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1.
Biomacromolecules ; 24(2): 576-591, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36599074

RESUMO

Presented in this work is the use of a molecular descriptor, termed the α parameter, to aid in the design of a series of novel, terpene-based, and sustainable polymers that were resistant to biofilm formation by the model bacterial pathogen Pseudomonas aeruginosa. To achieve this, the potential of a range of recently reported, terpene-derived monomers to deliver biofilm resistance when polymerized was both predicted and ranked by the application of the α parameter to key features in their molecular structures. These monomers were derived from commercially available terpenes (i.e., α-pinene, ß-pinene, and carvone), and the prediction of the biofilm resistance properties of the resultant novel (meth)acrylate polymers was confirmed using a combination of high-throughput polymerization screening (in a microarray format) and in vitro testing. Furthermore, monomers, which both exhibited the highest predicted biofilm anti-biofilm behavior and required less than two synthetic stages to be generated, were scaled-up and successfully printed using an inkjet "valve-based" 3D printer. Also, these materials were used to produce polymeric surfactants that were successfully used in microfluidic processing to create microparticles that possessed bio-instructive surfaces. As part of the up-scaling process, a novel rearrangement was observed in a proposed single-step synthesis of α-terpinyl methacrylate via methacryloxylation, which resulted in isolation of an isobornyl-bornyl methacrylate monomer mixture, and the resultant copolymer was also shown to be bacterial attachment-resistant. As there has been great interest in the current literature upon the adoption of these novel terpene-based polymers as green replacements for petrochemical-derived plastics, these observations have significant potential to produce new bio-resistant coatings, packaging materials, fibers, medical devices, etc.


Assuntos
Biofilmes , Terpenos , Terpenos/farmacologia , Polímeros/química , Bactérias , Metacrilatos
2.
Macromol Rapid Commun ; 42(6): e2000321, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33249682

RESUMO

The versatility of the Passerini three component reaction (Passerini-3CR) is herein exploited for the synthesis of an amphiphilic diblock copolymer, which self-assembles into polymersomes. Carboxy-functionalized poly(ethylene glycol) methyl ether is reacted with AB-type bifunctional monomers and tert-butyl isocyanide in a single process via Passerini-3CR. The resultant diblock copolymer (P1) is obtained in good yield and molar mass dispersity and is well tolerated in model cell lines. The Passerini-3CR versatility and reproducibility are shown by the synthesis of P2, P3, and P4 copolymers. The ability of the Passerini P1 polymersomes to incorporate hydrophilic molecules is verified by loading doxorubicin hydrochloride in P1DOX polymersomes. The flexibility of the synthesis is further demonstrated by simple post-functionalization with a dye, Cyanine-5 (Cy5). The obtained P1-Cy5 polymersomes rapidly internalize in 2D cell monolayers and penetrate deep into 3D spheroids of MDA-MB-231 triple-negative breast cancer cells. P1-Cy5 polymersomes injected systemically in healthy mice are well tolerated and no visible adverse effects are seen under the conditions tested. These data demonstrate that new, biodegradable, biocompatible polymersomes having properties suitable for future use in drug delivery can be easily synthesized by the Passerini-3CR.


Assuntos
Sistemas de Liberação de Medicamentos , Polímeros , Animais , Doxorrubicina/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Reprodutibilidade dos Testes
3.
Biomacromolecules ; 20(1): 90-101, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-29870241

RESUMO

A Passerini three-component polymerization was performed for the synthesis of amphiphilic star-shaped block copolymers with hydrophobic cores and hydrophilic coronae. The degree of polymerization of the hydrophobic core was varied from 5 to 10 repeating units, and the side chain ends were conjugated by performing a Passerini-3CR with PEG-isocyanide and PEG-aldehyde (950 g/mol). The resulting amphiphilic star-shaped block copolymers contained thioether groups, which could be oxidized to sulfones in order to further tune the polarity of the polymer chains. The ability of the amphiphilic copolymers to act as unimolecular micellar encapsulants was tested with the water-insoluble dye Orange II, the water-soluble dye Para Red and the macrolide antibiotic azithromycin. The results showed that the new copolymers were able to retain drug cargo at pH levels corresponding to circulating blood and selectively release therapeutically effective doses of antibiotic as measured by bacterial cell kill. The polymers were also well-tolerated by differentiated THP-1 macrophages in the absence of encapsulated drugs.


Assuntos
Materiais Biocompatíveis/síntese química , Micelas , Nanopartículas/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Azitromicina/administração & dosagem , Azitromicina/química , Linhagem Celular , Liberação Controlada de Fármacos , Humanos , Monócitos/efeitos dos fármacos , Nanopartículas/efeitos adversos , Polietilenoglicóis/química , Polimerização
4.
Biomacromolecules ; 20(5): 2135-2147, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-31013072

RESUMO

The precise synthesis of polymers derived from alkyl lactate ester acrylates is reported for the first time. Kinetic experiments were conducted to demonstrate that Cu(0) wire-catalyzed single electron transfer-living radical polymerization (SET-LRP) in alcohols at 25 °C provides a green methodology for the LRP of this forgotten class of biobased monomers. The acrylic derivative of ethyl lactate (EL) solvent and homologous structures with methyl and n-butyl ester were polymerized with excellent control over molecular weight, molecular weight distribution, and chain-end functionality. Kinetics plots in conventional alcohols such as ethanol and methanol were first order in the monomer, with molecular weight increasing linearly with conversion. However, aqueous EL mixtures were found to be more suitable than pure EL to mediate the SET-LRP process. The near-quantitative monomer conversion and high bromine chain-end functionality, demonstrated by matrix-assisted laser desorption ionization time-of-flight analysis, further allowed the preparation of innovative biobased block copolymers containing rubbery poly(ethyl lactate acrylate) poly(ELA) sequences. For instance, the poly(ELA)- b-poly(glycerol acrylate) block copolymer self-assembled in water to form stable micelles with chiral lactic acid-derived block-forming micellar core as confirmed by the pyrene-probe-based fluorescence technique. Dynamic light scattering and transmission electron microscopy measurements revealed the nanosize spherical morphology for these biobased aggregates.


Assuntos
Acrilatos , Lactatos/química , Polímeros/síntese química , Catálise , Cobre/química , Micelas , Polimerização , Polímeros/química
5.
Colloids Surf B Biointerfaces ; 236: 113828, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452625

RESUMO

Despite the success of polyethylene glycol-based (PEGylated) polyesters in the drug delivery and biomedical fields, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited chemical handles as well as highly hydrophobic nature, can restrict their effectiveness in physiological conditions of the polyester counterpart. To address these matters, an increasing amount of research has been focused towards identifying alternatives to PEG. One promising strategy involves the use of bio-derived polyols, such as glycerol. In particular, glycerol is a hydrophilic, non-toxic, untapped waste resource and as other polyols, can be incorporated into polyesters via enzymatic catalysis routes. In the present study, a systematic screening is conducted focusing on the incorporation of 1,6-hexanediol (Hex) (hydrophobic diol) into both poly(glycerol adipate) (PGA) and poly(diglycerol adipate) (PDGA) at different (di)glycerol:hex ratios (30:70; 50:50 and 70:30 mol/mol) and its effect on purification upon NPs formation. By varying the amphiphilicity of the backbone, we demonstrated that minor adjustments influence the NPs formation, NPs stability, drug encapsulation, and degradation of these polymers, despite the high chemical similarity. Moreover, the best performing materials have shown good biocompatibility in both in vitro and in vivo (whole organism) tests. As preliminary result, the sample containing diglycerol and Hex in a 70:30 ratio, named as PDGA-Hex 30%, has shown to be the most promising candidate in this small library analysed. It demonstrated comparable stability to the glycerol-based samples in various media but exhibited superior encapsulation efficiency of a model hydrophobic dye. This in-depth investigation provides new insights into the design and modification of biodegradable (di)glycerol-based polyesters, potentially paving the way for more effective and sustainable PEG-free drug delivery nano-systems in the pharmaceutical and biomedical fields.


Assuntos
Nanopartículas , Poliésteres , Poliésteres/química , Glicerol/química , Polietilenoglicóis/química , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Adipatos , Nanopartículas/química
6.
J Colloid Interface Sci ; 641: 1043-1057, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36996683

RESUMO

Sustainably derived poly(glycerol adipate) (PGA) has been deemed to deliver all the desirable features expected in a polymeric scaffold for drug-delivery, including biodegradability, biocompatibility, self-assembly into nanoparticles (NPs) and a functionalisable pendant group. Despite showing these advantages over commercial alkyl polyesters, PGA suffers from a series of key drawbacks caused by poor amphiphilic balance. This leads to weak drug-polymer interactions and subsequent low drug-loading in NPs, as well as low NPs stability. To overcome this, in the present work, we applied a more significant variation of the polyester backbone while maintaining mild and sustainable polymerisation conditions. We have investigated the effect of the variation of both hydrophilic and hydrophobic segments upon physical properties and drug interactions as well as self-assembly and NPs stability. For the first time we have replaced glycerol with the more hydrophilic diglycerol, as well as adjusting the final amphiphilic balance of the polyester repetitive units by incorporating the more hydrophobic 1,6-n-hexanediol (Hex). The properties of the novel poly(diglycerol adipate) (PDGA) variants have been compared against known polyglycerol-based polyesters. Interestingly, while the bare PDGA showed improved water solubility and diminished self-assembling ability, the Hex variation demonstrated enhanced features as a nanocarrier. In this regard, PDGAHex NPs were tested for their stability in different environments and for their ability to encode enhanced drug loading. Moreover, the novel materials have shown good biocompatibility in both in vitro and in vivo (whole organism) experiments.


Assuntos
Glicerol , Nanopartículas , Sistemas de Liberação de Medicamentos , Poliésteres/química , Preparações Farmacêuticas , Adipatos/química , Nanopartículas/química , Portadores de Fármacos/química
7.
J Mater Chem B ; 10(20): 3895-3905, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35470847

RESUMO

New materials chemistries are urgently needed to overcome the limitations of existing biomedical materials in terms of preparation, functionality and versatility, and also in regards to their compatibility with biological environments. Here, we show that Passerini reactions are especially suited for the preparation of drug delivery materials, as with relatively few steps, polymers can be synthesized with functionality installed enabling drug conjugation and encapsulation, self-assembly into micellar or vesicular architectures, and with facile attachment triggerable chemistries. The polymers can be made with a variety of building blocks and assemble into nanoparticles, which are rapidly internalized in triple negative breast cancer (TNBC) cells. In addition, the polymers transport drug molecules efficiently through 3D cell cultures, and when designed with chemistries allowing pH-mediated release, exhibit greater efficacy against TNBC cells compared to the parent drug.


Assuntos
Nanopartículas , Pró-Fármacos , Neoplasias de Mama Triplo Negativas , Sistemas de Liberação de Medicamentos , Humanos , Polímeros/uso terapêutico , Pró-Fármacos/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
8.
Sci Rep ; 12(1): 18411, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319651

RESUMO

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.


Assuntos
Hidrodinâmica , Polímeros , Ácido Oleico , Ultracentrifugação
9.
Bioconjug Chem ; 22(2): 156-68, 2011 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-21222431

RESUMO

Multifunctional and modular block copolymers prepared from biocompatible monomers and linked by a bioreducible disulfide linkage have been prepared using a combination of ring-opening and atom-transfer radical polymerizations (ATRP). The presence of terminal functionality via ATRP allowed cell-targeting folic acid groups to be attached in a controllable manner, while the block copolymer architecture enabled well-defined nanoparticles to be prepared by a water-oil-water double emulsion procedure to encapsulate DNA with high efficiency. Gene delivery assays in a Calu-3 cell line indicated specific folate-receptor-mediated uptake of the nanoparticles, and triggered release of the DNA payload via cleavage of the disulfide link resulted in enhanced transgene expression compared to nonbioreducible analogues. These materials offer a promising and generic means to deliver a wide variety of therapeutic payloads to cells in a selective and tunable way.


Assuntos
Técnicas de Transferência de Genes , Nanopartículas/química , Linhagem Celular Tumoral , DNA/química , Ácido Fólico/química , Humanos , Luciferases/análise , Luciferases/metabolismo , Modelos Biológicos , Estrutura Molecular , Plasmídeos/química , Polimerização , Polímeros/síntese química , Polímeros/química , Estereoisomerismo
10.
Biomacromolecules ; 12(6): 2126-36, 2011 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-21561067

RESUMO

Pseudomonas mendocina was found to produce a unique homopolymer of poly(3-hydroxyoctanoate), P(3HO), rather than a copolymer, when grown on sodium octanoate as the sole carbon source. Although this polymer has been produced by other organisms, interestingly this is the first time an absolute homopolymer has been produced by a wild type organism. In addition, a detailed study on the effects of different extraction methods on the yield, molecular weight, thermal properties, and lipopolysaccharide content of P(3HO) has been carried out. The organism was able to accumulate P(3HO) up to 31.38% of its dry cell weight within 48 h in mineral salt medium. Characterization of the monomer was carried out using FTIR, GC-MS, (13)C, (1)H, and HSQC NMR spectroscopy. The polymer had a crystallinity of 37.5%, Young's modulus value of 11.6 MPa and contact angle of 77.3°. Microstructural studies of solvent cast polymer films revealed a smooth surface topography with a root-mean-square roughness value of 0.238 µm.


Assuntos
Materiais Biocompatíveis/química , Poliésteres/isolamento & purificação , Poli-Hidroxialcanoatos/isolamento & purificação , Pseudomonas mendocina/química , Cristalização , Meios de Cultura/química , Meios de Cultura/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Módulo de Elasticidade , Cromatografia Gasosa-Espectrometria de Massas , Lipopolissacarídeos/análise , Lipopolissacarídeos/biossíntese , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Peso Molecular , Poliésteres/química , Poliésteres/metabolismo , Poli-Hidroxialcanoatos/biossíntese , Poli-Hidroxialcanoatos/metabolismo , Infecções por Pseudomonas/microbiologia , Pseudomonas mendocina/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
11.
Pharm Res ; 28(7): 1668-82, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21394661

RESUMO

PURPOSE: Novel biodegradable and mucoadhesive PLGA/chitosan microparticles with the potential for use as a controlled release gastroretentive system were manufactured using supercritical CO(2) (scCO(2)) by the Particle Gas Saturated System (PGSS) technique (also called CriticalMix(TM)). METHODS: Microparticles were produced from PLGA with the addition of mPEG and chitosan in the absence of organic solvents, surfactants and crosslinkers using the PGSS technique. Microparticle formulations were morphologically characterized by scanning electron microscope; particle size distribution was measured using laser diffraction. Microparticle surface was analyzed using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) to evaluate the presence of chitosan on the surface. Mucoadhesiveness of the microparticles was evaluated in vitro using a mucin assay employing two different kinds of mucin (Mucin type III and I-S) with different degrees of sialic acid contents, 0.5-1.5% and 9-17%, respectively. RESULTS: The two analytical surface techniques (XPS and ToF-SIMS) demonstrated the presence of the chitosan on the surface of the particles (<100 µm), dependent on the polymer composition of the microparticles. The interaction between the mucin solutions and the PLGA/chitosan microparticles increased significantly with an increasing concentration of mucin and chitosan. CONCLUSIONS: The strong interaction of mucin with the chitosan present on the surface of the particles suggests a potential use of the mucoadhesive carriers for gastroretentive and oral controlled drug release.


Assuntos
Materiais Biocompatíveis/química , Quitosana/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Adesividade , Animais , Cromatografia com Fluido Supercrítico , Humanos , Microscopia Eletrônica de Varredura , Mucinas/química , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Propriedades de Superfície
12.
J Mater Sci Mater Med ; 22(8): 1975-83, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21667187

RESUMO

Injection of polymeric microparticles is the final step in the drug delivery process. Experience has shown that blockage of the syringe mechanism can be a problem under certain conditions leading to poor control of the final product. Particle size and shape are postulated to be significant factors. In this article 2D Discrete element model (DEM) simulations of circles and semi-circles are used to demonstrate the effect of shape on blockage of the syringe mechanism. To corroborate the calculations, a range of experiments on glass spheres and polymers show good agreement with simulations of normally distributed particle sizes. A similar scenario is also briefly modelled in 3D DEM showing similar trends.


Assuntos
Microesferas , Agulhas , Tamanho da Partícula , Polímeros/administração & dosagem , Seringas , Microscopia Eletrônica de Varredura
13.
Angew Chem Int Ed Engl ; 50(42): 9852-6, 2011 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-21922612

RESUMO

Double agents: dual-action polymers are able to sequester rapidly the marine organism Vibrio harveyi from suspension, while at the same time quenching bacterial quorum sense (QS) signals. The potency of the polymers is assessed by cell aggregation experiments and competitive binding assays against a QS signal precursor, and their effect on bacterial behavior is shown by means of bioluminescence.


Assuntos
Polímeros/síntese química , Polímeros/farmacologia , Percepção de Quorum/efeitos dos fármacos , Vibrio/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Estrutura Molecular , Polímeros/química , Especificidade da Espécie , Relação Estrutura-Atividade , Propriedades de Superfície , Vibrio/citologia
14.
Carbohydr Polym ; 253: 117277, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278948

RESUMO

Thermoplastic, polysaccharide-based plastics are environmentally friendly. However, typical shortcomings include lack of water resistance and poor mechanical properties. Nanocomposite manufacturing using pure, highly linear, polysaccharides can overcome such limitations. Cast nanocomposites were fabricated with plant engineered pure amylose (AM), produced in bulk quantity in transgenic barley grain, and cellulose nanofibers (CNF), extracted from agrowaste sugar beet pulp. Morphology, crystallinity, chemical heterogeneity, mechanics, dynamic mechanical, gas and water permeability, and contact angle of the films were investigated. Blending CNF into the AM matrix significantly enhanced the crystallinity, mechanical properties and permeability, whereas glycerol increased elongation at break, mainly by plasticizing the AM. There was significant phase separation between AM and CNF. Dynamic plasticizing and anti-plasticizing effects of both CNF and glycerol were demonstrated by NMR demonstrating high molecular order, but also non-crystalline, and evenly distributed 20 nm-sized glycerol domains. This study demonstrates a new lead in functional polysaccharide-based bioplastic systems.


Assuntos
Amilose/química , Plásticos Biodegradáveis/química , Celulose/química , Nanocompostos/química , Nanofibras/química , Extratos Vegetais/química , Amilose/isolamento & purificação , Beta vulgaris/química , Celulose/isolamento & purificação , Cristalização , Farinha , Glicerol/química , Hordeum/química , Permeabilidade , Plastificantes/química , Maleabilidade , Amido/química , Resistência à Tração , Temperatura de Transição
15.
Biomacromolecules ; 11(11): 2854-65, 2010 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-20873757

RESUMO

The aim of the present work is to investigate if conditions can be devised where PEGylation of chitosan would reduce its toxicity toward the nasal mucosa while maintaining its ability to open the cellular tight junctions and, consequently, produce an enhancement of macromolecular permeability. A series of mPEG-g-chitosan copolymers with varying levels of mPEG substitution, mPEG molecular weight, and chitosan molecular weight were synthesized by grafting carboxylic acid-terminated mPEGs (Mw 1.9 and 5.0 × 10(3) g mol(-1)) to chitosans (Mw 28.9 and 82.0 × 10(3) g mol(-1)) using a NHS/EDC coupling system. The synthesized mPEG-g-chitosans were fully characterized using a number of techniques, including FT-IR, (1)H NMR, and SEC-MALLS and their physicochemical properties were analyzed by TGA and DSC. Thereafter, the conjugates were tested for their cytotoxicity and tight junction modulating property in a relevant cell model, a mucus producing Calu-3 monolayer. mPEG-g-chitosan conjugates exhibited reduced toxicity toward cells, as compared to unmodified chitosan counterparts. Furthermore, the conjugates demonstrated a dramatic effect on cell monolayer transepithelial electrical resistance (TEER) and enhancement of permeability of model macromolecules. TEER and permeability-enhancing effects, as measurable indicators of tight junction modulation, were found to be pH-dependent and were notably more pronounced than those exhibited by unmodified chitosans. This work therefore demonstrates that conditions can be contrived where PEGylation improves the toxicity profile of chitosan, while preserving its effect on epithelial tight junctions in the nose.


Assuntos
Permeabilidade da Membrana Celular/efeitos dos fármacos , Quitosana/farmacologia , Quitosana/toxicidade , Polietilenoglicóis/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quitosana/síntese química , Quitosana/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Solubilidade , Relação Estrutura-Atividade
16.
Biomacromolecules ; 10(4): 822-8, 2009 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-19226106

RESUMO

Thermoresponsive and photocrosslinkable polymers can be used as injectable scaffolds in tissue engineering to yield gels in situ with enhanced mechanical properties and stability. They allow easy handling and hold their shapes prior to photopolymerization for clinical practice. Here we report a novel copolymer with both thermoresponsive and photocrosslinkable properties via a facile one-step deactivation enhanced atom transfer radical polymerization (ATRP) using poly(ethylene glycol) methyl ether methylacrylate (PEGMEMA, M(n) = 475) and poly(propylene glycol) methacrylate (PPGMA, M(n) = 375) as monofunctional vinyl monomers and up to 30% of ethylene glycol dimethacrylate (EGDMA) as multifunctional vinyl monomer. The resultant PEGMEMA-PPGMA-EGDMA copolymers have been characterized by gel permeation chromatography (GPC) and 1H NMR analysis, which demonstrate their multivinyl functionality and hyperbranched structures. These water-soluble copolymers show lower critical solution temperature (LCST) behavior at 32 degrees C, which is comparable to poly(N-isopropylacrylamide) (PNIPAM). The copolymers can also be cross-linked by photopolymerization through their multivinyl functional groups. Rheological studies clearly demonstrate that the photocrosslinked gels formed at a temperature above the LCST have higher storage moduli than those prepared at a temperature below the LCST. Moreover, the cross-linking density of the gels can be tuned to tailor their porous structures and mechanical properties by adjusting the composition and concentration of the copolymers. Hydrogels with a broad range of storage moduli from 10 to 400 kPa have been produced.


Assuntos
Resinas Acrílicas/síntese química , Resinas Acrílicas/farmacologia , Hidrogéis/química , Metacrilatos/química , Éteres Metílicos/química , Polímeros/síntese química , Polímeros/farmacologia , Resinas Acrílicas/química , Reagentes de Ligações Cruzadas/farmacologia , Teste de Materiais , Fotoquímica , Polímeros/química , Estresse Mecânico , Temperatura , Raios Ultravioleta
17.
Biomacromolecules ; 10(10): 2895-903, 2009 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-19746967

RESUMO

Photo-cross-linked hydrogels from thermoresponsive polymers can be used as advanced injectable biomaterials via a combination of physical interaction (in situ thermal gelation) and covalent cross-links (in situ photopolymerization). This can lead to gels with significantly enhanced mechanical properties compared to non-photo-cross-linked thermoresponsive hydrogels. Moreover, the thermally phase-separated gels have attractive advantages over non-thermoresponsive gels because thermal gelation upon injection allows easy handling and holds the shape of the gels prior to photopolymerization. In this study, water-soluble thermoresponsive copolymers containing multiple methacrylate groups were synthesized via one-step deactivation enhanced atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M(n) = 475), poly(propylene glycol) methacrylate (PPGMA, M(n) = 375), and ethylene glycol dimethacrylate (EGDMA) and were used to form covalent cross-linked hydrogels by photopolymerization. The cross-linking density was found to have a significant influence on the mechanical and swelling properties of the photo-cross-linked gels. Release studies using lysozyme as a model protein demonstrated a sustained release profile that varied dependent on the copolymer composition, cross-linking density, and the temperature. Mouse C2C12 myoblast cells were cultured in the presence of the copolymers at concentrations up to 1 mg/mL. It was found that the majority of the cells remained viable, as assessed by Alamar Blue, lactate dehydrogenase (LDH), and Live/Dead cell viability/cytotoxicity assays. These studies demonstrate that thermoresponsive PEGMEMA-PPGMA-EGDMA copolymers offer potential as in situ photopolymerizable materials for tissue engineering and drug delivery applications through a combination of facile synthesis, enhanced mechanical properties, tunable cross-linking density, low cytotoxicity, and accessible functionality for further structure modifications.


Assuntos
Resinas Acrílicas/química , Hidrogéis/química , Metacrilatos/química , Proteínas/química , Microscopia Eletrônica de Varredura , Fotoquímica , Reologia , Espectrofotometria Ultravioleta
18.
J Mater Chem B ; 7(34): 5222-5229, 2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31369021

RESUMO

A bis-epoxide monomer was synthesised in two steps from (R)-carvone, a terpenoid renewable feedstock derived from spearmint oil, and used to prepare ß-aminoalcohol oligomers in polyaddition reactions with bis-amines without requiring solvent or catalyst. A sub-set of the resultant materials were readily water soluble and were investigated for antifungal activity in combination with the fungicide iodopropynyl-butylcarbamate (IPBC) or the antifungal drug amphotericin B. The oligo-(ß-aminoalcohol)s alone were inactive against Trichoderma virens and Candida albicans but in combination with IPBC and amphotericin B demonstrated synergistic growth-inhibition of both fungi. Quantitative analysis showed that the presence of the terpene-based oligomers decreased the minimum inhibitory concentration (MIC) of IPBC by up to 64-fold and of amphotericin B by 8-fold. The efficacy of the combined formulation was further demonstrated with agar disk diffusion assays, which revealed that IPBC and amphotericin B reduced the growth of the fungi, as shown by zones of inhibition, to a greater extent when in the presence of the oligo-(ß-aminoalcohol)s. These data suggest potential future use of these renewable feedstock derived oligomers in antifungal material and related biomedical applications.


Assuntos
Aminas/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Resinas Epóxi/farmacologia , Terpenos/farmacologia , Trichoderma/efeitos dos fármacos , Aminas/química , Antifúngicos/química , Resinas Epóxi/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Tamanho da Partícula , Propriedades de Superfície , Terpenos/química
19.
J Pharm Sci ; 108(2): 811-814, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30267781

RESUMO

Chronic cancer pain remains prevalent and severe for many patients, particularly in those with advanced disease. The effectiveness of analgesic/adjuvant drug treatments in routine practice has changed little in the last 30 years. To address these issues herein, we have developed sustained-release poly(lactic-co-glycolic acid) microparticles of hydromorphone for intrathecal injection aimed at producing prolonged periods of satisfactory analgesia in patients, as a novel strategy for alleviation of intractable cancer-related pain. These hydromorphone-loaded microparticles were produced successfully using organic solvent-free supercritical fluid polymer encapsulation. Drug loading at 9.2% and encapsulation efficacy at 92% were achieved for particles in the desired size range (20-45 µm) with sustained release over a 5-week period in vitro.


Assuntos
Analgésicos Opioides/administração & dosagem , Preparações de Ação Retardada/química , Hidromorfona/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Analgésicos Opioides/química , Dor do Câncer/tratamento farmacológico , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Hidromorfona/química , Injeções Espinhais
20.
Adv Drug Deliv Rev ; 60(3): 373-87, 2008 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-18069079

RESUMO

Supercritical CO(2) has the potential to be an excellent environment within which controlled release polymers and dry composites may be formed. The low temperature and dry conditions within the fluid offer obvious advantages in the processing of water, solvent or heat labile molecules. The low viscosity and high diffusivity of scCO(2) offer the possibility of novel processing routes for polymer drug composites, but there are still technical challenges to overcome. Moreover, the low solubility of most drug molecules in scCO(2) presents both challenges and advantages. This review explores the current methods that use high pressure and scCO(2) for the production of drug delivery systems and the more specialized application of the fluid in the formation of highly porous tissue engineering scaffolds.


Assuntos
Dióxido de Carbono/química , Sistemas de Liberação de Medicamentos/métodos , Polímeros/química , Engenharia Tecidual/métodos , Química Farmacêutica/métodos , Polímeros/síntese química , Solubilidade , Tecnologia Farmacêutica/métodos
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