Novel polymers for biomedical and pharmaceutical applications: synthesis and characterization

The aim of this PhD thesis work has been the synthesis of novel antimicrobial amphiphilic polymers to prevent microbial biofilm related-infections and counteract microbial resistance onset. In fact, microbial biofilms are difficultly eradicable due to their high antibiotic resistance. To reach this purpose different strategies along this work were exploited

Novel polymers for biomedical and pharmaceutical applications: synthesis and characterization

The aim of this PhD thesis work has been the synthesis of novel antimicrobial amphiphilic polymers to prevent microbial biofilm related-infections and counteract microbial resistance onset. In fact, microbial biofilms are difficultly eradicable due to their high antibiotic resistance. To reach this purpose different strategies along this work were exploited

Poly (glycerol adipate) (PGA), an enzymatically synthesized functionalizable polyester and versatile drug delivery carrier : A literature update

The enzymatically synthesized poly (glycerol adipate) (PGA) has demonstrated all the desirable key properties required from a performing biomaterial to be considered a versatile "polymeric-tool" in the broad field of drug delivery. The step-growth polymerization pathway catalyzed by lipase generates a highly functionalizable platform while avoiding tedious steps of protection and deprotection. Synthesis requires only minor purification steps and uses cheap and readily available reagents. The final polymeric material is biodegradable, biocompatible and intrinsically amphiphilic, with a good propensity to self-assemble into nanoparticles (NPs). The free hydroxyl group lends itself to a variety of chemical derivatizations via simple reaction pathways which alter its physico-chemical properties with a possibility to generate an endless number of possible active macromolecules. The present work aims to summarize the available literature about PGA synthesis, architecture alterations, chemical modifications and its application in drug and gene delivery as a versatile carrier. Following on from this, the evolution of the concept of enzymatically-degradable PGA-drug conjugation has been explored, reporting recent examples in the literature.Peer reviewedFinal Published versio

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

Colorimetric transition of polydiacetylene/cyclodextrin supramolecular assemblies and implications as colorimetric sensors for food phenolic antioxidants

Molecular self-assembly has significant potential in the field of sensing. Polydiacetylenes (PDAs) are conjugated polymers possessing peculiar optical properties obtained by photopolymerization of self-assembled diacetylene monomers. Herein, the blue-to-red phase transition upon either thermal stimulus or interaction with cyclodextrins (CDs) of two PDAs, bearing either carboxylic (PCDA) or amino (PCDA-NH2) polar heads, is investigated to develop a colorimetric sensor for food phenolic antioxidants. The change in the PDA polar head does not affect significantly thermo-chromatic transition. Upon thermal stimulus, in both PDAs, color transition occurs straightforward between two distinct stable states and does not involve the disordering of the PDA crystal phase, as revealed by UV-vis spectroscopy and SAXS analysis. Contrarily, PDA/alpha-CD interaction is influenced by intermolecular forces among PDA polar heads and is more efficient for PCDA. alpha-CDs presumably cause changes in both PDA backbone conformation and local environment surrounding the individual PDA chains. The PCDA/alpha-CD assemblies are investigated as colorimetric sensors for the detection of Tyrosol (Ty) and caffeic acid (CAF), by using the principle of competitive inclusion complex formation. The system results to be more sensitive to CAF than Ty and may permit the determination of CAF in concentration ranges suitable for different food products

Polyglycerol Adipate-Grafted Polycaprolactone Nanoparticles as Carriers for the Antimicrobial Compound Usnic Acid

Nanoparticle (NP) drug delivery systems are known to potentially enhance the efficacy of therapeutic agents. As for antimicrobial drugs, therapeutic solutions against drug-resistant microbes are urgently needed due to the worldwide antimicrobial resistance issue. Usnic acid is a widely investigated antimicrobial agent suffering from poor water solubility. In this study, polymer nanoparticles based on polyglycerol adipate (PGA) grafted with polycaprolactone (PCL) were developed as carriers for usnic acid. We demonstrated the potential of the developed systems in ensuring prolonged bactericidal activity against a model bacterial species, Staphylococcus epidermidis. The macromolecular architecture changes produced by PCL grafted from PGA significantly influenced the drug release profile and mechanism. Specifically, by varying the length of PCL arms linked to the PGA backbone, it was possible to tune the drug release from a burst anomalous drug release (high PCL chain length) to a slow diffusion-controlled release (low PCL chain length). The developed nanosystems showed a prolonged antimicrobial activity (up to at least 7 days) which could be used in preventing/treating infections occurring at different body sites, including medical device-related infection and mucosal/skin surface, where Gram-positive bacteria are commonly involved

Rapid formulation of redox-responsive oligo-β-aminoester polyplexes with siRNA via jet printing

Here we describe a rapid inkjet formulation method for screening newly-synthesised cationic materials for siRNA delivery into cancer cells. Reduction responsive oligo-β-aminoesters were prepared and evaluated for their ability to condense siRNA into polyplexes through a fast inkjet printing method. A direct relationship between the oligomer structures and charge densities, and the final cell response in terms of uptake rate and transfection efficacy, was found. The oligo-β-aminoesters were well-tolerated by the cancer cells, compared to conventional cationic polymers so far employed in gene delivery, and were as active in silencing of a representative luciferase gene

Synthesis of two-phase polymer particles in supercritical carbon dioxide

The synthesis of particles with discrete phases using traditional emulsion polymerisation is a well-established process. Phase-separated particles have a wide range of applications, such as in coatings, drug delivery, impact modification and as supports in catalysis. However, as a dry powder is often desired for the end application, post-polymerisation, energy intensive drying steps are usually required for the removal of water. Alternatively, dispersion polymerisation utilising supercritical carbon dioxide (scCO2) as a reaction medium allows for the production of dry, free-flowing powders upon release of the CO2. Here, we present the innovative use of scCO2 to provide a novel and environmentally acceptable route for creating phase-separated particles. Particles containing a high Tg poly(methyl methacrylate) (PMMA) phase, combined with a low Tg polymer phase of either poly(benzyl acrylate) (PBzA) or poly(butyl acrylate) (PBA), were investigated. Both monomers were added to the reaction after the formation of PMMA seed particles. Benzyl acrylate (BzA) was chosen as a model low Tg monomer, with well-defined and detectable functionality when mixed with PMMA. Butyl acrylate (BA) was also used as an alternative, more industrially relevant monomer. The loading of the low Tg monomer was varied and full characterisation of the particles produced was performed to elucidate their internal morphologies and compositions