RESUMO
Diosgenin, two synthetic analogs of brassinosteroids, testosterone and dl-α-tocopherol were covalently linked to synthetic water-soluble N,O6-partially acetylated chitosan, for their controlled release. Drug linking was confirmed by FTIR spectroscopy and proton NMR. Conjugates were also characterized by differential scanning calorimetry and wide-angle X-ray diffraction. These conjugates formed self-assembled nanoparticles in aqueous solution with particle sizes ranging from 197 to 358 nm and drug contents between 11.8 and 56.4% (w/w). Spherical 30-60 nm nanoparticles were observed by scanning electron microscopy and transmission electron microscopy upon drying. In vitro release studies performed at acid pH indicated a drug release dependence on substitution degree and particle sizes. Almost constant release rates were observed during the first 6-8h. Brassinosteroids-modified nanoparticles showed good agrochemical activity in radish seeds bioassay at 10(-1) to 10(-4) mg mL(-1). Tocopheryl-modified nanoparticles exhibited radical scavenging activity in DPPH test.
Assuntos
Brassinosteroides/química , Quitosana/química , Portadores de Fármacos/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Tocoferóis/química , Acetilação , Compostos de Bifenilo/química , Brassinosteroides/farmacologia , Preparações de Ação Retardada , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Picratos/química , Reguladores de Crescimento de Plantas/química , Reguladores de Crescimento de Plantas/farmacologia , Raphanus/efeitos dos fármacos , Raphanus/crescimento & desenvolvimento , Tocoferóis/farmacologiaRESUMO
Synthetic O6-succinylated chitosan and commercial glycol chitosan were covalently linked to dl-α-tocopheryl monoesters for controlled release of vitamin E. These conjugates formed self-assembled nanoparticles in aqueous solution with 254-496 nm mean diameters and dl-α-tocopherol contents between 27 and 39% (w/w). The particles appeared as 40-75 nm almost spherical nanoparticles when studied by scanning and transmission electron microscopy upon drying. Drug linking to chitosan matrix was confirmed by FTIR spectroscopy and proton NMR. Conjugates were also characterized by differential scanning calorimetry and wide-angle X-ray diffraction. In vitro tocopherol release studies performed in water at acid pH indicated a drug release dependence on drug content, hydrated particle sizes and employed chitosan derivative. Almost constant release rates were observed the first 7h. The obtained nanoparticles exhibited radical scavenging activity in DPPH essay. The potential of these nanoparticles was also demonstrated by the enhancement of HMVEC cell proliferation.
Assuntos
Quitosana/química , Nanopartículas , alfa-Tocoferol , Quitosana/administração & dosagem , Quitosana/análogos & derivados , Quitosana/síntese química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Células HeLa/efeitos dos fármacos , Humanos , Células MCF-7/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Transmissão , Nanopartículas/administração & dosagem , Nanopartículas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Água/química , alfa-Tocoferol/administração & dosagem , alfa-Tocoferol/químicaRESUMO
Chitosan, alpha-(1-4)-amino-2-deoxy-beta-D-glucan, is a deacetylated form of chitin, an abundant natural polysaccharide present in crustacean shells. Its unique characteristics such as positive charge, biodegradability, biocompatibility, nontoxicity, and rigid linear molecular structure make this macromolecule ideal as drug carrier. The association between chitosan and liposomes was carefully described, where REVs (reverse phase evaporation vesicles) were sandwiched by chitosan. The usage of these particles in vaccine formulation is here proposed for the first time in the literature. The Chitosan-REVs now stabilized by polyvinilic alcohol were the vehicle for Diphtheria toxoid (Dtxd). Round chitosan-sandwiched REVs (REVs-Chi) particles of 373 +/- 17 nm containing 65% Dtxd were obtained. After 200 min of incubation in a simulated gastric fluid, 70% of the Dtxd was liberated from REVs-Chi in comparison to 100% of Dtxd liberated from pure REVs. In PBS, the Dtxd liberation from REVS-Chi was about 60%. Mice were immunized with Dtxd encapsulated within REVs-Chi and with other REVs/Dtxd formulations adsorbed onto Freund adjuvant or alumen [AIF and Al(OH)(3)]. The response patterns and the immune maturity were measured by IgG(1) and IgG(2a) titrations. REVs-Chi containing Dtxd elicited both antibodies production giving the animals higher immune response and selectivity. It was interesting that the memory of those mice immunized with REVs-Chi containing Dtxd enhanced, after booster, antibody production by 47% in contrast with 17 and 7% in mice immunized with the antigen vehiculated in REVs-AIF or REVs-Al(OH)(3), respectively.