Jérôme G J L Lebouille

Controlled nanoparticle formation by diffusion limited coalescence

Polymeric nanoparticles (NPs) have great application potential in science and technology. Their functionality strongly depends on their size. We present a theory for the size of NPs formed by precipitation of polymers into a bad solvent in the presence of a stabilizing surfactant. The analytical theory is based upon diffusion-limited coalescence kinetics of the polymers. Two relevant time scales, a mixing and a coalescence time, are identified and their ratio is shown to determine the final NP diameter. The size is found to scale in a universal manner and is predominantly sensitive to the mixing time and the polymer concentration if the surfactant concentration is sufficiently high. The model predictions are in good agreement with experimental data. Hence the theory provides a solid framework for tailoring NPs with a priori determined size.

Controlled block copolymer micelle formation for encapsulation of hydrophobic ingredients

We report on the formation of polymeric micelles in water using triblock copolymers with a polyethylene glycol middle block and various hydrophobic outer blocks prepared with the precipitation method. We form micelles in a reproducible manner with a narrow size distribution. This suggests that during the formation of the micelles the system had time to form micelles under close-to-thermodynamic control. This may explain why it is possible to use an equilibrium self-consistent field theory to predict the hydrodynamic size and the loading capacity of the micelles in accordance with experimental finding. Yet, the micelles are structurally quenched as concluded from the observation of size stability in time. We demonstrate that our approach enables to prepare rather hydrophobic block copolymer micelles with tunable size and loading.Graphical abstract

Formulation and antifungal performance of natamycin-loaded liposomal suspensions: the benefits of sterol-enrichment.

Abstract The aim of this study is to develop and evaluate food-grade liposomal delivery systems for the antifungal compound natamycin. Liposomes made of various soybean lecithins are prepared by solvent injection, leading to small unilamellar vesicles (<130 nm) with controlled polydispersity, able to encapsulate natamycin without significant modification of their size characteristics. Presence of charged phospholipids and reduced content of phosphatidylcholine in the lecithin mixture are found to be beneficial for natamycin encapsulation, indicating electrostatic interactions of the preservative with the polar head of the phospholipids. The chemical instability of natamycin upon storage in these formulations is however significant and proves that uncontrolled leakage out of the liposomes occurs. Efficient prevention of natamycin degradation is obtained by incorporation of sterols (cholesterol, ergosterol) in the lipid mixture and is linked to higher entrapment levels and reduced permeability of the phospholipid membrane provided by the ordering effect of sterols. Comparable action of ergosterol is observed at concentrations 2.5-fold lower than cholesterol and attributed to a preferential interaction of natamycin–ergosterol as well as a higher control of membrane permeability. Fine-tuning of sterol concentration allows preparation of liposomal suspensions presenting modulated in vitro release kinetics rates and enhanced antifungal activity against the model yeast Saccharomyces cerevisiae.

Self-consistent field predictions for quenched spherical biocompatible triblock copolymer micelles

We have used the Scheutjens–Fleer self-consistent field (SF-SCF) method to predict the self-assembly of triblock copolymers with a solvophilic middle block and sufficiently long solvophobic outer blocks. We model copolymers consisting of polyethylene oxide (PEO) as the solvophilic block and poly(lactic-co-glycolic) acid (PLGA) or poly(e-caprolactone) (PCL) as the solvophobic block. These copolymers form structurally quenched spherical micelles provided the solvophilic block is long enough. Predictions are calibrated on experimental data for micelles composed of PCL-PEO-PCL and PLGA-PEO-PLGA triblock copolymers prepared via the nanoprecipitation method. We establish effective interaction parameters that enable us to predict various micelle properties such as the hydrodynamic size, the aggregation number and the loading capacity of the micelles for hydrophobic species that are consistent with experimental findings.