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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.
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.

3.
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
4.
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
5.
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
6.
J Control Release ; 172(1): 292-304, 2013 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-24001947

RESUMO

In situ forming implants (ISI) based on phase separation by solvent exchange represent an attractive alternative to conventional preformed implants and microparticles for parenteral applications. They are indeed easier to manufacture and their administration does not require surgery, therefore improving patient compliance. They consist of polymeric solutions precipitating at the site of injection and thus forming a drug eluting depot. Drug release from ISI is typically divided into three phases: burst during precipitation of the depot, diffusion of drug through the polymeric matrix and finally drug release by system degradation. This review gives a comprehensive overview on (i) the theoretical bases of these three phases, (ii) the parameters influencing them and (iii) the remaining drawbacks which have to be addressed to enlarge their commercial opportunities. Indeed, although some of them are already commercialized, ISI still suffer from limitations: mainly lack of reproducibility in depot shape, burst during solidification and potential toxicity. Nevertheless, depending on the targeted therapeutic application, these shortcomings may be transformed into advantages. As a result, keys are given in order to tailor these formulations in view of the desired application so that ISI could gain further clinical importance in the following years.


Assuntos
Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Ácido Láctico/química , Preparações Farmacêuticas/administração & dosagem , Ácido Poliglicólico/química , Animais , Humanos , Transição de Fase , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Próteses e Implantes
7.
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
8.
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.

9.
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
10.
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
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