César Soto-Figueroa

Mesoscopic simulation of the drug release mechanism on the polymeric vehicle P(ST-DVB) in an acid environment

In this work, the drug release mechanism of a polymeric delivery vehicle (polymeric microsphere) is investigated using dissipative particle dynamics (DPD) simulations. Polymer nanoparticles are interesting drug-delivery systems because drugs can be encapsulated inside the shell, which exhibits swelling properties that depend on pH conditions. Albendazole is selected as the model drug, whereas poly(styrene-divinylbenzene) P(ST-DVB) copolymer is the carrier. The DPD simulation shows that drug release of the P(ST-DVB) carrier in an acidic environment occurs via a diffusion mechanism (swelling followed by diffusion). Four transient stages were detected during the drug release: (i) swelling of the polymeric microsphere, (ii) the generation of pores, (iii) drug diffusion in the polymeric matrix and (iv) drug release towards the acid medium. All transient states of the drug release process of the polymeric carrier in an acid environment are described and analysed in this paper. The outcomes obtained from the DPD simulations are consistent with the available experimental results, and they provide a mesoscopic methodology for the evaluation and prediction of new advanced polymeric carriers of pharmaceutical interest.

Dissipative particle dynamics simulation of the micellization–demicellization process and micellar shuttle of a diblock copolymer in a biphasic system (water/ionic-liquid)

We simulated the thermoreversible micellization–demicellization process and micellar shuttle of a poly(N-isopropylacrylamide-block-ethylene-oxide) (PNIPAM–PEO) diblock copolymer in a water/ionic-liquid (1-butyl-3-methylimidazolium hexafluorophosphate, [BMIM][PF6]) system by means of dissipative particle dynamics (DPD). The evolution of diblock copolymer chains (micellization–transfer–demicellization) in both water and the ionic liquid phase by the temperature effect reveals that it is a physical phenomenon, dependent on the solubility and interaction parameters of all chemical species involved in the multicomponent system. With the aid of a Monte Carlo simulation we calculated the Flory–Huggins interaction parameters χ of all the species. At room temperature the PNIPAM–PEO copolymer chains are miscible in the aqueous phase. At a higher temperature of T = 303 K the diblock copolymer shows the formation of micelles (micellization process). The micellar transfer to the ionic liquid phase was observed at T = 333 K. A further increase in temperature provokes the demicellization at T = 346 K. The process is reversible: reversing the temperature now to 333 K, shows the formation of the micelles. A further decrease in temperature makes the micelles go back to the water phase. All the simulation outcomes are qualitatively consistent with the experimental results, demonstrating that the DPD methodology may provide a tool for the investigation and analysis of the micellar transfer process in immiscible environments.

Molecular and mesoscopic study of ionic liquids and their use as solvents of active agents released by polymeric vehicles

This work explores the diffusivity of the drug albendazole contained in a polymeric vehicle, Styrene-Divinylbenzene (ST-DVD), when it is subject to different environments. The environments consist of water and three different ionic liquids. First, the solubility parameters of these ionic liquids, [BMIM][PF6], [HMIM][Br] and [BMIM][BF4], and albendazole were evaluated by means of molecular dynamics employing COMPASS force-field and a NPT ensemble at 298 K. Then a mesoscopic simulation using Dissipative Particle Dynamics (DPD) was used. In the presence of ionic liquids the albendazole exhibits a diffusivity in [BMIM][PF6] around ten times that shown in [BMIM][BF4] or [HMIM][Br]. This is connected with the corresponding solvent power. The results obtained from these molecular and mesoscopic simulations are consistent with reported experimental results and are useful to predict and evaluate the solvent power of ionic liquids applied to drugs of pharmaceutical use.

Thermal Study on Phase Transitions of Block Copolymers by Mesoscopic Simulation

The block copolymers are an exceptional kind of macromolecules constituted by two or more blocks of different homopolymer chains linked by covalent bonds. These polymeric materials have received much attention over past few years due in large part to their ability to selfassemble in the melted state or in a selective solvent inside a variety of ordered phases or welldefined structures of high regularity in size and shape with characteristic dimensions between 100 and 500 nanometres. These ordered phases and their structural modification are the key to many valuable physical properties which make block copolymers of great industrial and technological interest. The molecular self-assemble and formation of periodic phases in the block copolymers depend of the strength of interblock repulsion and composition, for example, mesoscopic studies of the poly(styrene)-poly(isoprene) (PS-PI) diblock copolymer, have demonstrated that this synthetic material, may generate a series of long-range ordered microdomains when exist a weak repulsion between the unlike monomers isoprene and styrene, as result, the PS-PI diblock copolymer chains tend to segregate below some critical temperature, but, as they are linked by covalent bonds, the phase separation on a macroscopic level is prevented, only a local microphase segregation occurs (Soto-Figueroa et al., 2005, SotoFigueroa et al., 2007). The phase transition from homogeneous state of polymeric chains to an ordered state with periodic phases is called microphase separation transition (MST) or orderdisorder phase transition (ODT) (Leibler, 1980). The phase segregation and generation of ordered structures in the microscopic level of a diblock copolymer via an order-disorder phase transition is illustrated in Fig. 1.