RESUMO
In this study, microemulsions capable of transforming into nanostructured hexagonal phase gels in vivo upon uptake of biological fluids for naltrexone prolonged release were investigated as a strategy for management of alcohol use disorder (AUD). Microemulsions were prepared using monoolein, tricaprylin, water and propylene glycol; after preliminary characterization, one formulation was selected, which contained 55% of monoolein-tricaprylin (M-55). This microemulsion displayed size below 200 nm and Newtonian rheological behavior. Liquid crystalline gels formed in vitro upon 8 h of contact with water following a second order kinetics. After 120 h, <50% of naltrexone was released in vitro independently on drug loading (5 or 10%). In vivo, gels formed within 24 h of M-55 subcutaneous administration, and persisted locally for over 30 days providing slow release of the fluorescent marker Alexa fluor compared to a solution. Using the conditioned place preference paradigm, a test used to measure drug's rewarding effects, a single dose of M-55 containing 5% naltrexone reduced the time spent in the ethanol-paired compartment by 1.8-fold compared to saline; this effect was similar to that obtained with daily naltrexone injections, demonstrating the formulation efficacy and its ability to reduce dosing frequency. A more robust effect was observed following administration of M-55 containing 10% of naltrexone, which was compatible with aversion. These results support M-55 as a platform for sustained release of drugs that can be further explored for management of AUD to reduce dosing frequency and aid treatment adherence.
Assuntos
Dissuasores de Álcool/administração & dosagem , Alcoolismo/tratamento farmacológico , Desenvolvimento de Medicamentos/métodos , Etanol/administração & dosagem , Naltrexona/administração & dosagem , Nanoestruturas/administração & dosagem , Dissuasores de Álcool/sangue , Dissuasores de Álcool/síntese química , Alcoolismo/sangue , Animais , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Injeções Subcutâneas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Naltrexona/sangue , Naltrexona/síntese química , Nanoestruturas/químicaRESUMO
Florfenicol (FLO) is a broad-spectrum fluorinated antibiotic used for the treatment of bacterial diseases such as bovine respiratory disease (BRD) in cattle. FLO is a poorly soluble drug in aqueous solution, and its encapsulation in various nanovehicles has been reported to be less than 30%. In this context, the use of bovine serum albumin (BSA) as a nanocarrier for FLO is an interesting approach. BSA is a biocompatible, biodegradable, nontoxic, and nonimmunogenic natural protein, allowing the vehiculization of hydrophilic and hydrophobic drugs with a well-tolerated administration. The present work focuses on the fabrication and characterization of florfenicol-loaded BSA (FLO-BSA NPs), incorporation efficiency, and in vitro release pattern. FLO-BSA NPs nanoparticles were successfully obtained by a simple, low-cost and in a few steps method. The physicochemical properties of the obtained nanoparticles such as size (~ 120 nm), polydispersity index (0.04), and zeta potential (approximately - 40 mV) suggest a high colloidal stability and suitable characteristics for drug delivery. The drug loading reveals a high incorporation of florfenicol in the nanoparticles, in which 33.6 molecules of FLO are encapsulated per each molecule of BSA. The in vitro release profile exhibits an initial stage characterized by the burst effect and then a prolonged release of FLO from the albumin matrix, which is compatible with the Higuchi model and which follows a Fickian diffusion. The results together suggest a suitable tool for future investigations in drug delivery field in order to use this nanomaterial in food, pharmaceutical, and veterinary industry.
Assuntos
Antibacterianos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/metabolismo , Soroalbumina Bovina/farmacocinética , Tianfenicol/análogos & derivados , Animais , Antibacterianos/administração & dosagem , Antibacterianos/síntese química , Bovinos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos/tendências , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/síntese química , Tianfenicol/administração & dosagem , Tianfenicol/síntese química , Tianfenicol/farmacocinéticaRESUMO
Arabic gum-based and chitosan-based hydrogels were synthesized through chemical crosslinking for the immobilization and controlled release of bovine serum albumin (BSA) and characterized by Fourier-transform infrared spectrometry, scanning electron microscopy and swelling assays. The degrees of swelling of the Arabic gum-based hydrogel were 13.22 and 22.95â¯g water per g dried hydrogel at pHâ¯4.5 and 7.0, respectively, whereas the degrees of swelling of the chitosan-based hydrogel were 15.32 and 36.10â¯g water per g dried hydrogel, respectively. The water absorption mechanism in both hydrogels was non-Fickian, which involves diffusion through pores and macromolecular relaxation of the hydrophilic three-dimensional polymer network. BSA immobilization capacities of the Arabic gum-based and chitosan-based hydrogels after 240â¯min at pHâ¯4.5 were 71.0 and 175.6â¯mg protein per g dried hydrogel, respectively. BSA immobilization capacities after 240â¯min at pHâ¯7.0 were 62.5 and 154.2â¯mg protein per g dried hydrogel, respectively. The controlled release of BSA from the Arabic gum-based hydrogel was slightly more efficient than that of the chitosan-based hydrogel due to its more porous structure and weaker physiochemical interactions between the polymer network and protein molecule. Both hydrogels could be employed as carriers of proteins and as capsules for food supplements.
Assuntos
Quitosana/química , Preparações de Ação Retardada/química , Glicoconjugados/química , Goma Arábica/química , Hidrogéis/química , Soroalbumina Bovina/química , Acrilamida/química , Acrilamidas/química , Acrilatos/química , Animais , Bovinos , Reagentes de Ligações Cruzadas/química , Preparações de Ação Retardada/síntese química , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Hidrogéis/síntese química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Porosidade , MolhabilidadeRESUMO
Several authors have studied the release profile of drugs incorporated in different devices. However, to the best of our knowledge, although many studies have been done on the release of tetracycline, in these release devices, no study has investigated if the released compound is actually the tetracycline, or, instead, a degraded product. This approach is exploited here. In this work, we analyse the influence of two drying methods on the tetracycline delivery behaviour of synthesised glasses using the sol-gel process. We compare the drying methods results using both theoretical models and practical essays, and analyse the chemical characteristic of the released product in order to verify if it remains tetracycline. Samples were freeze-dried or dried in an oven at 37°C and characterised by several methods such as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TG), differential thermogravimetric analysis (DTG), differential thermal analyses (DTA) and gas adsorption analysis (BET). The released concentration of tetracycline hydrochloride was studied as a function of time, and it was measured by ultraviolet spectrophotometry in the tetracycline wavelength. The drug delivery profiles were reasonably consistent with a diffusion model analysis. In addition, we observed higher release rates for the freeze-dried compared to those dried in an oven at 37°C. This higher release can be attributed to larger pore size for the freeze-dried sample systems with tetracycline, which promoted more water penetration, improving the drug diffusion. The analysis of the solution obtained in the release tests using high-performance liquid chromatography- mass spectrometry (HPLC-MS) confirmed that tetracycline was being released.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Tetraciclinas/síntese química , Antibacterianos/administração & dosagem , Antibacterianos/síntese química , Antibacterianos/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Difusão , Composição de Medicamentos/métodos , Liofilização/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Tetraciclinas/administração & dosagem , Tetraciclinas/farmacocinéticaRESUMO
The development of systems for the controlled release of drugs is important because they allow the control of drug absorption and tissue distribution and also can reduce local toxicity. This study aimed to assemble and characterize two types of release systems, consisting of layer-by-layer films obtained from poly(allylamine) hydrochloride with chlorophyll (PAH/CHL films) or chlorophyll incorporated into dipalmitoylphosphatidylcholine liposomes (PAH/Lip+CHL films). For these systems, the molecular aggregation, growth process, thermally stimulated desorption, wettability, and controlling release of CHL was studied by using UV-vis spectroscopy and wetting contact angle analysis. In addition, experiments of photodynamic inactivation using PAH/CHL or PAH/Lip+CHL films with a 633-nm laser light were performed and the susceptibility of Candida albicans (C. albicans) to this approach was examined. Fluorescence and atomic force microscopies were used to investigate the surface morphology after the application of the photoinactivation procedure. A redshift of the UV-vis spectrum associated to films when compared with the spectrum of the CHL solution indicated a molecular aggregation of CHL molecules in the films. The film growth process was determined by a nucleation and a growth of spheroids or rods for either PAH/Lip+CHL or PAH/CHL films, respectively. Thermally activated desorption experiments indicated that interactions between CHL and PAH (126kJ/mol) in PAH/CHL or between Lip+CHL and PAH (140kJ/mol) in PAH/Lip+CHL films may be governed by electrostatic interactions. The wettability of PAH/Lip+CHL films was larger than that for PAH/CHL films, which can be attributed to hydrophilic groups on the surface of the DPPC liposomes. Release experiments revealed that free CHL in PAH/CHL films was released more slowly than its partner incorporated into liposomes. After the photodynamic inactivation, results of survival fraction and fluorescence microscopy revealed that C. albicans presented similar susceptibility for the two kinds of films. AFM supported the fluorescence one suggesting that cell death of C. albicans may occur due to damages to its cell wall by C. albicans.
Assuntos
Candida albicans/efeitos dos fármacos , Clorofila/química , Preparações de Ação Retardada/síntese química , Lipossomos/síntese química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Candida albicans/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Composição de Medicamentos/métodos , Quimioterapia Combinada/métodosRESUMO
A series of thermoresponsive copolymers based on chitosan-g-poly(N-vinylcaprolactam) were synthesized by amidation reaction using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride as coupling reagent. The effect of molecular architecture on the thermoresponsive properties of the graft copolymers solutions was studied by varying the chain length of the grafted poly(N-vinylcaprolactam), PVCL, (in the range from 4 to 26 kDa) and the spacing between grafted chains onto the chitosan backbone. The most interesting characteristic of these copolymers is their solubility in water at temperatures below their lower critical solution temperature (LCST). These solutions presented a LCST between 36 and 44 °C, which decreases with the spacing and length of grafted PVCL chains onto the chitosan backbone, in contrast with the limited decrease of the LCST of PVCL above a critical M¯n value around 18 kDa. This behavior offers tangible possibilities for the preparation and application of sensitive bioactive formulations and "smart" drug delivery systems.
Assuntos
Caprolactama/análogos & derivados , Quitosana/análogos & derivados , Preparações de Ação Retardada/química , Polímeros/química , Caprolactama/síntese química , Caprolactama/química , Quitosana/síntese química , Preparações de Ação Retardada/síntese química , Concentração de Íons de Hidrogênio , Morfolinas/síntese química , Morfolinas/química , Polímeros/síntese química , Solubilidade , Temperatura , Água/químicaRESUMO
BACKGROUND: Photodynamic therapy (PDT) is an emerging treatment that has demonstrated potential for the clinical treatment of buccal cancer. It is based on the photoactivation of a photosensitizer (PS) when irradiated by light at a specific wavelength. The light-excited PS generates reactive oxygen species that cause the destruction of tumor cells by apoptosis or necrosis. Toluidine Blue O (TBO) is a PS that has shown potential for PDT in cancer treatment. However, saliva and mechanical activities quickly remove the PS from the surface of the buccal mucosa. Therefore, the bioavailability of PS at the surface of target tissues is reduced. The aim of this study was to evaluate the potential of chitosan (CH) gels in TBO delivery to buccal tissue. METHODS: CH gels were obtained at different concentrations and their physico-chemical properties (pH and rheology), mucoadhesion, in vitro release profile, in vivo retention and in vivo efficacy by the ability to induce cell apoptosis were evaluated. RESULTS: CH-based mucoadhesive gels optimized the release and adherence of preparations at the target site. Specifically, 4% (w/w) CH gel showed adequate properties for buccal use, such as pH value, mucoadhesion, pseudoplastic behavior, extended release, minimal permeation and higher TBO retention by the mucosa. In vivo studies showed the potential of the gel to enhance TBO retention and induce cell apoptosis after laser irradiation. CONCLUSION: 4% (w/w) CH based mucoadhesive gel can be explored as a TBO delivery system in the PDT of oral cancer.
Assuntos
Quitosana/química , Preparações de Ação Retardada/administração & dosagem , Géis/química , Neoplasias Bucais/tratamento farmacológico , Fotoquimioterapia/métodos , Cloreto de Tolônio/administração & dosagem , Absorção Fisico-Química , Administração Oral , Animais , Preparações de Ação Retardada/síntese química , Difusão , Feminino , Camundongos , Neoplasias Bucais/patologia , Fármacos Fotossensibilizantes/administração & dosagem , Cloreto de Tolônio/química , Resultado do Tratamento , ViscosidadeRESUMO
The mesoporous SBA-15 silica with uniform hexagonal pore, narrow pore size distribution and tuneable pore diameter was organofunctionalized with glutaraldehyde-bridged silylating agent. The precursor and its derivative silicas were ibuprofen-loaded for controlled delivery in simulated biological fluids. The synthesized silicas were characterized by elemental analysis, infrared spectroscopy, (13)C and (29)Si solid state NMR spectroscopy, nitrogen adsorption, X-ray diffractometry, thermogravimetry and scanning electron microscopy. Surface functionalization with amine containing bridged hydrophobic structure resulted in significantly decreased surface area from 802.4 to 63.0 m(2) g(-1) and pore diameter 8.0-6.0 nm, which ultimately increased the drug-loading capacity from 18.0% up to 28.3% and a very slow release rate of ibuprofen over the period of 72.5h. The in vitro drug release demonstrated that SBA-15 presented the fastest release from 25% to 27% and SBA-15GA gave near 10% of drug release in all fluids during 72.5 h. The Korsmeyer-Peppas model better fits the release data with the Fickian diffusion mechanism and zero order kinetics for synthesized mesoporous silicas. Both pore sizes and hydrophobicity influenced the rate of the release process, indicating that the chemically modified silica can be suggested to design formulation of slow and constant release over a defined period, to avoid repeated administration.
Assuntos
Anti-Inflamatórios não Esteroides/química , Reagentes de Ligações Cruzadas/química , Preparações de Ação Retardada/síntese química , Glutaral/química , Ibuprofeno/química , Dióxido de Silício/química , Difusão , Composição de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Cinética , Tamanho da Partícula , Porosidade , Propilaminas , Silanos/química , Propriedades de SuperfícieRESUMO
In this work, we synthesized a novel series of hydrogels composed of polyacrylamide (PAAm), methylcellulose (MC), and calcic montmorillonite (MMt) appropriate for the controlled release of fertilizers, where the components presented a synergistic effect, giving very high fertilizer loading in their structure. The synthesized hydrogel was characterized in relation to morphological, hydrophilic, spectroscopic, structural, thermal, and kinetic properties. After those characterizations, the application potential was verified through sorption and desorption studies of a nitrogenated fertilizer, urea (CO(NH2)2). The swelling degree results showed that the clay loading considerably reduces the water absorption capability; however, the hydrolysis process favored the urea adsorption in the hydrogel nanocomposites, increasing the load content according to the increase of the clay mass. The FTIR spectra indicated that there was incorporation of the clay with the polymeric matrix of the hydrogel and that incorporation increased the water absorption speed (indicated by the kinetic constant k). By an X-ray diffraction technique, good nanodispersion (intercalation) and exfoliation of the clay platelets in the hydrogel matrix were observed. Furthermore, the presence of the montmorillonite in the hydrogel caused the system to liberate the nutrient in a more controlled manner than that with the neat hydrogel in different pH ranges. In conclusion, excellent results were obtained for the controlled desorption of urea, highlighting the hydrolyzed hydrogels containing 50% calcic montmorillonite. This system presented the best desorption results, releasing larger amounts of nutrient and almost 200 times slower than pure urea, i.e., without hydrogel. The total values of nutrients present in the system show that this material is potentially viable for application in agriculture as a nutrient carrier vehicle.
Assuntos
Resinas Acrílicas/química , Bentonita/química , Preparações de Ação Retardada/química , Fertilizantes/análise , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Metilcelulose/química , Nanocompostos/química , Resinas Acrílicas/síntese química , Preparações de Ação Retardada/síntese química , Hidrólise , CinéticaRESUMO
N-trimethyl chitosan of two quaternization degrees, DQ=20 and 80mol% and labeled as TMC20 and TMC80, were synthesized and characterized by (1)H NMR. Polyelectrolyte complexes (PECs) of TMC/alginate (TMC/ALG) were prepared at pHs 2, 7 and 10 by mixing the aqueous solutions of unlike polymers. The PECs were characterized through infrared spectroscopy (FTIR), thermogravimetric analysis (TGA/DTG) and wide-angle X-ray scattering (WAXS). Using the TMC of DQ=20 mol% and following the same methodology for preparing the PECs, beads of TMC20/ALG were obtained at pH 2 and loaded with curcumin (CUR) at pH 6.0-6.5. The morphology of the beads was evaluated by scanning electron microscopy (SEM). Studies in vitro of the controlled release of CUR from beads were investigated in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) and treated using conventional and partition-diffusion models. Results indicated that the beads based on TMC20 and ALG presented potential as drug-carrier to improve the solubility and biological activity of CUR at pH close to physiological one.