Influence of polymer structure upon active-ingredient loading: a Monte Carlo simulation study for design of drug-delivery devices

Drug-loaded polymers and polymeric microparticles provide an attractive for m for controlled drug-delivery systems. Design of new systems requires know ledge of polymer-drug interactions. The effect of polymer architecture and chemistry upon active-ingredient loading is investigated by Monte Carlo sim ulation. The ensemble-growth method is used to sample conformations of a mo del polymer comprising polar and nonpolar segments. The polymer is a block copolymer, linear or branched. In our calculations, the polar portion of th e polymer contains 21 segments. The polymers are dissolved in either of two types of solvent models, In the first, nonpolar solvent, the polar segment s tend to collapse, but the bulky nonpolar groups, easily soluble in the me dium, create some cavities in the polymer. These cavities are suitable host s for the slightly polar active ingredient. In the second solvent, polar, t he nonpolar segments contribute to attract the active ingredient within the polymer segments, therefore lowering the burst-release rate. The relative uptake of the active ingredient, proportional to the probability of finding an active ingredient within the radius of gyration of the polymer, is comp uted as a function of the number of nonpolar segments in the polymer. Simul ation results are reported for active ingredients of two different sizes. F or given size of the polar portion, short nonpolar tails increase the activ e-ingredient relative uptake in both solvents considered. Linear block copo lymers look promising for obtaining higher entrapment efficiency for the ac tive ingredient and for controlled release. (C) 2001 Elsevier Science B.V. All rights reserved.