Biopolymer Micro/Nanogel Particles as Smart Drug Delivery and Theranostic Systems.

In recent years, micro/nanogels have become an important topic of interdisciplinary research, especially in the fields of polymer chemistry and material science, with a focus on their use in drug delivery applications [...].

Water-borne synthesis of multi-responsive and biodegradable chitosan-crosslinked microgels: Towards self-assembled films with adaptable properties.

The present study aims in the synthesis of new biodegradable stimuli-responsive microgels with controllable microstructure and with the ability to form cohesive films. Such self-assembled films by water evaporation at ambient conditions without any chemicals but just physical entanglements between soft colloid shell, present adaptable mechanical, adhesive and mechano-electrical properties. For that, oligo(ethylene glycol)-based stimuli-responsive microgels have been synthesized using biodegradable chitosan-methacrylates (Chi-MAs) with different degree of substitution (DS) as unique cross-linking agents by precipitation polymerization in water, for the first time. In all the cases, the microgels present thermo-responsiveness with hysteresis between heating and cooling cycles. However, this behavior is tuned and controlled using different types and amounts of Chi-MAs. In addition, the type of Chi-MA used can control microgels' microstructure as well as their enzymatic biodegradation. In addition, spontaneous cohesive films formation from colloidal aqueous dispersion with sol-gel transition is demonstrated. The films present tunable mechanical and adhesive properties through microgels' microstructure and enhanced mechano-electrical properties triggered by simple finger pressure (10-15 N). As self-supported films are able to encapsulate different types of active molecules, this study paves the way for suitable self-assembled microgel films for skincare applications as transdermal delivery systems.

Soft Self-Assembled Mechanoelectrical Transducer Films from Conductive Microgel Waterborne Dispersions.

The present study aims in the developing of new soft transducers based on sophisticated stimuli-responsive microgels that exhibit spontaneous self-assembly forming cohesive films with conductive and mechanoelectrical properties. For that, oligo(ethylene glycol)-based stimuli-responsive microgels have been synthesized using bio-inspired catechol cross-linkers by one-step batch precipitation polymerization in aqueous media. Then, 3,4-ethylene dioxyyhiophene (EDOT) has been directly polymerized onto stimuli-responsive microgels using catechol groups as the unique dopant. PEDOT location is dependent on the cross-linking density of microgel particles and EDOT amount used. Moreover, the spontaneous cohesive film formation ability of the waterborne dispersion after evaporation at soft application temperature is demonstrated. The films obtained present conductivity and enhanced mechanoelectrical properties triggered by simple finger compression. Both properties are function of the cross-linking density of the microgel seed particles and PEDOT amount incorporated. In addition, to obtain maximum electrical potential generated and the possibility to amplify it, several films in series were demonstrated to be efficient. The present material can be a potential candidate for biomedical, cosmetic, and bioelectronic applications.

Spontaneously Self-Assembled Microgel Film as Co-Delivery System for Skincare Applications.

Nowadays, the design of innovative delivery systems is driving new product developments in the field of skincare. In this regard, serving as potential candidates for on-demand drug delivery and fulfilling advanced mechanical and optical properties together with surface protection, spontaneously self-assembled microgel films can be proposed as ideal smart skincare systems. Currently, the high encapsulation of more than one drug simultaneously in a film is a very challenging task. Herein, different ratios (1:1, 3:1, 9:1) of different mixtures of hydrophilic/hydrophobic UVA/UVB-absorbers working together in synergy and used for skin protection were encapsulated efficiently into spontaneously self-assembled microgel films. In addition, in vitro release profiles show a controlled release of the different active molecules regulated by the pH and temperature of the medium. The analysis of the release mechanisms by the Peppas-Sahlin model indicated a superposition of diffusion-controlled and swelling-controlled releases. Finally, the distribution of active molecule mixtures into the film was studied by confocal Raman microscopy imaging corroborating the release profiles obtained.

Microgels self-assembly at liquid/liquid interface as stabilizers of emulsion: Past, present & future.

The most recent developments on Pickering emulsions deal with the design of responsive emulsions able to undergo fast destabilization under the effect of an external stimulus. In this scenario, soft colloidal particles like microgels are considered novel class suitable emulsifiers. Microgels particles self-assemblies are highly deformable at interfaces covering higher surfaces than hard particles and their interfacial behavior strongly depends on external-stimuli. Microgels are very diverse owing to the large variety of them from the point of view of possible combinations of stimuli-responsiveness and different microstructures (crosslinking density and distribution). Herein, we illustrate the use of different types of responsive microgels not only from a structural point of view but also even from physical one. For that, the effect of different microgels parameters such as internal structure and charge density on mechanical properties of the interface will be discussed.

Microstructure-driven self-assembly and rheological properties of multi-responsive soft microgel suspensions.

HYPOTHESES: The deformation and swelling ability of microgels is influenced by the crosslinking distribution. Varying microgels microstructure is expected to obtain suspensions with different flow behavior and thereby, different rheological properties. EXPERIMENTS: Different multi-responsive microgels were synthesized using two different crosslinkers and varying their amounts: N,N-methylene bis-acrylamide (MBA) and oligo(ethylene glycol) diacrylate (OEGDA). The rheological results were obtained by zero-shear viscosity and long-time creep measurements on concentrated microgel suspensions Microgel microstructure was analyzed by 1H nuclear magnetic resonance transverse relaxation measurements. FINDINGS: At a constant crosslinking rate, we show that the viscosity of OEGDA-crosslinked microgels diverges at a higher concentration than MBA ones, suggesting a looser shell and less restricted dangling chains at the periphery for the later. By scaling with the effective volume fraction, the viscosity curves of the different microgel suspensions reduce into a single curve and closely follow hard sphere models up to ϕeff < 0.45. The results from creep tests revealed a much higher yield stress for MBA-crosslinked microgels, strengthening the hypothesis of a looser shell for the later. Finally, transverse relaxation (T2) NMR measurements demonstrated that, although all microgels exhibit a core-shell microstructure, MBA samples present a less crosslinked shell corroborating with the rheological results.

Versatile oligo(ethylene glycol)-based biocompatible microgels for loading/release of active bio(macro)molecules.

The present study aims in the understanding of the effect of oligo(ethylene glycol)-based biocompatible microgels inner structure on the encapsulation/release mechanisms of different types of cosmetic active molecules. For that, multi-responsive microgels were synthesized using three types of cross-linkers: ethylene glycol dimethacrylate (EGDMA), oligo(ethylene glycol) diacrylate (OEGDA) and N,N-methylenebisacrylamide (MBA). The inner morphology of the microgels synthesized was studied by 1H-nuclear magnetic resonance (1H NMR) and small-angle neutron scattering (SANS) techniques and no effect of cross-linker type on microgel microstructure was observed in the case of analysing purified microgel dispersions. Moreover, all the microgels synthesized presented conventional swelling/de-swelling behavior as a function of temperature and pH. Two hydrophobic, one hydrophilic, and one macromolecule as cosmetic active molecules were effectively loaded into different microgel particles via hydrophobic interactions and hydrogen-bonding interactions between -OH groups of active molecules and ether oxygens of different microgel particles. Their release profiles as a function of cross-linker type used and encapsulated amounts were studied by Peppas-Sahlin model. No effect of the cross-linker type was observed due to the similar inner structure of all the microgels synthesized.