Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Colloid Interface Sci ; 569: 57-67, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32105903

RESUMO

Aiming to prepare oily core pH-sensitive nanocapsules (NCs) for anticancer drugs delivery, the use of a dextran-based transurf (DexN3-τCTAγ) as both stabilizer and macromolecular chain transfer agent in methyl methacrylate/2-(diethylamino)ethyl methacrylate (MMA/DEAEMA) miniemulsion copolymerization was investigated. NCs of about 195 nm with an oily-core of Miglyol 810 (M810) and a dextran coverage covalently linked to the poly(MMA-co-DEAEMA) intern shell have been obtained. Compared to the non-sensitive PMMA-based NCs (prepared in a similar way), these novel objects were shown to swell in acidic media and to trigger Coumarin 1 release in physiological relevant pH range. As a starting point of NCs biological effects, cytotoxicity and NCs-proteins interactions studies were performed with both PMMA and poly(MMA-co-DEAEMA)-based NCs. Finally, free azide functions from dextran-based coverage were successfully exploited to attach fluorescent model dyes to NCs surface. The overall results suggest that this novel NCs platform could be potentially used as drug nanocarriers for intravenous injection.

2.
Cells ; 9(1)2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31877663

RESUMO

Tumor necrosis factor receptor 2 (TNFR2) is expressed on some tumor cells, such as myeloma, Hodgkin lymphoma, colon cancer and ovarian cancer, as well as immunosuppressive cells. There is increasingly evidence that TNFR2 expression in cancer microenvironment has significant implications in cancer progression, metastasis and immune evasion. Although nanomedicine has been extensively studied as a carrier of cancer immunotherapeutic agents, no study to date has investigated TNFR2-targeting nanomedicine in cancer treatment. From an epigenetic perspective, previous studies indicate that DNA demethylation might be responsible for high expressions of TNFR2 in cancer models. This perspective review discusses a novel therapeutic strategy based on nanomedicine that has the capacity to target TNFR2 along with inhibition of DNA demethylation. This approach may maximize the anti-cancer potential of nanomedicine-based immunotherapy and, consequently, markedly improve the outcomes of the management of patients with malignancy.

3.
Materials (Basel) ; 12(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547298

RESUMO

From a set of around 100 phosphorus-containing polymers tested in pyrolysis-combustion flow calorimetry, the contributions to flammability of two phosphorus-containing pendant groups (called 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) and PO3) were calculated using an advanced method previously proposed and validated. The flammability properties include total heat release (THR) and heat release capacity (HRC) measured in standard conditions, i.e., anaerobic pyrolysis and complete combustion. The calculated contributions are in good agreement with the main modes of action of both phosphorus groups, i.e., flame inhibition for DOPO and char promotion for PO3. Moreover, the results provide first conclusions about the cooperative interaction between phosphorus and nitrogen, as well as the influence of the architecture of tested co-polymers.

4.
Carbohydr Polym ; 224: 115153, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472862

RESUMO

A multi-reactive polysaccharide-based transurf (acting both as macro-Chain Transfer Agent and stabilizer) was used to confine RAFT polymerization of methyl methacrylate (MMA) at the oil/water (o/w) miniemulsion interface. Dithiobenzoate groups and hydrophobic aliphatic side chains were introduced onto dextran, conferring it both transfer agent properties and ability to stabilize direct miniemulsion of MMA in the presence of a biocompatible oil, used as co-stabilizer. Because of their amphiphilic character, transurfs were initially adsorbed at the (o/w) interface and their reactive sites mediated RAFT polymerization via the R-group approach. PMMA-grafted dextran glycopolymers were consequently produced at the o/w interface, thus leading to dextran coverage/PMMA shell/oily core nanocapsules (NCs) as evidenced by Cryo-TEM analyses. The influence of dextran-based transurf chemistry and oil amount on MMA RAFT polymerization control was investigated. Positive preliminary results on NCs cytotoxicity suggest the potential of these objects for biomedical applications.

5.
Colloids Surf B Biointerfaces ; 182: 110393, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357128

RESUMO

In this work, photo-sensitive core/shell nanoparticles (NPs) based on biocompatible dextran-g-poly(o-nitrobenzyl acrylate) copolymers (Dex-g-PNBA), containing dextran as hydrophilic backbone and PNBA as photosensitive grafts, were formulated using two processes. In the first process (nanoprecipitation), NPs were prepared using preformed Dex-g-PNBA copolymers. Using the second process (emulsion/organic solvent evaporation), "clicked" or "unclicked" NPs were obtained carrying out (or not) an interfacial in situ click chemistry, respectively. Two model molecules, Nile Red (NR) and Doxorubicin (DOX), were encapsulated and their controlled release from NPs was investigated under UV irradiations to demonstrate the high potential of such photosensitive NPs in biomedicine applications as drug delivery nanocarriers. According to such irradiations, improved release was easily observed. Release kinetics depended on the formulation process and the NPs core chemistry, but not on the occurrence of the interfacial in situ click chemistry. More interesting, a stepped release of such model molecules may easily be obtained.


Assuntos
Acrilatos/química , Preparações de Ação Retardada/farmacologia , Dextranos/química , Doxorrubicina/farmacologia , Nanopartículas/química , Polímeros/química , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Química Click , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Liberação Controlada de Fármacos/efeitos da radiação , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/efeitos da radiação , Raios Ultravioleta
6.
J Colloid Interface Sci ; 514: 289-298, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29275247

RESUMO

HYPOTHESIS: For some years, smart nano-objects are one of the main focuses of current research. In the framework of polymeric nanomedicine, o-nitrobenzyl alcohol derivatives lead to light-responsive polymeric materials. At this day, nanomedicine based on polysaccharide/poly(o-nitrobenzyl acrylate) (PNBA) copolymers have never been reported. EXPERIMENTS: For the first time, PNBA core/dextran shell nanoparticles (NPs) were formulated by evaluating two different processes: (i) nanoprecipitation of preformed Dextran-g-PNBA glycopolymers, (ii) emulsion/evaporation using azido-functionalized PNBA and alkynated dextran, carrying out (or not) an interfacial click chemistry reaction. NPs' characterization, colloidal stability in the presence of salts and of an anionic competitive surfactant (SDS) and light-induced disruption were assessed. Finally, the potential use of these NPs as photo-responsive drug delivery systems was investigated by a preliminary in vitro cytotoxicity study using Caco-2 cells. FINDINGS: Whatever the process, the photosensitive property and the colloidal stability of NPs in the presence of salts were proved. However, triazole rings between the dextran shell and the PNBA core avoid the dextran shell desorption in the presence of SDS. NPs' biocompatibility towards Caco-2 was proved and 100% cell viability was still observed after exposure to NPs following by 60 s UV-irradiation.


Assuntos
Dextranos/farmacologia , Sistemas de Liberação de Medicamentos , Luz , Nanopartículas/química , Polissacarídeos/química , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Dextranos/química , Humanos
7.
Colloids Surf B Biointerfaces ; 162: 351-361, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29227921

RESUMO

PLA nanoparticles loaded with n-alkyl gallates (AGs) were prepared either by nanoprecipitation (NP) or by O/W emulsion/solvent evaporation (E/SE). A nonionic hydrophobically modified polysaccharide was used for surface coverage and for ensuring colloidal stability. Different parameters were systematically assessed to enhance the drug incorporation, with the aim of obtaining monomodal and narrow particle size distributions. The nanoparticles were characterized by 1H NMR, transmission electron microscopy (TEM) and laser light scattering granulometry. The colloidal stability of suspensions was evaluated after incubation in NaCl solutions and was maintained up to 1M NaCl. The mean particle diameter and the width of size distribution were found very similar for both processes (slightly lower diameters when using E/SE) with various drug loadings. The amount of encapsulated AG by E/SE was about twice that encapsulated by NP. The in-vitro release of AG was evaluated under sink conditions and no burst effect was observed. Release curves were successfully modeled using the Fick diffusion model with a constant diffusion coefficient and assuming non-swellable particles. Diffusion coefficients of AG loaded in nanoparticles prepared by NP were higher than those found in nanoparticles elaborated by E/SE.


Assuntos
Portadores de Fármacos , Composição de Medicamentos/métodos , Ácido Gálico/análogos & derivados , Nanopartículas/química , Poliésteres/química , Precipitação Química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Emulsões , Ácido Gálico/química , Cinética , Tamanho da Partícula , Cloreto de Sódio/química
8.
J Mech Behav Biomed Mater ; 68: 134-143, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28161663

RESUMO

Alginate-based hydrogel scaffolds are widely used in the field of cartilage regeneration and repair. If the effect of autoclaving on the alginate powder is well known, it is not the same for the possible effects of the sterilization UV treatment on the properties of the hydrogel after polymerization. To select an effective sterilization treatment of alginate-based materials, one must find what are inter-relationship between the characteristics (chemical, physical and mechanical) of alginate-based hydrogel during sterilization, and what consequences have affected on cell behavior. In this study, we investigated the influence of UV sterilization treatments (UV-1 and UV-2: 25 and 50min, respectively) and autoclaving to obtain alginate (Alg)/hyaluronic acid (HA) hydrogel, as well as further evaluated the relationship between physicochemical properties and cell behavior of Alg/HA hydrogel after UVs and autoclaving. The physicochemical properties of this mixture at the powder or polymerized states were analyzed using ATR-FTIR, HPLC-SEC, rheological, indentation testing and sterility testing. The cell behaviors of hydrogels were evaluated by cell viability and proliferation, and chondrogenic differentiation. The effects of treatment parameters and their correlation with the others characteristics were determined statistically by Principal Component Analysis (PCA). In this study, we have shown that the cell behavior in alginate-based hydrogels was not only regulated by physicochemical properties (as molar mass or/and viscosity), but also associated with the controlling of sterilization time. It can provide a basis for choosing an effective method of sterilization, which can keep the mechanical or physical-chemical properties of Alg-based hydrogel scaffold and maintain its cytocompatibility and its ability to induce chondrogenesis from mesenchymal stem cells.


Assuntos
Alginatos/química , Condrogênese , Hidrogéis/química , Células-Tronco Mesenquimais/citologia , Esterilização , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos
9.
Carbohydr Polym ; 136: 598-608, 2016 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-26572392

RESUMO

Among all photosensitive monomers reported in the literature, o-nitrobenzyl acrylate (NBA) was selected in this present study. Two strategies were compared to produce azido-terminated poly(o-nitrobenzyl acrylate) (PNBA) using controlled Single Electron Transfer-Living Radical Polymerization (SET-LRP). In a parallel way, dextran (Dex) was modified by the introduction of several alkynyl-terminated hydrophobic chains. Finally, an Huisgen-type Copper (I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) click-chemistry was carried out to produce amphiphilic Dex-g-PNBA glycopolymers with different number and length of PNBA grafts. 2D DOSY (1)H NMR was used to prove the formation of such glycopolymers. Preliminary study on Dex-g-PNBA self-assembly was done by measuring the critical water content (CWC) above which Dex-g-PNBA started to auto-organize themselves to produce nano-objects. Finally, under UV irradiation, PNBA grafts turn into poly(acrylic acid) ones giving light-sensitive properties to such amphiphilic Dex-g-PNBA. Such properties were evaluated and compared with those of PNBA.


Assuntos
Acrilatos/química , Dextranos/química , Fármacos Fotossensibilizantes/síntese química , Tensoativos/síntese química , Química Click , Nitrobenzenos/química , Fármacos Fotossensibilizantes/química , Tensoativos/química
10.
Pharm Res ; 32(12): 3886-98, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26134451

RESUMO

PURPOSE: Despite the promising applications of PLGA based particles, studies examining the fate and consequences of these particles after intra-articular administration in the joint are scanty. This study was carried out to evaluate the neutrality of the unloaded delivery system on different articular cell types. To facilitate tracking, we have thus developed a fluorescent core of particles, combined to a hyaluronate shell for cell recognition. METHODS: Fluorescence pictures were taken at time intervals to assess the internalization and the corresponding inflammatory response was monitored by RT-qPCR and biochemical measurements. After NPs pre-treatment, mesenchymal stem cells (MSCs) were cultured into chondrogenic, adipogenic or osteogenic differentiation media, to investigate if NPs exposure interferes with differentiation ability. Finally, intra-articular injections were performed in healthy rat knees and joint's structure analysed by histological studies. RESULTS: Particles were detected in cytoplasm 8 h after exposure. Internalization led to a slight and reversible increase of inflammatory markers, but lower than in inflammatory conditions. We have confirmed particles exposure minimal neutrality on MSCs pluripotency. Histological exams of joint after intra-articular injections do not demonstrate any side effects of NPs. CONCLUSIONS: Our findings suggest that such a delivery platform is well tolerated locally and could be used to deliver active molecules to the joint.


Assuntos
Portadores de Fármacos/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Adipogenia , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Condrogênese , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/metabolismo , Humanos , Inflamação/etiologia , Inflamação/patologia , Injeções Intra-Articulares , Articulação do Joelho/ultraestrutura , Ácido Láctico/administração & dosagem , Ácido Láctico/efeitos adversos , Ácido Láctico/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Nanopartículas/administração & dosagem , Nanopartículas/efeitos adversos , Nanopartículas/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Osteogênese , Ácido Poliglicólico/administração & dosagem , Ácido Poliglicólico/efeitos adversos , Ácido Poliglicólico/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Wistar
11.
Carbohydr Polym ; 130: 141-8, 2015 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-26076610

RESUMO

A multi-reactive polysaccharide-based inisurf (acting both as initiator and stabilizer) has been designed for the first time from dextran with the aim of preparing dextran-covered nanoparticles with covalent linkage between core and coverage. This inisurf was used for polymerizing butyl acrylate in miniemulsion by AGET-ATRP. Both hydrophobic phenoxy groups and initiator groups (bromoisobutyryl ester) were introduced within hydrophilic dextran chain, conferring it amphiphilic and macroinitiator characters. Amphiphilic properties of dextran inisurfs have been evidenced as well as their ability to stabilize the direct miniemulsion of n-butyl acrylate. After optimization of polymerization conditions with model studies, assays were successfully realized with dextran-based inisurfs. Because of their amphiphilic character, inisurfs migrated at oil/water interface and initiated polymerization from bromoisobutyryl ester groups. Therefore graft copolymers were produced at oil/water interface, due to the multifunctional character of these inisurfs and constituted the particle inner core with covalent links to the dextran coverage.


Assuntos
Dextranos/química , Emulsões/química , Polimerização , Interações Hidrofóbicas e Hidrofílicas , Cinética , Espectroscopia de Ressonância Magnética , Nanopartículas/química , Propriedades de Superfície , Tensoativos/química
12.
Eur J Pharm Biopharm ; 85(3 Pt A): 640-9, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23954508

RESUMO

S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) were formulated into in situ forming implants (ISI) and microparticles (ISM) using PLGA and either N-methyl-2-pyrrolidone (NMP) or triacetin. Physicochemical characterization was carried out, including the study of matrix structure and degradation. A strong correlation between drug hydrophobicity and the in vitro release profiles was observed: whatever the formulation, GSNO and SNAP were completely released after ca. 1 day and 1 week, respectively. Then, selected formulations (i.e., SNAP-loaded NMP formulations) demonstrated the ability to sustain the vasodilation effect of SNAP, as shown by monitoring the arterial pressure (telemetry) of Wistar rats after subcutaneous injection. Both ISI and ISM injections resulted in a 3-fold extended decrease in pulse arterial pressure compared with the unloaded drug, without significant decrease in the mean arterial pressure. Hence, the results emphasize the suitability of these formulations as drug delivery systems for S-nitrosothiols, widening their therapeutic potential.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , S-Nitroso-N-Acetilpenicilamina/administração & dosagem , S-Nitrosoglutationa/administração & dosagem , Animais , Pressão Arterial/efeitos dos fármacos , Química Farmacêutica , Preparações de Ação Retardada , Implantes de Medicamento , Interações Hidrofóbicas e Hidrofílicas , Ácido Láctico/química , Masculino , Microesferas , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Pirrolidinonas/química , Ratos , Ratos Wistar , S-Nitroso-N-Acetilpenicilamina/química , S-Nitrosoglutationa/química , S-Nitrosoglutationa/farmacologia , Telemetria , Triacetina/química , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Vasodilatadores/química , Vasodilatadores/farmacologia
13.
J Biomater Sci Polym Ed ; 24(8): 899-911, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23647247

RESUMO

This study aims to investigate the in vitro degradation of a poly(L-lactic-co-glycolic acid)-poly(L-lactic-co-ϵ-caprolactone) (PLGA-PLCL) composite scaffold's mechanical properties under static culture condition and 2 h period per day of traction-torsion cyclic culture conditions of simultaneous 10% uniaxial strain and 90° of torsion cycles at 0.33 Hz. Scaffolds were cultured in static conditions, during 28 days, with or without cell seeded or under dynamic conditions during 14 days in a bioreactor. Scaffolds' biocompatibility and proliferation were investigated with Alamar Blue tests and cell nuclei staining. Scaffolds' mechanical properties were tested during degradation by uniaxial traction test. The PLGA-PLCL composite scaffold showed a good cytocompatibility and a high degree of colonization in static conditions. Mechanical tests showed a competition between two process of degradation which have been associated to hydrolytic and enzymatic degradation for the reinforce yarn in poly(L-lactic-co-glycolic acid) (PLGA). The enzymatic degradation led to a decrease effect on mechanical properties of cell-seeded scaffolds during the 21st days, but the hydrolytic degradation was preponderant at day 28. In conclusion, the structure of this scaffold is adapted to culture in terms of biocompatibility and cell orientation (microfiber) but must be improved by delaying the degradation of it reinforce structure in PLGA.


Assuntos
Materiais Biocompatíveis/química , Ácido Láctico/química , Poliésteres/química , Ácido Poliglicólico/química , Tecidos Suporte , Animais , Técnicas de Cultura de Células , Proliferação de Células , Ligamentos , Masculino , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Wistar , Células-Tronco/citologia , Resistência à Tração , Engenharia Tecidual/métodos
14.
Carbohydr Polym ; 93(2): 537-46, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23499094

RESUMO

Dextran-covered PLA nanoparticles have been formulated by two strategies. On one hand, dextran-g-PLA copolymers have been synthesized by click-chemistry between azide-multifunctionalized dextran (DexN3) and alkyne end-functionalized PLA chains (α-alkyne PLA); then nanoprecipitated without any additional surfactants. On the other hand, DexN3 exhibiting surfactant properties have been emulsified with unfunctionalized or α-alkyne PLA, which are dissolved in organic phase with or without CuBr. Depending on the o/w emulsion/evaporation process experimental conditions, dextran-g-PLA copolymers have been produced in situ, by click chemistry at the liquid/liquid interface during the emulsification step. Whatever the process, biodegradable core/shell polymeric nanoparticles have been obtained, then characterized. Colloidal stability of these nanoparticles in the presence of NaCl or SDS has been studied. While the physically adsorbed polysaccharide based shell has been displaced by SDS, the covalently-linked polysaccharide based shell ensures a permanent stability, even in the presence of SDS.

15.
J Biomech Eng ; 133(6): 065001, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21744936

RESUMO

Tissue engineering offers an interesting alternative to current anterior cruciate ligament (ACL) surgeries. Indeed, a tissue-engineered solution could ideally overcome the long-term complications due to actual ACL reconstruction by being gradually replaced by biological tissue. Key requirements concerning the ideal scaffold for ligament tissue engineering are numerous and concern its mechanical properties, biochemical nature, and morphology. This study is aimed at predicting the morphology of a novel scaffold for ligament tissue engineering, based on multilayer braided biodegradable copoly(lactic acid-co-(e-caprolactone)) (PLCL) fibers The process used to create the scaffold is briefly presented, and the degradations of the material before and after the scaffold processing are compared. The process offers varying parameters, such as the number of layers in the scaffold, the pitch length of the braid, and the fibers' diameter. The prediction of the morphology in terms of pore size distribution and pores interconnectivity as a function of these parameters is performed numerically using an original method based on a virtual scaffold. The virtual scaffold geometry and the prediction of pore size distribution are evaluated by comparison with experimental results. The presented process permits creation of a tailorable scaffold for ligament tissue engineering using basic equipment and from minimum amounts of raw material. The virtual scaffold geometry closely mimics the geometry of real scaffolds, and the prediction of the pore size distribution is found to be in good accordance with measurements on real scaffolds. The scaffold offers an interconnected network of pores the sizes of which are adjustable by playing on the process parameters and are able to match the ideal pore size reported for tissue ingrowth. The adjustability of the presented scaffold could permit its application in both classical ACL reconstructions and anatomical double-bundle reconstructions. The precise knowledge of the scaffold morphology using the virtual scaffold will be useful to interpret the activity of cells once it will be seeded into the scaffold. An interesting perspective of the present work is to perform a similar study aiming at predicting the mechanical response of the scaffold according to the same process parameters, by implanting the virtual scaffold into a finite element algorithm.


Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/cirurgia , Engenharia Tecidual , Tecidos Suporte , Ligamento Cruzado Anterior/fisiopatologia , Materiais Biocompatíveis/química , Fenômenos Biomecânicos , Engenharia Biomédica , Simulação por Computador , Humanos , Poliésteres/química , Tecidos Suporte/química , Interface Usuário-Computador
16.
Biomed Mater Eng ; 20(3): 235-42, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20930333

RESUMO

The aim of this study is to evaluate the toxicity of nanoparticles of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co-glycolic acid) (PLGA) covered by chemically esterified amphiphilic hyaluronate (HA) which will be used for intra-articular injection as a drug carrier for the treatment of arthritis (RA) and/or osteoarthritis (OA). PLA and PLGA are FDA approved polymers that are already used for the preparation of nano or microparticles. HA is a natural polysaccharide already present in the articulations known to interact with the CD44 receptors of the cells (especially chondrocytes). Therefore, we can envisage that the HA covering can improve the interactions between the cells and the nanoparticles, leading to better targeting or biodistribution. The knee of healthy male rats was injected one to two times weekly, with various concentrations of nanoparticles encapsulating Dextran-FITC. The synovial membranes and the patellae were collected aseptically and histologically analyzed to assess the effects and localization of the nanocapsules in the knee joint. We did not observe significant modifications in the synovial membranes (weak hyperplasia) or patellae integrity after local administration of nanodevices into the rats. While we found some nanoparticles in the synovial membrane, none were detected in the patellae. Moreover, the histological observations for patellae were confirmed by radiosulfate intake, which depicted no decrease in proteoglycans biosynthesis in nanoparticles treated animals. Concerning the safety towards synovial membranes, we also had a look at the inflammatory response after injections of nanoparticles covered by amphiphilic HA or polyvinyl alcohol (PVA) by monitoring the mRNA expression levels of some specific early cytokines (IL-1ß and TNF-α). Once again, no differences were observed between the control rats and the rats treated with nanoparticles. Considering these preliminary results obtained in healthy rats, we can establish that neither the amphiphilic HA-covered PLGA nanoparticles nor their degradation products induce major modifications of articular tissues functions, while injected into the knee of healthy rats. These results should be confirmed in OA or RA rat models, in order to confirm that nanoparticles do not worsen already altered (degenerative or inflamed) articular tissues. Once confirmed, such tuneable nanoparticles could be proposed as a safe drug delivery system for the treatment of articular disease, allowing a wide range of encapsulating molecules.


Assuntos
Materiais Revestidos Biocompatíveis/administração & dosagem , Portadores de Fármacos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Articulações/efeitos dos fármacos , Articulações/patologia , Ácido Láctico/efeitos adversos , Nanopartículas/administração & dosagem , Ácido Poliglicólico/efeitos adversos , Animais , Materiais Revestidos Biocompatíveis/efeitos adversos , Portadores de Fármacos/efeitos adversos , Ácido Hialurônico/efeitos adversos , Ácido Hialurônico/química , Injeções Intra-Articulares , Ácido Láctico/química , Masculino , Teste de Materiais , Nanopartículas/efeitos adversos , Nanopartículas/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia
17.
J Biomed Mater Res A ; 94(4): 1270-82, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20694995

RESUMO

We developed a novel technique involving knitting and electrospinning to fabricate a composite scaffold for ligament tissue engineering. Knitted structures were coated with poly(L-lactic-co-e-caprolactone) (PLCL) and then placed onto a rotating cylinder and a PLCL solution was electrospun onto the structure. Highly aligned 2-microm-diameter microfibers covered the space between the stitches and adhered to the knitted scaffolds. The stress-strain tensile curves exhibited an initial toe region similar to the tensile behavior of ligaments. Composite scaffolds had an elastic modulus (150 +/- 14 MPa) similar to the modulus of human ligaments. Biological evaluation showed that cells proliferated on the composite scaffolds and they spontaneously orientated along the direction of microfiber alignment. The microfiber architecture also induced a high level of extracellular matrix secretion, which was characterized by immunostaining. We found that cells produced collagen type I and type III, two main components found in ligaments. After 14 days of culture, collagen type III started to form a fibrous network. We fabricated a composite scaffold having the mechanical properties of the knitted structure and the morphological properties of the aligned microfibers. It is difficult to seed a highly macroporous structure with cells, however the technique we developed enabled an easy cell seeding due to presence of the microfiber layer. Therefore, these scaffolds presented attractive properties for a future use in bioreactors for ligament tissue engineering.


Assuntos
Ligamentos/efeitos dos fármacos , Ligamentos/fisiologia , Poliésteres/química , Poliésteres/farmacologia , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/farmacologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Membranas Artificiais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/ultraestrutura , Microscopia Eletrônica de Varredura , Ratos , Ratos Wistar , Resistência à Tração/efeitos dos fármacos
18.
Colloids Surf B Biointerfaces ; 51(1): 86-92, 2006 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-16806853

RESUMO

We have already shown that polylactide (PLA) nanoparticles covered with a hydrophilic polymeric layer can be prepared by simple emulsion/solvent evaporation by using amphiphilic copolymers as surfactants during the procedure. The external layer is then constituted by the hydrophilic part of the macromolecular surfactant. This kind of nanospheres is useful for the encapsulation of lipohilic molecules. The use of amphiphilic copolymers as surfactants in the preparation of PLA nanospheres with controlled surface properties, was then applied to the double emulsion/solvent evaporation procedure. The aim was to allow the encapsulation of water-soluble bioactive molecules in PLA particles with controlled surface properties. In this paper, we describe the results obtained with three different water-soluble monomethoxypolyethylene oxide (MPEO)-b-PLA diblock copolymers used as surfactants in the preparation of nanoparticles by double emulsion/solvent evaporation. After organic solvent evaporation, the obtained nanospheres were proved to be really covered by a MPEO layer whose characteristics were determined. It was firstly shown that the MPEO-covered particles did not flocculate at 25 degrees C, even in 4 M NaCl while suspensions of bare nanospheres were destabilized for a NaCl concentration as low as 0.04 M. On the other hand, the suspensions of MPEO-covered nanoparticles in 0.3 M Na2SO4 were found to be very sensitive to temperature as they flocculated at a temperature lying between 45 and 55 degrees C depending on the MPEO-b-PLA composition. This property was attributed to the fact that MPEO is a polymer with a low critical solution temperature. The concentration of MPEO at the nanoparticle surface was then calculated for the three kinds of particles, from the initial flocculation temperature, and was found to be comparable to the value determined directly.


Assuntos
Materiais Biocompatíveis/química , Ácido Láctico/química , Polímeros/química , Tensoativos/química , Água/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/farmacocinética , Coloides , Emulsões , Ácido Láctico/síntese química , Ácido Láctico/farmacocinética , Nanoestruturas , Poliésteres , Polímeros/síntese química , Polímeros/farmacocinética , Solubilidade , Propriedades de Superfície , Tensão Superficial , Tensoativos/síntese química , Tensoativos/farmacocinética , Volatilização
19.
Biomacromolecules ; 4(5): 1443-50, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12959617

RESUMO

The controlled synthesis of biodegradable copolymers of dextran grafted with aliphatic polyesters first requires the preparation of polysaccharide derivatives soluble in organic solvents. Silylation of dextran can thus lead to such organosoluble derivatives and allows the polymerization of cyclic esters initiated from the nonsilylated OH functions. Silylation of dextran was studied in DMSO by different reactants such as 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in the presence of various catalysts and N,O-bis(trimethylsilyl)acetamide (BSA). According to the silylating agent and the used experimental conditions, it was possible to obtain highly or totally silylated dextrans. In parallel, an investigation of the chemical stability of the dextran chain during silylation was performed. Thus, it was found that, when used at 50 degrees C, HMDS with or without catalysts gives a relatively high silylation yield and does not alter the dextran chain length, whereas at 80 degrees C, dextran degradation was observed. BSA is a very good silylating agent, which allows reaching 100% silylation even at 50 degrees C but provokes the degradation of the polysaccharide chains. The work was completed by a study of the reactivity order of the glucosidic OH functions toward silylation reaction. This order was found to be (OH(2) > OH(4) > OH(3)) as already reported for other reactions. 2D-NMR of highly silylated dextrans demonstrated that they are constituted of both quantitatively silylated glucose units and two types of disilylated ones.


Assuntos
Dextranos/química , Silanos/química , Dimetil Sulfóxido , Espectroscopia de Ressonância Magnética , Estrutura Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA