Intermolecular interaction and solid state characterization of abietic acid/chitosan solid dispersions possessing antimicrobial and antioxidant properties

The aim of this work was to prepare and characterize solid dispersions of abietic acid (AB) and chitosan (CS) to investigate how formulation of the mixture may help in the battle against microbial colonization in different areas, such as the biomedical field or the food industry. Solid dispersions were characterized by differential scanning calorimetry, infrared spectroscopy, Raman spectroscopy, polarized optical microscopy, zeta potential and size analysis. The data showed that the dispersion/solvent evaporation method formed solid dispersions in which abietic acid was molecularly dispersed in the carrier. A synergistic effect between the two components in terms of antioxidant and antimicrobial properties was found, especially in the formulations obtained with 1/1 AB/CS molar ratio. Interestingly, the aggregation state (amorphous/crystalline) of AB seemed to affect the antimicrobial activity of the formulation, suggesting increased bioactivity when the drug was in the amorphous state. These findings, together with the demonstrated biocompatibility of the formulations, seem to open promising perspectives for a successful application of the developed AB/CS formulations in the biomedical field or in the food industry

Co-delivery of curcumin and resveratrol by folic acid-conjugated poly(glycerol adipate) nanoparticles for enhanced synergistic anticancer effect against osteosarcoma

This study explored the co-delivery of curcumin (CUR) and resveratrol (RV) using folic acid-conjugated poly(glycerol adipate)-based nanoparticles (FPPC NPs) to enhance their synergistic anticancer effects against osteosarcoma. Based on synergistic toxicity experiments against Saos-2 cells, the optimal synergistic CUR:RV ratios were 1:2 and 1:3, which were used for co-encapsulation. Increasing the amount of RV in the co-loaded NPs did not affect the properties of the nanocarriers, but predominantly increased the loading capacity of RV, especially at the 1:3 ratio, by 1.8–2.0 times, mediated by their interaction. All co-loaded NPs demonstrated sustained release of CUR with a burst release of RV, and the presence of RV accelerated the initial release of CUR from the carriers. Furthermore, the co-encapsulated NPs maintained CUR and RV synergism and greatly enhanced their toxicity against osteosarcoma by at least 1.8 times compared to their corresponding solutions through profound accumulation of Saos-2 cells in the sub G1 phase and late apoptosis. The internalization of FPPC NPs into cells via endocytosis was dose- and time-dependent. This study offers a proof-of-concept for a potential co-delivery system using tumor-targeted poly(glycerol adipate)-based NPs to enhance the anticancer activity of CUR and RV against osteosarcoma

Comparative hydrodynamic characterisation of two hydroxylated polymers based on α-pinene- or oleic acid-derived monomers for potential use as archaeological consolidants

The Oseberg Viking ship burial is one of the most extensive collections of Viking wooden artefacts ever excavated in Norway. In the early twentieth century, many of these artefacts were treated with alum in order to preserve them, inadvertently leading to their current degraded state. It is therefore crucial to develop new bioinspired polymers which could be used to conserve these artefacts and prevent further disintegration. Two hydroxylated polymers were synthesised (TPA6 and TPA7), using α-pinene- and oleic acid-derived monomers functionalised with an acrylate moiety. Characterisation using biomolecular hydrodynamics (analytical ultracentrifugation and high precision viscometry) has shown that these polymers have properties which would potentially make them good wood consolidants. Conformation analyses with the viscosity increment (ν) universal hydrodynamic parameter and ELLIPS1 software showed that both polymers had extended conformations, facilitating in situ networking when applied to wood. SEDFIT-MSTAR analyses of sedimentation equilibrium data indicates a weight average molar mass Mw of (3.9 ± 0.8) kDa and (4.2 ± 0.2) kDa for TPA6 and TPA7 respectively. Analyses with SEDFIT (sedimentation velocity) and MultiSig however revealed that TPA7 had a much greater homogeneity and a lower proportion of aggregation. These studies suggest that both these polymers—particularly TPA7—have characteristics suitable for wood consolidation, such as an optimal molar mass, conformation and a hydroxylated nature, making them interesting leads for further research

A new particle mounting method for surface analysis

The chemical analysis of microparticles is challenging due to the need to mount the particles on a substrate for analysis; double sided adhesive tape is often used (sometimes conductive), however that is usually coated with poly(dimethyl siloxane) (PDMS) which is often used as a release agent. PDMS is a common surface contamination that can mask surface chemistries and hinder material performance where it is dependent on this contaminated interface. It is known that PDMS contains a very mobile oligomeric fraction that readily diffuses across surfaces resulting in the contamination of mounted particulate samples before and during surface chemistry analysis. This makes it impossible to determine whether the PDMS has arisen from the analysis procedure or from the sample itself. A new sample preparation method is proposed where polymer microparticles are mounted on a poly(hydroxyethyl methacrylate) (pHEMA) polymer solution, which we compare with particles that have been mounted on adhesive discs using time of flight secondary ion mass spectrometry (ToF-SIMS) and 3D OrbiSIMS analysis. Particles mounted on the pHEMA substrate results in a reduction of PDMS signal by 99.8% compared to microparticles mounted on adhesive discs. This illustrates how a simple, quick and inexpensive polymer solution can be used to adhere particles for analysis by ToF-SIMS, or other surface chemical analysis techniques such as XPS, without introduction of large amounts of silicone contaminant

Polymer microparticles with defined surface chemistry and topography mediate the formation of stem cell aggregates and cardiomyocyte function

Surface-functionalized microparticles are relevant to fields spanning engineering and biomedicine, with uses ranging from cell culture to advanced cell delivery. Varying topographies of biomaterial surfaces are also being investigated as mediators of cell-material interactions and subsequent cell fate. To investigate competing or synergistic effects of chemistry and topography in three-dimensional (3D) cell cultures, methods are required to introduce these onto microparticles without modification of their underlying mor-phology or bulk properties. In this study, a new approach for surface functionalization of poly(lactic acid) (PLA) microparticles is reported that allows decoration of the outer shell of the polyesters with additional polymers via aqueous atom transfer radical polymerization (ATRP) routes. PLA microparticles with smooth or dimpled surfaces were functionalized with poly(poly(ethylene glycol) methacrylate) (pPEG-MA) and poly[N-(3-aminopropyl)methacrylamide] (pAPMA) brushes, chosen for their potential abilities to mediate cell adhesion. X-ray Photoelectron Spectroscopy (XPS) and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis indicated homogeneous coverage of the microparticles with pol-ymer brushes while maintaining the original topographies. These materials were used to investigate the relative importance of surface chemistry and topography both on the formation of human immortalized mesenchymal stem cell (hiMSCs) particle-cell aggregates and on the enhanced contractility of cardiomyo-cytes derived from human induced pluripotent stem cells (hiPSC-CMs). The influence of surface chemis-try was found to be more important on the size of particle-cell aggregates than topographies. In addition, surface chemistries that best promoted hiMSC attachment also improved hiPSC-CM attachment and con-tractility. These studies demonstrated a new route to obtain topo-chemical combinations on polyester-based biomaterials, and provided clear evidence for the predominant effect of surface functionality over micron-scale dimpled topography in cell-microparticle interactions. These findings thus provide new guiding principles for the design of biomaterial interfaces to direct cell function

Achieving Microparticles with Cell-Instructive Surface Chemistry by Using Tunable Co-Polymer Surfactants

© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim A flow-focusing microfluidic device is used to produce functionalized monodisperse polymer particles with surface chemistries designed to control bacterial biofilm formation. This is achieved by using molecularly designed bespoke surfactants synthesized via catalytic chain transfer polymerization. This novel approach of using polymeric surfactants, often called surfmers, containing a biofunctional moiety contrasts with the more commonly employed emulsion methods. Typically, the surface chemistry of microparticles are dominated by unwanted surfactants that dilute/mask the desired surface response. Time of flight secondary ion mass spectrometry (ToF-SIMS) analysis of particles demonstrates that the comb-graft surfactant is located on the particle surface. Biofilm experiments show how specifically engineered surface chemistries, generated by the surfactants, successfully modulate bacterial attachment to both polymer films, and microparticles. Thus, this paper outlines how the use of designed polymeric surfactants and droplet microfluidics can exert control over both the surface chemistry and size distribution of microparticle materials, demonstrating their critical importance for controlling surface-cell response

Droplet Microfluidic Optimisation Using Micropipette Characterisation of Bio-Instructive Polymeric Surfactants

Droplet microfluidics can produce highly tailored microparticles whilst retaining monodispersity. However, these systems often require lengthy optimisation, commonly based on a trial-and-error approach, particularly when using bio-instructive, polymeric surfactants. Here, micropipette manipulation methods were used to optimise the concentration of bespoke polymeric surfactants to produce biodegradable (poly(d,l-lactic acid) (PDLLA)) microparticles with unique, bio-instructive surface chemistries. The effect of these three-dimensional surfactants on the interfacial tension of the system was analysed. It was determined that to provide adequate stabilisation, a low level (0.1% (w/v)) of poly(vinyl acetate-co-alcohol) (PVA) was required. Optimisation of the PVA concentration was informed by micropipette manipulation. As a result, successful, monodisperse particles were produced that maintained the desired bio-instructive surface chemistry

Discovery of (meth)acrylate polymers that resist colonization by fungi associated with pathogenesis and biodeterioration

© 2020 The Authors. Fungi have major, negative socioeconomic impacts, but control with bioactive agents is increasingly restricted, while resistance is growing. Here, we describe an alternative fungal control strategy via materials operating passively (i.e., no killing effect). We screened hundreds of (meth)acrylate polymers in high throughput, identifying several that reduce attachment of the human pathogen Candida albicans, the crop pathogen Botrytis cinerea, and other fungi. Specific polymer functional groups were associated with weak attachment. Low fungal colonization materials were not toxic, supporting their passive, anti-attachment utility. We developed a candidate monomer formulation for inkjet-based 3D printing. Printed voice prosthesis components showed up to 100% reduction in C. albicans biofilm versus commercial materials. Furthermore, spray-coated leaf surfaces resisted fungal infection, with no plant toxicity. This is the first high-throughput study of polymer chemistries resisting fungal attachment. These materials are ready for incorporation in products to counteract fungal deterioration of goods, food security, and health

Amphiphilic tri- and tetra-block co-polymers combining versatile functionality with facile assembly into cytocompatible nanoparticles

In order for synthetic polymers to find widespread practical application as biomaterials, their syntheses must be easy to perform, utilising freely available building blocks, and should generate products which have no adverse effects on cells or tissue. In addition, it is highly desirable that the synthesis platform for the biomaterials can be adapted to generate polymers with a range of physical properties and macromolecular architectures, and with multiple functional handles to allow derivatisation with 'actives' for sensing or therapy. Here we describe the syntheses of amphiphilic tri-and tetra-block copolymers, using diazabicyclo[5.4.0]undec-5-ene (DBU) as a metal-free catalyst for ring-opening polymerisations of the widely-utilised monomer lactide combined with a functionalised protected cyclic carbonate. These syntheses employed PEGylated macroinitiators with varying chain lengths and architectures, as well as a labile-ester methacrylate initiator, and produced block copolymers with good control over monomer incorporation, molar masses, side-chain and terminal functionality and physico-chemical properties. Regardless of the nature of the initiators, the fidelity of the hydroxyl end group was maintained as confirmed by a second ROP chain extension step, and polymers with acryloyl/methacryloyl termini were able to undergo a second tandem reaction step, in particular thiol-ene click and RAFT polymerisations for the production of hyperbranched materials. Furthermore, the polymer side-chain functionalities could be easily deprotected to yield an active amine which could be subsequently coupled to a drug molecule in good yields. The resultant amphiphilic copolymers formed a range of unimolecular or kinetically-trapped micellar-like nanoparticles in aqueous environments, and the non-cationic polymers were all well-tolerated by MCF-7 breast cancer cells. The rapid and facile route to such highly adaptable polymers, as demonstrated here, offers promise for a range of bio materials applications

Microparticles Decorated with Cell‐Instructive Surface Chemistries Actively Promote Wound Healing

Wound healing is a complex biological process involving close crosstalk between various cell types. Dysregulation in any of these processes, such as in diabetic wounds, results in chronic non-healing wounds. Fibroblasts are a critical cell type involved in the formation of granulation tissue, essential for effective wound healing. We screened 315 different polymer surfaces to identify candidates which actively drove fibroblasts towards either pro- or anti-proliferative functional phenotypes. Fibroblast-instructive chemistries were identified, which we synthesized into surfactants to fabricate easy to administer microparticles for direct application to diabetic wounds. The pro-proliferative microfluidic derived particles were able to successfully promote neovascularisation, granulation tissue formation and wound closure after a single application to the wound bed. These active novel 3D bio-instructive microparticles show great potential as a route to reducing the burden of chronic wounds