Nanotechnology-based techniques for hair follicle regeneration.

The hair follicle (HF) is a multicellular complex structure of the skin that contains a reservoir of multipotent stem cells. Traditional hair repair methods such as drug therapies, hair transplantation, and stem cell therapy have limitations. Advances in nanotechnology offer new approaches for HF regeneration, including controlled drug release and HF-specific targeting. Until recently, embryogenesis was thought to be the only mechanism for forming hair follicles. However, in recent years, the phenomenon of wound-induced hair neogenesis (WIHN) or de novo HF regeneration has gained attention as it can occur under certain conditions in wound beds. This review covers HF-specific targeting strategies, with particular emphasis on currently used nanotechnology-based strategies for both hair loss-related diseases and HF regeneration. HF regeneration is discussed in several modalities: modulation of the hair cycle, stimulation of progenitor cells and signaling pathways, tissue engineering, WIHN, and gene therapy. The HF has been identified as an ideal target for nanotechnology-based strategies for hair regeneration. However, some regulatory challenges may delay the development of HF regeneration nanotechnology based-strategies, which will be lastly discussed.

Targeted downregulation of MYC mediated by a highly efficient lactobionic acid-based glycoplex to enhance chemosensitivity in human hepatocellular carcinoma cells.

The chemosensitization of tumor cells by gene therapy represents a promising strategy for hepatocellular carcinoma (HCC) treatment. In this regard, HCC-specific and highly efficient gene delivery nanocarriers are urgently needed. For this purpose, novel lactobionic acid-based gene delivery nanosystems were developed to downregulate c-MYC expression and sensitize tumor cells to low concentration of sorafenib (SF). A library of tailor-made cationic glycopolymers, based on poly(2-aminoethyl methacrylate hydrochloride) (PAMA) and poly(2-lactobionamidoethyl methacrylate) (PLAMA) were synthesized by a straightforward activators regenerated by electron transfer atom transfer radical polymerization. The nanocarriers prepared with PAMA114-co-PLAMA20 glycopolymer were the most efficient for gene delivery. These glycoplexes specifically bound to the asialoglycoprotein receptor and were internalized through the clathrin-coated pit endocytic pathway. c-MYC expression was significantly downregulated by MYC short-hairpin RNA (MYC shRNA), resulting in efficient inhibition of tumor cells proliferation and a high levels apoptosis in 2D and 3D HCC-tumor models. Moreover, c-MYC silencing increased the sensitivity of HCC cells to SF (IC50 for MYC shRNA + SF 1.9 µM compared to 6.9 µM for control shRNA + SF). Overall, the data obtained demonstrated the great potential of PAMA114-co-PLAMA20/MYC shRNA nanosystems combined with low doses of SF for the treatment of HCC.

Glycopolymers Mediate Suicide Gene Therapy in ASGPR-Expressing Hepatocellular Carcinoma Cells in Tandem with Docetaxel.

Cationic glycopolymers stand out as gene delivery nanosystems due to their inherent biocompatibility and high binding affinity to the asialoglycoprotein receptor (ASGPR), a target receptor overexpressed in hepatocellular carcinoma (HCC) cells. However, their synthesis procedure remains laborious and complex, with problems of solubilization and the need for protection/deprotection steps. Here, a mini-library of well-defined poly(2-aminoethyl methacrylate hydrochloride-co-poly(2-lactobionamidoethyl methacrylate) (PAMA-co-PLAMA) glycopolymers was synthesized by activators regenerated by electron transfer (ARGET) ATRP to develop an efficient gene delivery nanosystem. The glycoplexes generated had suitable physicochemical properties and showed high ASGPR specificity and high transfection efficiency. Moreover, the HSV-TK/GCV suicide gene therapy strategy, mediated by PAMA144-co-PLAMA19-based nanocarriers, resulted in high antitumor activity in 2D and 3D culture models of HCC, which was significantly enhanced by the combination with small amounts of docetaxel. Overall, our results demonstrated the potential of primary-amine polymethacrylate-containing-glycopolymers as HCC-targeted suicide gene delivery nanosystems and highlight the importance of combined strategies for HCC treatment.

pH-responsive nanoparticles based on POEOMA-b-PDPA block copolymers for RNA encapsulation, protection and cell delivery.

The use of gene-based products, such as DNA or RNA, is increasingly being explored for various innovative therapies. However, the success of these strategies is highly dependent on the effective delivery of these biomolecules to target cells. Therefore, the development of pH-responsive nanoparticles comprises the creation of intelligent delivery systems with high therapeutic efficiency. In this work, the pH-responsiveness of the poly(2-(diisopropylamino)ethyl methacrylate)) (PDPA) block was investigated for the encapsulation and delivery of small RNAs (sRNA) to cancer cells. The pH responsiveness was dependent on the protonation profile of the tertiary amines of PDPA, which directly affected the electrostatic interactions established with RNA. Thus, block copolymers based on poly(oligo(ethylene oxide) methyl ether methacrylate) (POEOMA) and PDPA, POEOMA-b-PDPA, were synthesized by supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP). The structure of the block copolymers was characterized by size exclusion chromatography and 1H NMR spectroscopy. The copolymers allowed effective complexation of model sRNAs and a pre-miRNA with efficiencies of about 89 % and 91 %, respectively. The characterization by dynamic light scattering revealed that these systems had sizes between 76 and 1375 nm. It was also found that the morphology of the polyplexes depended on the pH, since the preparation at a pH lower than the pKa of the copolymers resulted in spherical but polydisperse particles, while higher pH values resulted in nanoparticles with more homogeneous size, but altered morphology. Moreover, due to pH-responsiveness, it was achieved the release of RNA at pH higher than the pKa of the copolymers, while maintaining its integrity. The polyplexes also showed a high potential to protect RNA from RNases. The transfection of a lung cancer model (A549) and fibroblast cell lines showed that these polyplexes did not cause cell toxicity. In addition, the polyplexes enabled the effective transfection of the A549 cell line with pre-miRNA-29b and miRNA-29b, resulting in a decrease of expression levels of the target DNMT3B gene by approximately 51 % and 47 %, respectively. Overall, the POEOMA-b-PDPA copolymers proved to be a promising strategy for developing responsive delivery systems, that can play a critical role in some diseases, such as cancer, where pH varies between the intra and extracellular environments.

Application of vinyl polymer-based materials as nucleic acids carriers in cancer therapy.

Nucleic acid-based therapies have changed the paradigm of cancer treatment, where conventional treatment modalities still have several limitations in terms of efficacy and severe side effects. However, these biomolecules have a short half-life in vivo, requiring multiple administrations, resulting in severe suffering, discomfort, and poor patient compliance. In the early days of (nano)biotechnology, these problems caused concern in the medical community, but recently it has been recognized that these challenges can be overcome by developing innovative formulations. This review focuses on the use of vinyl polymer-based materials for the protection and delivery of nucleic acids in cancer. First, an overview of the properties of nucleic acids and their versatility as drugs is provided. Then, key information on the achievements to date, the most effective delivery methods, and the evaluation of functionalization approaches (stimulatory strategies) are critically discussed to highlight the importance of vinyl polymers in the new cancer treatment approaches. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures.

Light-Activated Antimicrobial Surfaces Using Industrial Varnish Formulations to Mitigate the Incidence of Nosocomial Infections.

Evidence has shown that hospital surfaces are one of the major vehicles of nosocomial infections caused by drug-resistant pathogens. Smart surface coatings presenting multiple antimicrobial activity mechanisms have emerged as an advanced approach to safely prevent this type of infection. In this work, industrial waterborne polyurethane varnish formulations containing for the first time cationic polymeric biocides (SPBs) combined with photosensitizer curcumin were developed to afford contact-active and light-responsive antimicrobial surfaces. SPBs were prepared by atom transfer radical polymerization, which allows control over the polymer features that influence antimicrobial efficiency (e.g., molecular weight), while natural curcumin was employed to impart photodynamic activity to the surface. Antibacterial testing against Gram-negative Escherichia coli revealed that glass surfaces coated with the new formulations displayed photokilling effect under white-light (42 mW/cm2) irradiation within only 15 min of exposure. In addition, it was observed a combined antimicrobial effect between the two biocides (cationic SPB and curcumin), with a higher reduction in the number of viable bacteria observed for the surfaces containing cationic SPB/curcumin mixtures in comparison with the one obtained for surfaces only with polymer or without biocides. The waterborne industrial varnish formulations allowed the formation of homogeneous films without the need for addition of a coalescing agent, which can be potentially applied in diverse surface substrates to reduce bacterial transmission infections in healthcare environments.

The Impact of the Addition of Compatibilizers on Poly (lactic acid) (PLA) Properties after Extrusion Process.

Poly (lactic acid) (PLA), due to its biodegradability, biocompatibility, and renewability, is one of the most promising biobased polymers for replacing some of the petrol-based materials. Low flexibility of PLA is overcome, by blending it with olefin-based polymers, such as polypropylene (PP). However, the use of compatibilizing agents is required to attain final materials with suitable mechanical properties. Such agents, although essential, can affect PLA structure and, consequently, the mechanical properties of the PLA. To the best of our knowledge, this issue was never studied, and the results can contribute to achieving the best formulations of PLA-based blends according to their final applications. The thermal and mechanical properties of the extruded PLA, with three different commercial compatibilizing agents, were evaluated with the purpose of demonstrating how the compatibilizers can introduce structural differences into the PLA chain during the extrusion process. The combination of crystallinity, molecular weight, and the morphology of the samples after extrusion determines the final mechanical properties of PLA. Despite being a fundamental study, it is our aim to contribute to the sustainability of PLA-based industries. The addition of a 2.5% concentration of C1 compatibilizer seems to have less influence on the final morphology and mechanical properties of the blends.

Development of red-light cleavable PEG-PLA nanoparticles as delivery systems for cancer therapy.

The development of targeted delivery systems can improve the selectivity of cancer drugs. Additionally, a system that promotes the controlled delivery of the drug triggered by an external stimulus in the exact target tissue is highly desirable. Regarding the light stimulus, the NIR window (650-950 nm) is the most suitable due to its higher capacity of penetration in human tissues and less harmful effects on normal cells. In this work, new red-light-responsive nanoparticles for doxorubicin delivery were developed. The nanoparticles were based on cleavable di-block copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid) (PLA) linked by a red-light sensitive segment (1,2-bis(2-hydroxyethylthio)ethylene, BHETE). The PEG-BHETE-PLA copolymers were synthesized under mild conditions and exhibited a narrow polydispersity. The nanoparticles presented a size between 53 and 133 nm, with a doxorubicin loading capacity between 1.2 and 4.4 wt%. Release study of the encapsulated doxorubicin confirms the light-triggered nanoparticle disassembly process. In vitro cytotoxicity tests in MCF7 cell line, for the light-triggered nanoparticles, showed a decrease in cancer cells' viability higher than 25% compared to non-irradiated cells. Due to the promising results obtained with the light-sensitive PEG-BHETE-PLA nanoparticles, these materials have great potential to be used in drug delivery systems for cancer therapy.

Use of recycled polypropylene/poly(ethylene terephthalate) blends to manufacture water pipes: An industrial scale study.

Poly(ethylene terephthalate) (PET) and polypropylene (PP) are two major polymeric materials that constitute many single-use plastic products. A common strategy to reduce polymeric waste is via mechanical recycling, a low cost and efficient process. However, from an industrial point of view, the reliability of this process is more easily achieved by a downgrade in the final properties of these materials, which limits the usage of recycled-based materials to less demanding applications. Furthermore, due to the intrinsic heterogeneity of the PP or PET waste, the use of these materials in industrial processing, tuned and developed for virgin neat materials, poses serious integrity problems. This aspect is particularly relevant in the case of plastics originating from the food packaging industry. This work explores the possibility of incorporating either PP or PET originated from plastic solid waste (PSW), in pipe manufacturing, with competitive mechanical properties compared to those prepared from virgin materials. To achieve this industrial solution, a process was developed using PP/PET 70/30 wt% formulations and the impact of replacing the virgin material by the different PSW in the microstructure, thermal and mechanical properties of the final material was analyzed. The impact of using a compatibilizer able to counteract the natural immiscibility between the PP and PET domains was also assessed. The developed formulation with recycled PET is a good example of the applicability of work developed at a laboratory scale into industrial-scale production.

Poly(ß-amino ester)-based gene delivery systems: From discovery to therapeutic applications.

Poly(ß-amino ester)s (PßAE) were firstly synthesized in 1983 but only in 2000 these polymers were used for the first time as gene carrier. Thenceforward, due to their excellent gene delivery properties, PßAE were amply explored to afford very effective non-viral vectors. The promising results obtained both in vitro and in vivo studies involving different areas, from cancer therapy to tissue engineering area have aroused a broad interest of the scientific community for this family of biodegradable cationic polymers. This review is the first comprehensive and critical overview of the use of PßAEs as gene carrier. The rational design of PßAEs is a major step aiming to achieve high transfection efficiencies. Moreover, it has been demonstrated that often very small changes in the structure of these polymers have an impressive impact on the transfection efficiency. A critical discussion on the structure performance relationships is presented as well as the outlook for next developments involving these polymers.

Poly(ethylene glycol)- block-poly(2-aminoethyl methacrylate hydrochloride)-Based Polyplexes as Serum-Tolerant Nanosystems for Enhanced Gene Delivery.

Incorporation of poly(ethylene glycol) (PEG) into polyplexes has been used as a promising approach to enhance their stability and reduce unwanted interactions with biomolecules. However, this strategy generally has a negative influence on cellular uptake and, consequently, on transfection of target cells. In this work, we explore the effect of PEGylation on biological and physicochemical properties of poly(2-aminoethyl methacrylate) (PAMA)-based polyplexes. For this purpose, different tailor-made PEG- b-PAMA block copolymers, and the respective homopolymers, were synthesized using the controlled/"living" radical polymerization method based on activators regenerated by electron transfer atom transfer radical polymerization. The obtained data show that PEG- b-PAMA-based polyplexes exhibited a much better transfection activity/cytotoxicity relationship than the corresponding non-PEGylated nanocarriers. The best formulation, prepared with the largest block copolymer (PEG45- b-PAMA168) at a 25:1 N/P ratio, presented a 350-fold higher transfection activity in the presence of serum than that obtained with polyplexes generated with the gold standard bPEI. This higher transfection activity was associated to an improved capability to overcome the intracellular barriers, namely the release from the endolysosomal pathway and the vector unpacking and consequent DNA release from the nanosystem inside cells. Moreover, these nanocarriers exhibit suitable physicochemical properties for gene delivery, namely reduced sizes, high DNA protection, and colloidal stability. Overall, these findings demonstrate the high potential of the PEG45- b-PAMA168 block copolymer as a gene delivery system.

The influence of poly(ester amide) on the structural and functional features of 3D additive manufactured poly(ε-caprolactone) scaffolds.

The current research reports for the first time the use of blends of poly(ε-caprolactone) (PCL) and poly(ester amide) (PEA) for the fabrication of 3D additive manufactured scaffolds. Tailor made PEA was synthesized to afford fully miscible blends of PCL and PEA using different percentages (5, 10, 15 and 20% w/w). Stability, characteristic temperatures and material's compatibility were studied through thermal analyses (i.e., TGA, DSC). Even though DMTA and static compression tests demonstrated the possibility to improve the storage modulus, Young's modulus and maximum stress by increasing the amount of PEA, a decrease of hardness was found beyond a threshold concentration of PEA as the lowest values were achieved for PCL/PEA (20% w/w) scaffolds (from 0.39 ±â€¯0.03 GPa to 0.21 ±â€¯0.02 GPa in the analysed load range). The scaffolds presented a controlled morphology and a fully interconnected network of internal channels. The water contact angle measurements showed a clear increase of hydrophilicity resulting from the addition of PEA. This result was further corroborated with the improved adhesion and proliferation of human mesenchymal stem cells (hMSCs). The presence of PEA also influenced the cell morphology. Better cell spreading and a much higher and homogenous number of cells were observed for PCL/PEA scaffolds when compared to PCL ones.

Near infrared light-triggered nanoparticles using singlet oxygen photocleavage for drug delivery systems.

Drug delivery systems (DDSs) have showed a reduced systemic toxicity and enhanced therapeutic efficacy over conventional cancer treatments. However, after reaching the damaged tissue, DDSs should present a trigger release of the encaged therapeutics. Among all methodologies for a controlled release system, the use of light in NIR window (650-900 nm) shows the most appropriate characteristics for biological applications (e.g. biocompatibility with tissues). This review is focused on NIR responsive approaches for DDSs intermediated by a photosensitizer (PS) using nanoparticles (NP) that possess oxidation sensitive segments. After excited by light, the PS generates singlet oxygen species which interact with a sensitive segment, causing bond cleavage or hydrophobicity change in NP followed by the release of entrapped therapeutics. The most relevant sensitive segments addressed in this work are: olefin (lipid, vinyl ether, vinyl disulfide, and aminoacrylate), thioketal, selenium and hydrophobicity changeable polymers (tellurium, poly(propylene sulfide), imidazole and nitroimidazole). The chemical structure of the sensitive segment, the available strategies for nanoparticle formation and DDSs in vitro and in vivo studies are also critically discussed. These NIR responsive DDSs have enormous potential as a tool for a controlled spatial-temporal drug release with capacity to overcome the drawbacks of the others specificity target DDSs (such as pH, temperature and ROS). In order to reach the pharmacological market, the light sensibility of the labile segments should increase for the range of wavelengths used and more biological test should be addressed.

Preparation of well-defined brush-like block copolymers for gene delivery applications under biorelevant reaction conditions.

Well-defined oligo(ethylene glycol) methyl ether methacrylate (OEOMA) based block copolymers with cationic segments composed by N,N-(dimethylamino) ethyl methacrylate (DMAEMA) and/or 2-(diisopropylamino) ethyl methacrylate (DPA) were developed under biorelevant reaction conditions. These brush-type copolymers were synthesized through supplemental activator and reducing agent (SARA) atom transfer radical polymerization (ATRP) using sodium dithionite as SARA agent. The synthesis was carried out using an eco-friendly solvent mixture, very low copper catalyst concentration, and mild reaction conditions. The structure of the block copolymers was characterized by size exclusion chromatography (SEC) analysis and 1H nuclear magnetic resonance (NMR) spectroscopy. The pH-dependent protonation of these copolymers enables the efficient complexation with plasmid DNA (pDNA), yielding polyplexes with sizes ranging from 200 up to 700 nm, depending on the molecular weight of the copolymers, composition and concentration used. Agarose gel electrophoresis confirmed the successful pDNA encapsulation. No cytotoxicity effect was observed, even for N/P ratios higher than 50, for human fibroblasts and cervical cancer cell lines cells. The in vitro cellular uptake experiments demonstrated that the pDNA-loaded block copolymers were efficiently delivered into nucleus of cervical cancer cells. The polymerization approach, the unique structure of the block copolymers and the efficient DNA encapsulation presented can open new avenues for development of efficient tailor made gene delivery systems under biorelevant conditions.

Combination of Poly[(2-dimethylamino)ethyl methacrylate] and Poly(ß-amino ester) Results in a Strong and Synergistic Transfection Activity.

This work reports an innovative and very effective gene delivery nanosystem, based on the combination of poly[(2-dimethylamino)ethyl methacrylate] (PDMAEMA) and poly(ß-amino ester) (PßAE) homopolymers, that has the capacity to efficiently deliver genetic material into target cells, even in the presence of serum. The best formulation, prepared with the combination PDMAEMA/4PßAE at the 25/1 nitrogen/phosphate (N/P) ratio, presented a 700-fold and 220-fold higher transfection activity than that obtained with branched polyethylenimine (PEI)-based polyplexes and block copolymer-based polyplexes, respectively. This new nanocarrier revealed high transgene expression in different human cells, including hard-to-transfect normal human astrocytes. The polyplexes presented high protection of genetic material and reduced sizes, which are suitable physicochemical properties for in vivo applications. Overall, this study demonstrates that the combination of PDMAEMA and PßAE homopolymers resulted in a noticeable and synergistic effect in terms of transfection activity, without causing substantial toxicity, constituting a new platform for the development of gene delivery nanosystems.

High transfection efficiency promoted by tailor-made cationic tri-block copolymer-based nanoparticles.

Cationic polymer-based vectors have been considered a promising strategy in gene therapy area due to their inherent ability to condense genetic material and successfully transfect cells. However, they usually exhibit high cytotoxicity. In this work, it is proposed the use of a tailor-made gene carrier based on a tri-block copolymer of poly[2-(dimethylamino)ethyl methacrylate] and poly(ß-amino ester) (PDMAEMA-b-PßAE-b-PDMAEMA), the influence of the PßAE length being assessed. For this purpose, three different block copolymers were prepared varying the molecular weight of this segment. The obtained materials were characterized by NMR and SEC analyzes. Different polyplexes formulations were prepared and evaluated in terms of physicochemical characterization (ethidium bromide intercalation assay, agarose gel electrophoresis assay, dynamic light scattering, zeta potential analyzes and atomic force microscopy) and biological activity (cytotoxicity, and luciferase and green fluorescent protein expression in Hela and COS-7 cell lines). Among the developed nanosystems, the best polyplex formulation revealed between 40- and 60-fold higher transgene expression, in HeLa and COS-7 cell lines, and much lower cytotoxicity than that observed with branched PEI and TurboFect™. Moreover, these nanosystems present suitable physicochemical properties for gene delivery namely reduced mean diameter and high DNA protection. The results reported here show the enormous potential of this block copolymer as gene carrier. STATEMENT OF SIGNIFICANCE: Syntheses of PDMAEMA-b-PßAE-b-PDMAEMA block copolymers for an extremely effective non-viral vector. The block copolymer PDMAEMA3000-b-PßAE12000-b-PDMAEMA3000-based polyplexes at 100/1N/P ratio exhibits between 40- and 60-fold higher transgene expression in HeLa and COS-7 cell lines than commonly used polymeric non-viral vectors, namely branched PEI (known as the gold standard) and TurboFect™ (commercial available).

Room temperature aqueous self-assembly of poly(ethylene glycol)-poly(4-vinyl pyridine) block copolymers: From spherical to worm-like micelles.

The solution self-assembly and the formation, at room temperature, of a wide range of nanostructures based on monomethyl ether poly(ethylene glycol)-b-poly(4-vinyl pyridine) (mPEG-b-P4VP) block copolymer is reported. Copolymers with different compositions and molecular weights were synthesized through Atom Transfer Radical Polymerization (ATRP) method. The solution self-assembly of the block copolymers was studied by transmission electron microscopy (TEM) for different solution pHs. It was found that the formation of non-spherical nanostructures, such as rod- and worm-like micelles can be easily achieved, at room temperature, by simply varying the molecular weight of the different segments as well as the mPEG to P4VP ratio in the block copolymer structure. Because P4VP segments are known to form strong complexes with metals, the nanostructures prepared in this manuscript can find innovative applications in the biomedical field and be used as nano-templates for inorganic materials.

Bioabsorbable polymers in cancer therapy: latest developments.

Cancer is a devastating disease, being responsible for 13 % of all deaths worldwide. One of the main challenges in treating cancer concerns the fact that anti-cancer drugs are not highly specific for the cancer cells and the "death" of healthy cells in the course of chemotherapy treatment is inevitable. In this sense, the use of drug delivery systems (DDS) can be seen as a powerful tool to minimize or overcome this very important issue. DDS can be designed to target specific tissues in order to mitigate side effects. Bioabsorbable polymers, due to their inherent characteristics, and because they can be synthesized in a variety of forms, are materials whose importance in the DDS for cancer therapy has risen significantly in the last years. This review intends to give an overview about the latest developments in the use of bioabsorbable polymers as DDS in cancer therapy, with special focus on nanoparticles, micelles, and implants.

Novel cationic triblock copolymer of poly[2-(dimethylamino)ethyl methacrylate]-block-poly(ß-amino ester)-block-poly[2-(dimethylamino)ethyl methacrylate]: a promising non-viral gene delivery system.

This manuscript reports the synthesis of a new cationic block copolymer based on poly[2-(dimethylamino)ethyl methacrylate] and poly(ß-amino ester) from different polymerization strategies. For the first time, it is proposed a triblock copolymer based only on cationic segments, aiming a high biocompatibility, enhanced buffering capacity and stimuli-responsive character in a single structure. The new block copolymer successfully condensed the plasmid DNA into nanosized polyplexes. The polyplexes were tested in two different cell lines revealing ∼4-fold and ∼6-fold (in HeLa cells), and ∼11-fold (in COS-7 cells) higher transgene expression than branched PEI and TurboFect™, respectively. These results show that this new block copolymer is a promising candidate to be used as a polymeric non-viral vector.

Phosphonium-based ionic liquids as modifiers for biomedical grade poly(vinyl chloride).

This work reports and discusses the influence of four phosphonium-based ionic liquids (PhILs), namely trihexyl(tetradecyl) phosphonium dicyanamide, [P(6,6,6,14)][dca]; trihexyl(tetradecyl) phosphonium bis(trifluoromethylsulfonyl)imide, [P(6,6,6,14)][Tf(2)N]; tetrabutyl phosphonium bromide, [P(4,4,4,4)][Br]; and tetrabutyl phosphonium chloride, [P(4,4,4,4)][Cl], on some of the chemical, physical and biological properties of a biomedical-grade suspension of poly(vinyl chloride) (PVC). The main goal of this work was to evaluate the capacity of these PhILs to modify some of the properties of neat PVC, in particular those that may allow their use as potential alternatives to traditional phthalate-based plasticizers in PVC biomedical applications. PVC films having different PhIL compositions (0, 5, 10 and 20 wt.%) were prepared (by solvent film casting) and characterised by Fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, dynamical mechanical thermal analysis, scanning electron microscopy/energy-dispersive X-ray/electron probe microanalysis, X-ray diffraction, transmittance, permeability towards oxygen and carbon dioxide, thermal degradation, contact angle measurement, water and vapour uptake, leachability and biocompatibility (haemolytic potential, thrombogenicity and cytotoxicity). A conventional organic plasticizer (di-isononyl phthalate) was used for comparison purposes. The results obtained showed that it was possible to change the neat PVC hydrophobicity, and consequently its water uptake capacity and plasticizer leachability, just by changing the PhIL employed and its composition. It was also possible to significantly change the thermal and mechanical properties of PVC films by choosing appropriate PhIL cation/anion combinations. However, a specific PhIL may not always be capable of simultaneously keeping and/or improving both physical properties. In addition, ionic halide salts were found to promote PVC dehydrochlorination. Finally, none of the prepared materials presented toxicity against Caco-2 cells, though pure [P(6,6,6,14)][dca] decreased HepG2 cells viability. Moreover, PVC films with [P(6,6,6,14)][dca] and [P(4,4,4,4)][Cl] were found to be haemolytic and thus these PhILs must be avoided as PVC modifiers if biomedical applications are envisaged. In conclusion, from all the PhILs tested, [P(6,6,6,14)][Tf(2)N] showed the most promising results regarding blood compatibility, leaching and permeability to gases of PVC films. The results presented are a strong indicator that adequate PhILs may be successfully employed as PVC multi-functional plasticizers for a wide range of potential applications, including those in the biomedical field.