RESUMEN
The association of doxorubicin (DOX) and artemisinin (ART) to a ß-CyD-epichlorohydrin crosslinked polymer (pß-CyD), organized in nanoparticles of ca. 15 nm size, was investigated in neutral aqueous medium by circular dichroism (CD), UV-vis absorption and fluorescence. The stability constants and the absolute CD spectra of the drug complexes were determined by global analysis of multiwavelength data from spectroscopic titrations. The polymer pß-CyD proved able to disrupt the DOX dimer when the latter is the predominant form of DOX in solution. The spectroscopic and photophysical properties of the complexes evidenced an alcohol-like environment for ART and an improved inherent emission ability for DOX in the nanoparticle frame.
Asunto(s)
Artemisininas/química , Doxorrubicina/química , Portadores de Fármacos/química , Nanopartículas/química , Análisis Espectral , beta-Ciclodextrinas/química , Epiclorhidrina/química , Modelos Moleculares , Conformación Molecular , Tamaño de la PartículaRESUMEN
The entrapment of two hydrophobic molecules, benzophenone and tamoxifen, into self-assembling cyclodextrin (CD)-based nanogels has been studied. These nanogels formed spontaneously upon the association of a hydrophobically modified dextran (MD) and a cyclodextrin polymer (pbetaCD). The interactions of benzophenone and tamoxifen with MD and pbetaCD were investigated using phase solubility studies, circular dichroism, and isothermal titration calorimetry. Both hydrophobic molecules were included into the CD cavities of the pbetaCD and were also solubilized by MD into its hydrophobic microdomains. We took advantage of these interactions to form benzophenone- and tamoxifen-loaded nanogels. The highest benzophenone loadings were obtained by solubilizing it in both pbetaCD and MD solutions before mixing them to form nanogels. These studies open new possibilities of applications of the nanogels, mainly in the cosmetic field, as sun screen carriers prepared by a simple "green" technology.
Asunto(s)
Benzofenonas/química , Dextranos/química , Polietilenglicoles/química , Polietileneimina/química , Tamoxifeno/química , beta-Ciclodextrinas/química , Interacciones Hidrofóbicas e Hidrofílicas , Nanogeles , SolubilidadRESUMEN
Macromolecular assemblies were elaborated by mixing in water hydrophobically modified dextrans (MDC(n)) and beta-cyclodextrin polymers (pbetaCD) interacting by inclusion complexation between the hydrophobic moieties of MDCn and the beta-cyclodextrin cavities of pbetaCD. Dextrans have been modified by grafting alkyl groups (C(n)) of varying chain lengths (n = 8-16) and grafting ratio (3-6 mol%). Different pbetaCD polymers were synthesized by polycondensation of beta-cyclodextrin and epichlorohydrin. The polymer-polymer interactions have been studied by fluorimetry, isothermal titration microcalorimetry, phase diagrams, and viscosimetry. The viscoelastic properties of the temporary networks (in the semidilute range) have been studied by rheology. The interaction mechanisms between the MDCn and pbetaCD can be understood taking into account the strength of the interaction between the alkyl group and the beta-cyclodextrin cavity (mainly controlled by the alkyl chain length), the density of junctions between the chains (depending on the alkyl grafting density and the pbetaCD molecular weight), and additional cooperative effect (arising for high alkyl grafting density).
Asunto(s)
Polisacáridos/química , beta-Ciclodextrinas/química , Alquilación , Interacciones Hidrofóbicas e Hidrofílicas , Viscosidad , AguaRESUMEN
We show here, for the first time, that two neutral polymers may completely associate together in water to spontaneously form supramolecular nanoassemblies (nanogels) of spherical shape. The cohesion of these stable structures of about 200 nm is based upon a "lock and key" mechanism: inclusion complexes are formed between the hydrophobic alkyl chains grafted on a polysaccharide (dextran) and the molecular cavities contained in a poly-cyclodextrin polymer. Production yields reached 95%. It was established that all the alkyl chains were included within the cyclodextrins' cavities in these nanoassemblies. The multivalent character of the interactions between the two polymers ensures the stability of the nanoassemblies. Moreover, empty cyclodextrin units remained accessible for the inclusion of compounds of interest such as benzophenon or tamoxifen.