Quantitative multi-agent models for simulating protein release from PLGA bioerodible nano- and microspheres

Abstract

Summary. Using poly(lactide-co-glycolide) (PLGA) particles for drug encapsulation and delivery has recently gained considerable popularity for a number of reasons. An advantage in one sense, but a drawback of PLGA use in another, is that drug delivery systems made of this material can provide a wide range of dissolution profiles, due to their internal structure and properties related to particles' manufacture. The advantages of enriching particulate drug design experimentation with computer models, are evident with simulations used to predict and optimize design, as well as indicate choice of best manufacturing parameters. In the present work, we seek to understand the phenomena observed for PLGA micro-and nanospheres, through Cellular Automata (CA) agent-based Monte Carlo (MC) models. Systems are studied both over large temporal scales, (capturing slow erosion of PLGA) and for various spatial configurations (capturing initial as well as dynamic morphology). The major strength of this multi-agent approach is to observe dissolution directly, by monitoring the emergent behaviour: the dissolution profile manifested, as a sphere erodes. Different problematic aspects of the modelling process are discussed in details in this paper. The models were tested on experimental data from literature, demonstrating very good performance. Quantitative discussion is provided throughout the text in order to make a demonstration of the use in practice of the proposed model.

Lifetime prediction of biodegradable polymers

“…Another method that has been adopted for the modelling of bulk polymer degradation is a cellular automaton approach, which is a discrete dynamic modelling approach, similar to and extended from the Monte Carlo process, based on a virtual matrix defined in a cubic space, with a number of states being modelled (such as polymer, solvent, porosity, solid drug or drug in its solubilised form) [143][144][145]. The life expectancy of a polymer cell (its probability of being eroded) changes as the number of direct neighbour cells containing solvent changes.…”

Application of Response Surface Methodology in the Preparation of Pectin-Caseinate Nanocomplexes for Potential Use as Nutraceutical Formulation: A Statistical Experimental Design Analysis

“…Biopolymer based nanocomplexs could be potentially used as nanocarriers to encapsulate and deliver bioactive or functional components, such as hydrophobic nutraceuticals (e.g, fat-soluble vitamins, antioxidants, carotenoids, phytosterols and polyunsaturated fatty acids) minerals, active peptides, enzymes and antimicrobial compounds. [3][4][5][6] Creation of nanocarriers for bioactive components may increase their bioavailability, due to their nanoscopic size and enormous numbers per unit mass, reduce adverse effects such as transparency of clear food systems like beverages, offer protection against degradation of the nutraceuticals by chemical and enzymatic reactions like oxidation during manufacturing and shelf-life, hence inhibiting of increasing of unwanted flavors and odors, as well as loss of metabolic value. 7 Among the several natural or synthetic polymer-based nanoparticle which are potentially available to the food industry, protein-based nanoparticles are generally interesting since they are fairly easy to use and their size distribution can be observed.…”

Computational Intelligence Modeling of the Macromolecules Release from PLGA Microspheres—Focus on Feature Selection

“…During the last decade, research for elucidation of macromolecular drugs release mechanism from PLGA-based drug delivery systems were in focus [ 4 – 7 ]. Most of the work is based on mathematical modeling [ 4 , 5 , 8 , 9 ]. Only a few are directly related to the usage of heuristic computational techniques for knowledge extraction [ 10 , 11 ].…”