RESUMO
Nanoparticles made of metal-organic frameworks (nanoMOFs) attract a growing interest in gas storage, separation, catalysis, sensing and more recently, biomedicine. Achieving stable, versatile coatings on highly porous nanoMOFs without altering their ability to adsorb molecules of interest represents today a major challenge. Here we bring the proof of concept that the outer surface of porous nanoMOFs can be specifically functionalized in a rapid, biofriendly and non-covalent manner, leading to stable and versatile coatings. Cyclodextrin molecules bearing strong iron complexing groups (phosphates) were firmly anchored to the nanoMOFs' surface, within only a few minutes, simply by incubation with aqueous nanoMOF suspensions. The coating procedure did not affect the nanoMOF porosity, crystallinity, adsorption and release abilities. The stable cyclodextrin-based coating was further functionalized with: i) targeting moieties to increase the nanoMOF interaction with specific receptors and ii) poly(ethylene glycol) chains to escape the immune system. These results pave the way towards the design of surface-engineered nanoMOFs of interest for applications in the field of targeted drug delivery, catalysis, separation and sensing.
Assuntos
Materiais Revestidos Biocompatíveis/química , Teste de Materiais , Nanopartículas/química , Animais , Linhagem Celular , Camundongos , PorosidadeRESUMO
This study aims to investigate the rheological properties of self-assembling gels containing cyclodextrins with potential application as injectable matrix for the sustained delivery of poorly soluble drugs. The ability of these gels to entrap two hydrophobic molecules, benzophenone (BZ) and tamoxifen (TM), and to allow their in vitro sustained release was evaluated. In view of their future pharmaceutical use, gels were sterilized by high hydrostatic pressures (HHP) and tested for their biocompatibility. The gels formed instantaneously at room temperature, by mixing the aqueous solutions of two polymers: a beta-cyclodextrin polymer (pbetaCD) and a hydrophobically modified dextran by grafting alkyl side chains (MD). MD-pbetaCD gels presented a viscoelastic behavior under low shear, characterized by constant values of the loss modulus G'' and the storage modulus G'. The most stable gels were obtained for a total polymer concentration C(p) of 6.6% and 7.5% (w/w), and a polymer ratio MD/pbetaCD of 50/50 and 33/67 (w/w). BZ and TM were successfully incorporated into MD-pbetaCD gels with loading efficiencies as high as 90%. In vitro, TM and BZ were released gradually from the gel matrix with less than 25% and 75% release, respectively, after 6 days incubation. HHP treatment did not modify the rheological characteristics of MD-pbetaCD gels. Moreover, the low toxicity of these gels after intramuscular administration in rabbits makes them promising injectable devices for local delivery of drugs.
Assuntos
Benzofenonas/farmacologia , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Tamoxifeno/farmacologia , beta-Ciclodextrinas/química , Animais , Materiais Biocompatíveis/metabolismo , Fenômenos Biomecânicos , Dextranos/química , Interações Hidrofóbicas e Hidrofílicas , Pressão Hidrostática , Teste de Materiais , Microscopia Eletrônica de Transmissão , Proteínas/farmacologia , Coelhos , Reologia , Sais/farmacologia , Pele/citologiaRESUMO
The stability of new supramolecular nanoassemblies (nanogels), based on the association of a hydrophobically modified dextran (MD) and a beta-cyclodextrin polymer (pbetaCD), has been studied by two complementary methods: (i) size measurements and (ii) turbidity experiments using a Turbiscan optical analyser. Nanogels of about 120-150nm were obtained whatever the concentration of the two polymer solutions. At low concentrations, the suspensions presented little mean diameter variations upon storage. However, the concentrated ones tended to destabilize and their mean diameter increased upon time. Size measurements and Turbiscan investigations have demonstrated that destabilization in the MD-pbetaCD nanogel suspension was only due to particle aggregation and/or fusion, as no sedimentation or creaming occurred. The destabilization of MD-pbetaCD suspensions led to the formation of a highly viscous phase, as a final state. Moreover, the two methods have shown that aggregation and/or fusion phenomena were more pronounced in the concentrated MD-pbetaCD suspensions than in the diluted ones. The stability of MD-pbetaCD suspensions could be improved by their storage at 4 degrees C. Finally, freeze-drying was found to be a convenient method for the long-time storage of MD-pbetaCD nanoassemblies.
Assuntos
Dextranos/química , Portadores de Fármacos , Liofilização , Polietilenoglicóis , Polietilenoimina , Tecnologia Farmacêutica , beta-Ciclodextrinas/química , Nanogéis , Nefelometria e Turbidimetria/instrumentação , Tamanho da Partícula , Temperatura , Fatores de Tempo , ViscosidadeRESUMO
New nanoassemblies were instantaneously prepared by mixing two aqueous solutions, one containing a beta-cyclodextrin polymer (pbetaCD), and the other a hydrophobically modified by alkyl chains dextran (MD). The formation mechanism and the inner structure of these nanoassemblies were analysed using surface tension measurements and (1)H NMR spectroscopy. The effect of a hydrophobic guest molecule, such as benzophenone (BZ), on the formation and stability of the nanoassemblies was also evaluated. MD exhibited the typical behaviour of a soluble amphiphilic molecule and adsorbed at the air/water interface. Whereas the injection of native beta-CDs in the solution beneath the adsorbed MD monolayer did not produce any change in the surface tension, that of the pbetaCD resulted in an increase in the surface tension, indicating the desorption of the polymer from the interface. This result accounts for a cooperative effect of beta-CDs linked together in the pbetaCD polymer on dextran desorption. The presence of benzophenone in the system hindered the sequestration of dextran alkyl moieties by beta-CD in the polymer without impeding the formation of associative nanoassemblies of 100-200 nm. (1)H NMR investigations demonstrated that, in the BZ-loaded nanoassemblies, the hydrophobic molecule was mainly located into the cyclodextrin cavities.