effect of pH was used as a means to control the mucin layer thickness, where a thicker mucin layer was adsorbed on the copolymer from acidic mucin solutions than neutral and basic mucin solutions. Roughness and surface energy measurements revealed smoother and more hydrophilic surfaces created from the thicker mucin layers. oInfrared spectroscopic ellipsometiy was used to study the interfacial bonding between the copolymer layer and the adsorbed mucin layer. This study showed that at pH 3 more hydrogen bonds were created between PAA-b-PMMA and mucin. It also showed conformational changes in the protein backbone of mucin at lower pH. oIn evaluating the adhesion of microorganisms on the mucin coating, through direct counting, we saw a decrease in bacterial adhesion after mucin coating compared to the bare surfaces but no effect on the adhesion of yeast cells. Increasing the mucin coating thickness further reduced the numbers of Staphylococcus epidermidis but not Escherichia coli

Developing and characterising mucin films and evaluating them as a bacteria resistant coating.

Mucin is a naturally occurring polymer that belongs to the glycoprotein family. It is an amphiphilic molecule made of two main parts: a hydrophobic protein backbone and hydrophilic carbohydrate side chains. As a result of this structure, it can adsorb on many types of surfaces to create a hydrophilic, lubricating layer. Mucin has been shown in recent studies to have the potential to suppress the adhesion of bacteria. The aim of this study is to develop a uniform mucin coating resistant to bacterial adhesion. In developing a coating technique, we created a multi-layer system consisting of a poly(acrylic acid) (PAA) copolymer as a base layer and a mucin layer on top, as this exploits the mucoadhesion interactions between PAA and mucin in bonding to the base. The mucin coatings created were then evaluated against the adhesion of microorganisms, including two species of bacteria (Staphylococcus epidermidis and Escherichia coli) and one species of yeast (Candida albicans) known to be problematic for patients inserted with urinary catheters. This study develops as the following: oExperimental work was conducted on the creation of the mucin coating using poly(aciylic acid)-b-poly(methyl methacrylate) as a base coating and poly(methyl methacrylate) and silicon as controls. The effect of pH was used as a means to control the mucin layer thickness, where a thicker mucin layer was adsorbed on the copolymer from acidic mucin solutions than neutral and basic mucin solutions. Roughness and surface energy measurements revealed smoother and more hydrophilic surfaces created from the thicker mucin layers. oInfrared spectroscopic ellipsometiy was used to study the interfacial bonding between the copolymer layer and the adsorbed mucin layer. This study showed that at pH 3 more hydrogen bonds were created between PAA-b-PMMA and mucin. It also showed conformational changes in the protein backbone of mucin at lower pH. oIn evaluating the adhesion of microorganisms on the mucin coating, through direct counting, we saw a decrease in bacterial adhesion after mucin coating compared to the bare surfaces but no effect on the adhesion of yeast cells. Increasing the mucin coating thickness further reduced the numbers of Staphylococcus epidermidis but not Escherichia coli

Engineered peptides with enzymatically cleavable domains for controlling the release of model protein drug from \u201csoft\u201d nanoparticles

Matrix metalloproteinase-2 (MMP-2) is an endopeptidase that has been shown to be present in high concentrations during most tissue remodeling events, including disease states like active tumor sites, thus making it an attractive molecule for use in effecting local delivery of therapeutic molecules. Moreover, the use of non-toxic and biodegradable nanoparticles for controlled drug delivery is highly sought after. To this end, bovine serum albumin (BSA) nanoparticles (NPs) were stabilized with coatings formed using domains of varying sensitivity to MMP-2, viz. K6GPQG/IASQK6 and K6HPVG/LLARK6, lysine residues being used to facilitate peptide immobilization to the BSA NPs via electrostatic interactions, and peptide domains that have a high (HPVG/LLAR) and low (GPQG/IASQ) MMP-2 cleavage rate. The MMP-2-induced cleavage rates of these two domains (the position of action being noted with a \u201c/\u201d) have differing kinetics that can be used to provide a novel mechanism for facilitating the controlled release of molecules where local concentrations of MMP-2 are high. It was found that both surface concentration and cleavage domain type influenced the release of the model drug (BSA) from these NPs. This stratagem may provide a novel pathway for developing multi-functional coatings for controlling the local delivery of therapeutics at sites where the presence of various enzymes exist as a function of tissue state.Peer reviewed: YesNRC publication: Ye

Therapeutics discovery: From bench to first in-human trials

The ‘Therapeutics discovery: From bench to first in-human trials’ conference, held at the King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Kingdom of Saudi Arabia (KSA) from October 10-12, 2017, provided a unique opportunity for experts worldwide to discuss advances in drug discovery and development, focusing on phase I clinical trials. It was the first event of its kind to be hosted at the new research center, which was constructed to boost drug discovery and development in the KSA in collaboration with institutions, such as the Academic Drug Discovery Consortium in the United States of America (USA), Structural Genomics Consortium of the University of Oxford in the United Kingdom (UK), and Institute of Materia Medica of the Chinese Academy of Medical Sciences in China. The program was divided into two parts. A pre‑symposium day took place on October 10, during which courses were conducted on clinical trials, preclinical drug discovery, molecular biology and nanofiber research. The attendees had the opportunity for one-to-one meetings with international experts to exchange information and foster collaborations. In the second part of the conference, which took place on October 11 and 12, the clinical trials pipeline, design and recruitment of volunteers, and economic impact of clinical trials were discussed. The Saudi Food and Drug Administration presented the regulations governing clinical trials in the KSA. The process of preclinical drug discovery from small molecules, cellular and immunologic therapies, and approaches to identifying new targets were also presented. The recommendation of the conference was that researchers in the KSA must invest more fund, talents and infrastructure to lead the region in phase I clinical trials and preclinical drug discovery. Diseases affecting the local population, such as Middle East Respiratory Syndrome and resistant bacterial infections, represent the optimal starting point