Investigating the release of a hydrophobic peptide from matrices of biodegradable polymers: An integrated method approach

Abstract

The objectives of this work were: (1) to select suitable compositions of tyrosine-derived polycarbonates for controlled delivery of voclosporin, a potent drug candidate to treat ocular diseases, (2) to establish a structure-function relationship between key molecular characteristics of biodegradable polymer matrices and drug release kinetics, and (3) to identify factors contributing in the rate of drug release. For the first time, the experimental study of polymeric drug release was accompanied by a hierarchical sequence of three computational methods. First, suitable polymer compositions used in subsequent neural network modeling were determined by means of response surface methodology (RSM). Second, accurate artificial neural network (ANN) models were built to predict drug release profiles for fifteen polymers located outside the initial design space. Finally, thermodynamic properties and hydrogen-bonding patterns of model drug-polymer complexes were studied using molecular dynamics (MD) technique to elucidate a role of specific interactions in drug release mechanism. This research presents further development of methodological approaches to meet challenges in the design of polymeric drug delivery systems.

The Effect of Plasma Pretreatment and Cross-Linking Degree on the Physical and Antimicrobial Properties of Nisin-Coated PVA Films

“…Mainly in the samples with 40% crosslinking degree, modest antibacterial activity of GA in the systems has been found. However, this factor does not represent significant contribution to antibacterial activity of the PVA/GA/nisin samples [ 17 , 45 ]. Therefore, nisin is be supposed to be the principal antibacterial agent against G+ bacterial strains in the studied systems.…”

“…Nisin layers were tested as promising natural coating with anti-staphylococcal activity [ 6 , 9 , 11 , 17 , 18 ], and it was proved that even in combination with PVA surface, it can improve the antimicrobial activity of biocompatible films. Nevertheless, the key role lies in the plasma treatment, as was confirmed for other polymer materials in literature [ 16 , 19 , 22 , 29 ].…”

“…Nisin is an amphiphilic peptide (bacteriocin) with low molecular weight (approximately 3.4 kDa) that is an effective inhibitor of Gram-positive bacterial strains [ 9 , 10 , 13 , 14 , 15 , 16 ], which are produced by lactic acid bacterial strain Lactococcus lactis during the fermentation process. Nisin has been studied as a promising preserving agent since the 1950s [ 17 , 18 ]. Moreover, nisin (and another bacteriocins) provide sufficient antimicrobial activity against bacterial strains that are resistant to conventional drugs.…”

Preparation of Drug Eluting Natural Composite Scaffold Using Response Surface Methodology and Artificial Neural Network Approach

“…Artificial Neural Network (ANN) can overcome the limitation of RSM in predicting non-linear system. ANN is a model-independent method which can efficiently capture the nonlinearity in responses associated with drug release from polymer matrices [10].…”

Developing a Suitable Model for Water Uptake for Biodegradable Polymers Using Small Training Sets

“…Even Le et al (2013), who built predictions of phase behavior over time, developed the model using each experimental value as a single input, without considering how the phase behavior changes over time [ 39 ]. Previously, we built ANN models to accurately predict drug release over time on a family of terpolymers [ 40 ] using molecular descriptors. In this study, we develop and compare models for water uptake over time, first using all individual data separately and then using a global parameter for this property.…”