RESUMEN
Biobased natural polymers, including polymers of natural origin such as casein, are growing rapidly in the light of the environmental pollution caused by many mass-produced commercial synthetic polymers. Although casein has interesting intrinsic properties, especially for the food industry, numerous chemical reactions have been carried out to broaden the range of its properties, most of them preserving casein's nontoxicity and biodegradability. New conjugates and graft copolymers have been developed especially by Maillard reaction of the amine functions of the casein backbone with the aldehyde functions of sugars, polysaccharides, or other molecules. Carried out with dialdehydes, these reactions lead to the cross-linking of casein giving three-dimensional polymers. Acylation and polymerization of various monomers initiated by amine functions are also described. Other reactions, far less numerous, involve alcohol and carboxylic acid functions in casein. This review provides an overview of casein-based conjugates and graft copolymers, their properties, and potential applications.
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Caseínas , Polímeros , Caseínas/química , Polímeros/química , Polisacáridos/química , AminasRESUMEN
Hydrophilic chitosan (CHT) and hydrophobic polyε-caprolactone (PCL) are well-known biocompatible and biodegradable polymers that have many applications in the biomedical and pharmaceutical fields. But the mixtures of these two compounds are considered incompatible, which makes them not very interesting. To avoid this problem and to further extend the properties of these homopolymers, the synthesis of a new graft copolymer, the fully biodegradable amphiphilic poly(ε-caprolactone-g-chitosan) (PCL-g-CHT) is described, with an unusual "reverse" structure formed by a PCL backbone with CHT grafts, unlike the "classic" CHT-g-PCL structure with a CHT main chain and PCL grafts. This copolymer is prepared via a copper-catalyzed 1,3-dipolar Huisgen cycloaddition between propargylated PCL (PCL-yne) and a new azido-chitosan (CHT-N3 ). In order to obtain an amphiphilic copolymer regardless of the pH, chitosan oligomers, soluble at any pH, are prepared and used. The amphiphilic PCL-g-CHT copolymer spontaneously self-assembles in water into nanomicelles that may incorporate hydrophobic drugs to give novel drug delivery systems.
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Quitosano , Quitosano/química , Polímeros , Poliésteres/química , Polietilenglicoles/químicaRESUMEN
Sodium caseinate is a well-known amphiphilic protein derived from natural products currently used for the preparation of edible films. To improve some properties, especially to decrease the hydrophilicity and water solubility of the caseinate, the covalent grafting of a hydrophobic edible fatty acid, namely oleic acid, onto caseinate, appears to be a solution. We describe a new synthesis method for the chemical modification of sodium caseinate involving the synthesis of an acid chloride derivative from oleic acid and a phase transfer catalysis reaction in a biphasic medium. Under these conditions, free amine and alcohol groups of the caseinate are likely to be grafted with a fairly high (>50 %) substitution degree. The caseinate derivative is finely characterized, in particular by DOSY NMR, to assess the formation of a casein/oleic acid grafted compound as well as the absence of residual oleic acid.
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Caseínas , Ácido Oléico , Caseínas/química , Ácidos Grasos , Solubilidad , ÁcidosRESUMEN
Synthetic biopolymers are attractive alternatives to biobased polymers, especially because they rarely induce an immune response in a living organism. Poly ε-caprolactone (PCL) is a well-known synthetic aliphatic polyester universally used for many applications, including biomedical and environmental ones. Unlike poly lactic acid (PLA), PCL has no chiral atoms, and it is impossible to play with the stereochemistry to modify its properties. To expand the range of applications for PCL, researchers have investigated the possibility of grafting polymer chains onto the PCL backbone. As the PCL backbone is not functionalized, it must be first functionalized in order to be able to graft reactive groups onto the PCL chain. These reactive groups will then allow the grafting of new reagents and especially new polymer chains. Grafting of polymer chains is mainly carried out by "grafting from" or "grafting onto" methods. In this review we describe the main structures of the graft copolymers produced, their different synthesis methods, and their main characteristics and applications, mainly in the biomedical field.
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Poliésteres , Polímeros , Poliésteres/química , Polímeros/química , Caproatos/química , Lactonas/químicaRESUMEN
This work reports on a novel polyester copolymer containing poly(dopamine), a synthetic analogue of natural melanin, evaluated in a sustained-release drug delivery system for ocular intravitreal administration of drugs. More specifically, a graft copolymer of poly(ε-caprolactone)-graft-poly(dopamine) (PCL-g-PDA) has been synthesized and was shown to further extend the drug release benefits of state-of-the-art biodegradable intravitreal implants composed of poly(lactide) and poly(lactide-co-glycolide). The innovative biomaterial combines the documented drug-binding properties of melanin naturally present in the eye, with the established ocular tolerability and biodegradation of polyester implants. The PCL-g-PDA copolymer was obtained by a two-step modification of PCL with a final PDA content of around 2-3 wt % and was fully characterized by size exclusion chromatography, NMR, and diffusion ordered NMR spectroscopy. The thermoplastic nature of PCL-g-PDA allowed its simple processing by hot-melt compression molding to prepare small implants. The properties of unmodified PCL and PCL-g-PDA implants were studied and compared in terms of thermal properties (differential scanning calorimetry), thermal stability (thermogravimetry analysis), degradability, and in vitro cytotoxicity. PCL and PCL-g-PDA implants exhibited similar degradation properties in vitro and were both stable under physiological conditions over 110 days. Likewise, both materials were non-cytotoxic toward L929 and ARPE-19 cells. The drug loading and in vitro release properties of the new materials were investigated with dexamethasone (DEX) and ciprofloxacin hydrochloride (CIP) as representative drugs featuring low and high melanin-binding affinities, respectively. In comparison to unmodified PCL, PCL-g-PDA implants showed a significant extension of drug release, most likely because of specific drug-catechol interaction with the PDA moieties of the copolymer. The present study confirms the advantages of designing PDA-containing polyesters as a class of biodegradable and biocompatible thermoplastics that can modulate and remarkably extend the drug release kinetics thanks to their unique drug-binding properties, especially, but not limited to, for ocular applications.
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Melaninas , Poliglactina 910 , Materiales Biocompatibles , Catecoles , Ciprofloxacina , Preparaciones de Acción Retardada/farmacología , Dexametasona , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Indoles , Poliésteres/química , Polietilenglicoles/química , PolímerosRESUMEN
As a potential replacement for petroleum-based plastics, biodegradable bio-based polymers such as poly(lactic acid) (PLA) have received much attention in recent years. PLA is a biodegradable polymer with major applications in packaging and medicine. Unfortunately, PLA is less flexible and has less impact resistance than petroleum-based plastics. To improve the mechanical properties of PLA, PLA-based blends are very often used, but the outcome does not meet expectations because of the non-compatibility of the polymer blends. From a chemical point of view, the use of graft copolymers as a compatibilizer with a PLA backbone bearing side chains is an interesting option for improving the compatibility of these blends, which remains challenging. This review article reports on the various graft copolymers based on a PLA backbone and their syntheses following two chemical strategies: the synthesis and polymerization of modified lactide or direct chemical post-polymerization modification of PLA. The main applications of these PLA graft copolymers in the environmental and biomedical fields are presented.
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Materiales Biocompatibles , Petróleo , Materiales Biocompatibles/química , Plásticos , Poliésteres/química , Polímeros/químicaRESUMEN
A new fully biodegradable "reverse" oligosaccharide-based amphiphilic graft copolymer structure with a hydrophobic backbone and hydrophilic side chains, poly(ε-caprolactone)-g-dextran (PCL-g-Dex) was synthetized. For this purpose, "clickable" propargylated PCL (PCL-yne) and azido-dextran (Dex-N3) were prepared to further synthesize PCL-g-Dex copolymer by a Huisgen's cycloaddition. This "reverse" copolymer architecture self-assembled in biodegradable nano-carriers, in the shape of dynamic polymeric micelles, and were loaded with doxorubicin (Dox) anti-cancer drug. Dox-loaded micelles showed different drug releases depending on the pH. Cytotoxicity tests showed that Dox-loaded micelles can selectively kill colon cancer cells (HCT-116) while they have no cytotoxic effect towards healthy cells (CCD-45SK). Fluorescent micelles based on FITC-labelled PCL-g-Dex copolymer were used for fluorescence imaging and flow cytometry assays. These experiments proved the effective and specific internalization of micelles by cancer cells, whereas healthy cells showed a very poor uptake. These results show that PCL-g-Dex micelles may be a promising Dox nano-carrier in cancer chemotherapy.
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Antibióticos Antineoplásicos/farmacología , Dextranos/química , Doxorrubicina/farmacología , Nanopartículas/química , Poliésteres/química , Antibióticos Antineoplásicos/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Micelas , Estructura Molecular , Tamaño de la Partícula , Relación Estructura-Actividad , Propiedades de SuperficieRESUMEN
The use of double-hydrophilic block copolymers (DHBCs) in biomedical applications is limited by their lack of degradability. This additional functionality has been obtained in the past through multistep chemical strategies associated with low yields. In this work, a series of DHBCs composed of a bioeliminable poly(ethylene glycol) (PEG) block and hydrolyzable functional poly(ε-caprolactone) (PCL) blocks bearing carboxylic (PEG-b-PCL(COOH)), amino (PEG-b-PCL(NH2)), or hydroxyl side groups (PEG-b-PCL(OH)) is synthesized in only three steps. DHBCs with 50% substitution degree with respect to the CL units are obtained for all functional groups. The pH-dependent self-assembly behavior of the DHBCs is studied showing critical micelle concentration (CMC) variations by a factor of 2 upon pH changes and micellar mean diameter variations of 20-30%. The potential of these partly degradable DHBCs as drug-loaded polyion complex micelles is further exemplified with the PEG-b-PCL(COOH) series that is associated with the positively charged anticancer drug doxorubicin (DOX). Encapsulation efficiencies, drug loadings, pH-controlled release, and cytotoxicity of the DOX-loaded micelles toward cancer cells are demonstrated. This set of data confirms the interest of the proposed straightforward chemical strategy to generate fully bioeliminable and partly degradable DHBCs with potential as pH-responsive drug-delivery systems.
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Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Poliésteres/química , Polímeros/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Química Clic , Doxorrubicina/administración & dosificación , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/farmacocinética , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Humanos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Lactonas/química , Células MCF-7 , Micelas , Peso Molecular , Polietilenglicoles/química , Polímeros/administración & dosificación , Polímeros/síntesis química , SolucionesRESUMEN
Intrauterine adhesions lead to partial or complete obliteration of the uterine cavity and have life-changing consequences for women. The leading cause of adhesions is believed to be loss of stroma resulting from trauma to the endometrium after surgery. Adhesions are formed when lost stroma is replaced by fibrous tissue that join the uterine walls. Few effective intrauterine anti-adhesion barriers for gynecological surgery exist. We designed a degradable anti-adhesion medical device prototype to prevent adhesion formation and recurrence and restore uterine morphology. We focused on ideal degradation time for complete uterine re-epithelialization for optimal anti-adhesion effect and clinical usability. We developed a triblock copolymer prototype [poly(lactide) combined with high molecular mass poly(ethylene oxide)]. Comparative pre-clinical studies demonstrated in vivo anti-adhesion efficacy. Ease of introduction and optimal deployment in a human uterus confirmed clinical usability. This article provides preliminary data to develop an intrauterine medical device and conduct a clinical trial.
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Diseño de Equipo , Adherencias Tisulares/prevención & control , Enfermedades Uterinas/metabolismo , Útero/patología , Útero/cirugía , Adulto , Animales , Adhesión Celular , Colágeno , Endometrio/patología , Femenino , Humanos , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Poliésteres/química , Polietilenglicoles/química , Distribución Aleatoria , Ratas , Ratas Wistar , Recurrencia , ViscosidadRESUMEN
Fast in situ forming, chemically crosslinked hydrogels were prepared by the amidation reaction between N-succinimidyl ester end groups of multi-armed poly(ethylene glycol) (PEG) and amino surface groups of poly(amido amine) (PAMAM) dendrimer generation 2.0. To control the properties of the PEG/PAMAM hydrogels, PEGs were used with different arm numbers (4 or 8) as well as different linkers (amide or ester) between the PEG arms and their terminal N-succinimidyl ester groups. Oscillatory rheology measurements showed that the hydrogels form within seconds after mixing the PEG and PAMAM precursor solutions. The storage moduli increased with crosslink density and reached values up to 2.3â¯kPa for hydrogels based on 4-armed PEG. Gravimetrical degradation experiments demonstrated that hydrogels with ester linkages between PEG and PAMAM degrade within 2â¯days, whereas amide-linked hydrogels were stable for several months. The release of two different model drugs (fluorescein isothiocyanate-dextran with molecular weights of 4·103 and 2·106 g/mol, FITC-DEX4K and FITC-DEX2000K, respectively) from amide-linked hydrogels was characterized by an initial burst followed by diffusion-controlled release, of which the rate depended on the size of the drug. In contrast, the release of FITC-DEX2000K from ester-containing hydrogels was governed mainly by degradation of the hydrogels and could be modulated via the ratio between ester and amide linkages. In vitro cytotoxicity experiments indicated that the PEG/PAMAM hydrogels are non-toxic to mouse fibroblasts. These in situ forming PEG/PAMAM hydrogels can be tuned with a broad range of mechanical, degradation and release properties and therefore hold promise as a platform for the delivery of therapeutic agents.
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Dendrímeros/química , Portadores de Fármacos/química , Liberación de Fármacos , Hidrogeles/química , Polietilenglicoles/química , Animales , Línea Celular , Dendrímeros/toxicidad , Dextranos/administración & dosificación , Dextranos/farmacocinética , Portadores de Fármacos/toxicidad , Composición de Medicamentos/métodos , Estabilidad de Medicamentos , Fibroblastos , Fluoresceína-5-Isotiocianato/administración & dosificación , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/farmacocinética , Hidrogeles/toxicidad , Ratones , Polietilenglicoles/toxicidad , Reología , Factores de Tiempo , Pruebas de ToxicidadRESUMEN
HYPOTHESIS: The presence of pendant thioether groups on poly(ethylene glycol)-poly(N(2-hydroxypropyl) methacrylamide) (PEG-P(HPMA)) block copolymers allows for platinum-mediated coordinative micellar core-crosslinking, resulting in enhanced micellar stability and stimulus-responsive drug delivery. EXPERIMENTS: A new PEG-P(HPMA) based block copolymer with pendant 4-(methylthio)benzoyl (MTB) groups along the P(HPMA) block was synthesized by free radical polymerization of a novel HPMA-MTB monomer using a PEG based macro-initiator. As crosslinker the metal-organic linker [ethylenediamineplatinum(II)]2+ was used, herein called Lx, which is a coordinative linker molecule that has been used for the conjugation of drug molecules to a number of synthetic or natural carrier systems such as hyperbranched polymers and antibodies. FINDINGS: The introduction of Lx in the micellar core results in a smaller size, a lower critical micelle concentration and a better retention of the hydrophobic drug curcumin thanks to coordination bonds between the central platinum atom of Lx and thioether groups on different polymer chains. The drug release from Lx crosslinked micelles is significantly accelerated under conditions mimicking the intracellular environment due to competitive coordination and subsequent micellar de-crosslinking. Because of their straightforward preparation and favorable drug release characteristics, core-crosslinked Lx PEG-P(HPMA) micelles hold promise as a versatile nanomedicine platform.
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Reactivos de Enlaces Cruzados/química , Sistemas de Liberación de Medicamentos , Metacrilatos/química , Compuestos Organoplatinos/química , Polietilenglicoles/química , Reactivos de Enlaces Cruzados/síntesis química , Ligandos , Micelas , Estructura Molecular , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Advanced drug delivery systems (DDS) are easily designed following a photoiterative strategy. Multifunctional polymers are obtained by coupling building blocks of interest to an alkynated poly(ε-caprolactone) (PCL) platform via an efficient thiol-yne photoaddition. Fine-tuning over the design is achieved, as illustrated with targeting and enzyme-responsive DDS.
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Sistemas de Liberación de Medicamentos/métodos , Procesos Fotoquímicos , Poliésteres/química , Polietilenglicoles/química , Alquinos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Curcumina/administración & dosificación , Curcumina/química , Células HEK293 , Humanos , Nanoestructuras/administración & dosificación , Nanoestructuras/química , Compuestos de Sulfhidrilo/químicaRESUMEN
HYPOTHESIS: The functionalization of poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) block copolymers with moieties allowing for core-crosslinking is expected to result in improved micellar stability and drug delivery properties. EXPERIMENTS: PEG-(PCL)8 star block copolymers were functionalized with pendant benzylthioether (BTE) groups by applying an anionic post-polymerization modification technique followed by photoradical thiol-yne addition of benzyl mercaptan. The micellar properties of PEG-(PCL)8 and PEG-(PCL-BTE)8 were studied and compared in terms of critical micelle concentration (CMC), size, morphology, drug loading and release and in vitro cytotoxicity. FINDINGS: In comparison with unmodified PEG-(PCL)8 micelles, PEG-(PCL-BTE)8 micelles exhibited a 15-fold lower CMC, a 15-fold smaller size and a 50% higher drug loading and encapsulation efficiency thanks to the presence of pendant benzyl groups which provide the possibility for micellar core-crosslinking via supramolecular π-π stacking and additional hydrophobic interactions. Whereas the PEG-(PCL)8 micelles showed significant aggregation during in vitro cytotoxicity experiments, the PEG-(PCL-BTE)8 micelles showed no signs of aggregation and were capable of solubilizing high concentrations of curcumin, resulting in a significant decrease in MCF-7 cell viability after 48â¯h. Their ease of synthesis combined with promising results regarding drug delivery make the PEG-(PCL-BTE)8 micelles appealing for application in the field of encapsulation.
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Antineoplásicos/farmacología , Curcumina/farmacología , Sistemas de Liberación de Medicamentos , Lactonas/química , Polietilenglicoles/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Curcumina/síntesis química , Curcumina/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células MCF-7 , Micelas , Estructura MolecularRESUMEN
The sector of implantable medical devices is a growing sector of health products especially dynamic in the field of research. To improve the management of patients and to meet clinical requirements, researchers are developing new types of medical devices. They use different families of biomaterials presenting various chemical and physical characteristics in order for providing clinicians with health products optimized for biomedical applications. In this article, we aim to show how, starting from a family of biomaterials (degradable polymers), it is possible to design an implantable medical device for the therapeutic management of the failure of anterior cruciate ligament. The main steps leading to the design of a total ligament reinforcement are detailed. They range from the synthesis and characterization of degradable polymer to the shaping of the knitted implant, through the assessment of the study of the impact of sterilization on mechanical properties and checking cytocompatibility.
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Implantes Absorbibles , Plásticos Biodegradables , Diseño de Equipo/métodos , Ligamentos/cirugía , Procedimientos de Cirugía Plástica , Polímeros/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Materiales Biocompatibles/uso terapéutico , Plásticos Biodegradables/síntesis química , Plásticos Biodegradables/química , Plásticos Biodegradables/uso terapéutico , Humanos , Polímeros/síntesis química , Procedimientos de Cirugía Plástica/métodos , Procedimientos de Cirugía Plástica/tendencias , Medicina Regenerativa/métodos , Medicina Regenerativa/tendenciasRESUMEN
The aim of this study was to prepare a new knitted scaffold from PLA-Pluronic block copolymers for anterior cruciate ligament reconstruction. The impact of sterilization methods (beta-ray and gamma-ray sterilization) on copolymers was first evaluated in order to take into account the possible damages due to the sterilization process. Beta-ray radiation did not significantly change mechanical properties in contrast to gamma-ray sterilization. It was shown that ACL cells proliferate onto these copolymers, demonstrating their cytocompatibility. Thirdly, in order to study the influence of shaping on mechanical properties, several shapes were created with copolymers yarns: braids, ropes and linear or rolled knitted scaffolds. The rolled knitted scaffold presented interesting mechanical characteristics, similar to native anterior cruciate ligament (ACL) with a 67 MPa Young's Modulus and a stress at failure of 22.5 MPa. These findings suggest that this three dimensional rolled knitted scaffold meet the mechanical properties of ligament tissues and could be suitable as a scaffold for ligament reconstruction. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 735-743, 2017.
Asunto(s)
Ligamento Cruzado Anterior/química , Poloxámero/química , Poliésteres/química , Estrés Mecánico , Andamios del Tejido/química , Animales , Ensayo de Materiales , RatasRESUMEN
Biomaterials for soft tissues regeneration should exhibit sufficient mechanical strength, demonstrating a mechanical behavior similar to natural tissues and should also promote tissues ingrowth. This study was aimed at developing new hybrid patches for ligament tissue regeneration by synergistic incorporation of a knitted structure of degradable polymer fibers to provide mechanical strength and of a biomimetic matrix to help injured tissues regeneration. PLA- Pluronic® (PLA-P) and PLA-Tetronic® (PLA-T) new copolymers were shaped as knitted patches and were associated with collagen I (Coll) and collagen I/chondroitine-sulfate (Coll CS) 3-dimensional matrices. In vitro study using ligamentocytes showed the beneficial effects of CS on ligamentocytes proliferation. Hybrid patches were then subcutaneously implanted in rats for 4 and 12 weeks. Despite degradation, patches retained strength to answer the mechanical physiological needs. Tissue integration capacity was assessed with histological studies. We showed that copolymers, associated with collagen and chondroitin sulfate sponge, exhibited very good tissue integration and allowed neotissue synthesis after 12 weeks in vivo. To conclude, PLA-P/CollCS and PLA-T/CollCS hybrid patches in terms of structure and composition give good hopes for tendon and ligament regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1778-1788, 2017.
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Sulfatos de Condroitina , Colágeno , Ligamentos Articulares/fisiología , Poliésteres , Regeneración/efectos de los fármacos , Animales , Células Cultivadas , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacología , Colágeno/química , Colágeno/farmacología , Ligamentos Articulares/citología , Poliésteres/química , Poliésteres/farmacología , RatasRESUMEN
With the aim to develop biomaterials for temporary medical devices, a series of novel reducible and/or degradable elastomers has been prepared from PLA-b-PEG-b-PLA copolymers photo-crosslinked with diallyl sulfide or pentaerythritol tetrakis(3-mercaptopropionate). Thermal and mechanical properties, including elastic limit and Young modulus, are assessed. Degradation is then evaluated under standard hydrolytic conditions. Reducibility of a selected elastomer is then illustrated using 2-mercaptoethanol or glutathione as reducing agents. The redox-sensitivity of the selected elastomer and the possibility to modulate the degradability are shown. Considering drug-eluting elastomeric devices applications, anti-inflammatory drug ibuprofen loading is illustrated with the two simplest elastomer formulations. A rapid or slow linear release is observed as a function of the low or high molecular weight of the triblock pre-polymers. Finally, the cytocompatibility of the degradable elastomers is assessed with regard to their potential to favor or inhibit L929 murine fibroblasts proliferation as a function of the hydrophilicity/hydrophobicity of the triblock copolymers.
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Materiales Biocompatibles/química , Proliferación Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos/instrumentación , Elastómeros/química , Ibuprofeno/metabolismo , Polietilenglicoles/química , Polímeros/química , Animales , Antiinflamatorios no Esteroideos/metabolismo , Células Cultivadas , Liberación de Fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Hidrólisis , Ensayo de Materiales , Ratones , Oxidación-ReducciónRESUMEN
Medical imaging is a cornerstone of modern medicine. In that context the development of innovative imaging systems combining biomaterials and contrast agents (CAs)/imaging probes (IPs) for improved diagnostic and theranostic applications focuses intense research efforts. In particular, the classical aliphatic (co)polyesters poly(lactide) (PLA), poly(lactide-co-glycolide) (PLGA) and poly(É-caprolactone) (PCL), attract much attention due to their long track record in the medical field. This review aims therefore at providing a state-of-the-art of polyester-based imaging systems. In a first section a rapid description of the various imaging modalities, including magnetic resonance imaging (MRI), optical imaging, computed tomography (CT), ultrasound (US) and radionuclide imaging (SPECT, PET) will be given. Then, the two main strategies used to combine the CAs/IPs and the polyesters will be discussed. In more detail we will first present the strategies relying on CAs/IPs encapsulation in nanoparticles, micelles, dendrimers or capsules. We will then present chemical modifications of polyesters backbones and/or polyester surfaces to yield macromolecular imaging agents. Finally, opportunities offered by these innovative systems will be illustrated with some recent examples in the fields of cell labeling, diagnostic or theranostic applications and medical devices.
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Diagnóstico por Imagen/métodos , Poliésteres , Nanomedicina Teranóstica/métodos , Medios de Contraste , Ácido Láctico , Imagen por Resonancia Magnética , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos XRESUMEN
Cancer vaccines are considered to be a promising tool for cancer immunotherapy. However, a well-designed cancer vaccine should combine a tumor-associated antigen (TAA) with the most effective immunomodulatory agents and/or delivery system to provoke intense immune responses against the TAA. In the present study, we introduced a new approach by conjugating the immunomodulatory molecule LD-indolicidin to the hydrophilic chain end of the polymeric emulsifier poly(ethylene glycol)-polylactide (PEG-PLA), allowing the molecule to be located close to the surface of the resulting emulsion. A peptide/polymer conjugate, named LD-indolicidin-PEG-PLA, was synthesized by conjugation of the amine end-group of LD-indolicidin to the N-hydroxysuccinimide-activated carboxyl end-group of PEG. As an adjuvant for cancer immunotherapeutic use, TAA vaccine candidate formulated with the LD-indolicidin-PEG-PLA-stabilized squalene-in-water emulsion could effectively help to elicit a T helper (Th)1-dominant antigen-specific immune response as well as antitumor ability, using ovalbumin (OVA) protein/EG7 cells as a TAA/tumor cell model. Taken together, these results open up a new approach to the development of immunomodulatory antigen delivery systems for vaccine adjuvants and cancer immunotherapy technologies.
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Antígenos de Neoplasias/inmunología , Sistemas de Liberación de Medicamentos , Inmunidad/efectos de los fármacos , Neoplasias/inmunología , Péptidos/química , Polietilenglicoles/química , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacología , Animales , Antígenos de Neoplasias/química , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Emulsiones , Femenino , Inmunomodulación , Inmunoterapia , Ratones , Ratones Endogámicos C57BL , Neoplasias/tratamiento farmacológico , Ovalbúmina/química , Escualeno/química , Succinimidas/químicaRESUMEN
The treatment of anterior cruciate ligament (ACL) failures remains a current clinical challenge. The present study aims at providing suitable degradable scaffolds for ligament tissue engineering. First, we focus on the design and the evaluation of poly(lactide)/poloxamer or poly(lactide)/poloxamine multiblock copolymers selected and developed to have suitable degradation and mechanical properties to match ACL repair. In the second part, it is shown that the copolymers can be processed in the form of microfibers and scaffolds consisting of a combination of twisted/braided fibers to further modulate the mechanical properties and prepare scaffold prototypes suitable for ligament application. Finally, after assessment of their cytocompatibility, the polymer scaffolds are associated with mesenchymal stem cells (MSCs). MSC differentiation toward a ligament fibroblast phenotype is promoted by a dual stimulation including an inductive culture medium and cyclic mechanical loads. RT-qPCR analyses confirm the potential of our scaffolds and MSCs for ACL regeneration with upregulation of some differentiation markers including Scleraxis, Tenascin-C and Tenomodulin.