RESUMO
Primaquine is the mainstream antimalarial drug to prevent Plasmodium vivax relapses. However, this drug can induce hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Nanostructure formulations of primaquine loaded with D-galactose were used as a strategy to target the drug to the liver and decrease the hemolytic risks. Nanoemulsion (NE-Pq) and nanochitosan (NQ-Pq) formulations of primaquine diphosphate containing D-galactose were prepared and characterized by their physicochemistry properties. Pharmacokinetic and biodistribution studies were conducted using Swiss Webster mice. A single dose of 10 mg/kg of each nanoformulation or free primaquine solution was administered by gavage to the animals, which were killed at 0.5, 1, 2, 4, 8, and 24 hours. Blood samples and tissues were collected, processed, and analyzed by high-performance liquid chromatography. The nanoformulation showed sizes around 200 nm (NE-Pq) and 400 nm (NQ-Pq) and physicochemical stability for over 30 days. Free primaquine solution achieved higher primaquine Cmax in the liver than NE-Pq or NQ-Pq at 0.5 hours. However, the half-life and mean residence time (MRT) of primaquine in the liver were three times higher with the NQ-Pq formulation than with free primaquine, and the volume distribution was four times higher. Conversely, primaquine's half-life, MRT, and volume distribution in the plasma were lower for NQ-Pq than for free primaquine. NE-Pq, on the other hand, accumulated more in the lungs but not in the liver. Galactose-coated primaquine nanochitosan formulation showed increased drug targeting to the liver compared to free primaquine and may represent a promising strategy for a more efficient and safer radical cure for vivax malaria.
Assuntos
Antimaláricos , Quitosana , Galactose , Fígado , Primaquina , Primaquina/farmacocinética , Primaquina/química , Animais , Camundongos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Galactose/química , Quitosana/química , Antimaláricos/farmacocinética , Nanopartículas/química , Distribuição Tecidual , Nanoestruturas/química , MasculinoRESUMO
This study evaluated the photoinactivation of Candida albicans in a murine model of oral candidiasis using chloro-aluminum phthalocyanine (ClAlP) encapsulated in cationic nanoemulsions (NE) and chloro-aluminum phthalocyanine (ClAlP) diluted in DMSO (DMSO) as photosensitizer (PS). Seventy-five 6-week-old female Swiss mice were immunosuppressed and inoculated with C. albicans to induce oral candidiasis. PDT was performed on the tongue by the application of the photosensitizers and LED light (100 J cm(-2) -660 nm). Twenty-four hours and 7 days after treatments, microbiological evaluation was carried out by recovering C. albicans from the tongue of animals (CFU ml(-1) ). Then, mice were sacrificed and the tongues were surgically removed for histological and biomolecular analysis of pro- and anti-inflammatory cytokines. Data were analyzed by ANOVA followed by Tukey's post hoc test. ClAlP-NE-mediated PDT reduced 2.26 log10 of C. albicans recovered from the tongue when compared with the control group (P-L-) (P < 0.05). PDT did not promote adverse effects on the tongue tissue. Seven days after treatment, all animals were completely healthy. In summary, PDT mediated by chloro-aluminum phthalocyanine entrapped in cationic nanoemulsions was effective in reducing C. albicans recovered from the oral lesions of immunocompromised mice.
Assuntos
Candida albicans/efeitos dos fármacos , Candida albicans/efeitos da radiação , Candidíase Bucal/tratamento farmacológico , Indóis/farmacologia , Compostos Organometálicos/farmacologia , Fotoquimioterapia/métodos , Animais , Candida albicans/isolamento & purificação , Candidíase Bucal/microbiologia , Citocinas/análise , Citocinas/genética , Modelos Animais de Doenças , Feminino , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Distribuição Aleatória , Tetraciclina/farmacologia , Língua/efeitos dos fármacos , Língua/microbiologia , Língua/efeitos da radiaçãoRESUMO
The development of biocompatible polymeric nanoparticles has become an important strategy for optimizing the therapeutic efficacy of many classical drugs, as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. In this study, nanoparticles of Amphotericin B entrapped within poly (lactic-co-glycolic) acid and incorporated with dimercaptosuccinic acid (NANO-D-AMB) as a target molecule were evaluated for their physic-chemical characteristics, pharmacokinetics, biocompatibility and antifungal activity. We found high plasma concentrations of Amphotericin B upon treatment with NANO-D-AMB and a high uptake of nanoparticles in the lungs, liver and spleen. NANO-D-AMB exhibited antifungal efficacy against Paracoccidioides brasiliensis and induced much lower cytotoxicity levels compared to D-AMB formulation in vivo and in vitro. Together, these results confirm that NANO-D-AMB improves Amphotericin B delivery and suggest this delivery system as a potential alternative to the use of Amphotericin B sodium deoxycholate.
Assuntos
Anfotericina B/química , Anfotericina B/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Ácido Desoxicólico/química , Ácido Desoxicólico/farmacologia , Portadores de Fármacos/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Anfotericina B/efeitos adversos , Anfotericina B/uso terapêutico , Animais , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Ácido Desoxicólico/efeitos adversos , Ácido Desoxicólico/uso terapêutico , Portadores de Fármacos/farmacocinética , Combinação de Medicamentos , Liberação Controlada de Fármacos , Ácido Láctico/farmacocinética , Teste de Materiais , Camundongos , Paracoccidioides/efeitos dos fármacos , Paracoccidioides/fisiologia , Paracoccidioidomicose/tratamento farmacológico , Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Segurança , Succímero/química , Distribuição TecidualRESUMO
For some time Photodynamic Therapy and electrochemotherapy have been used as alternative therapies against skin cancer. The primary aim of this work was to develop, characterize, and evaluate the in vitro cytotoxic activity of new drug delivery systems based on chitosan nanoparticles containing aminolevulinic acid derivatives such as prodrug (5-ALA and its ester derivative 8-ALA). The second goal of this study was to evaluate the synergistic effect of a combination of classical Photodynamic Therapy and electrochemotherapy, which is routinely utilized to modulate and enhance the permeation of photosensitizers, prodrugs, and other active compounds through the skin, improving the efficiency of PDT in the treatment of cutaneous neoplasms.
Assuntos
Ácido Aminolevulínico/análogos & derivados , Ácido Aminolevulínico/administração & dosagem , Quitosana/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Eletroquimioterapia/métodos , Melanoma/tratamento farmacológico , Nanopartículas/administração & dosagem , Fotoquimioterapia/métodos , HumanosRESUMO
This research evaluated the effect of multiple-wave lasertherapy on the healing process of surgical wounds based on in vitro models denominated stem-dermal equivalents. These human skin models were obtained from a co-culture of dermal cells and bone marrow mesenchymal stem cells. The experimental tests were carried out using a LED portable to multiple waves (operating at 660 nm and 810 nm) at different doses to induce photobiostimulation (10 to 70 mJ.cm-2). Moreover, a photosensitizer drug was employed as a new advanced designed nanomaterial, being a nanoemulsion with biopolymers to obtain an efficient drug delivery system to release lipophilic compounds. The studies were performed considering the light combination application monitoring the kinetic contraction of the dermal equivalent model and the quantification of important macromolecules (as metaloproteases derivatives), related directly with wound healing process. Results showed that an appropriate photomodulation using the combination of both wavelengths (in the red and infrared range) is possible, such that it can contribute to wound healing therapy and/or other pathological skin disease treatment.
Assuntos
Indóis/administração & dosagem , Luz , Compostos Organometálicos/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação , Células Cultivadas , Técnicas de Cocultura , Emulsões , Fibroblastos , Gengiva/citologia , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Mesenquimais , Nanoestruturas , FotoquimioterapiaRESUMO
Loaded microspheres with a silicon (IV) phthalocyanine derivative (NzPC) acting as a photosensitizer were prepared from polyhydroxybutyrate-co-valerate (PHBHV) and poly(ecaprolactone) (PCL) polymers using the emulsification solvent evaporation method (EE). The aim of our study was to prepare two systems of these biodegradable PHBHV/PCL microspheres. The first one containing only photosensitizer previously incorporated in the PHBHV and poly(ecaprolactone) (PCL) microspheres and the second one with the post magnetization of the DDS with magnetic nanoparticles. Magnetic fluid is successfully used for controlled incorporation of nanosized magnetic particles within the micron-sized template. This is the first time that we could get a successful pos incorporation of nanosized magnetic particles in a previously-prepared polymeric template. This procedure opens a great number of possibilities of post-functionalization of polymeric micro or nanoparticles with different bioactive materials. The NzPC release profile of the systems is ideal for PDT, the zeta potential and the size particle are stable upon aging in time. In vitro studies were evaluated using gingival fibroblastic cell line. The dark citotoxicity, the phototoxicity and the AC magnetic field assays of the as-prepared nanomagnetic composite were evaluated and the cellular viability analyzed by the classical test of MTT.
Assuntos
Fibroblastos/fisiologia , Hipertermia Induzida/métodos , Indóis/administração & dosagem , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Fotoquimioterapia/métodos , Materiais Biocompatíveis , Linhagem Celular , Fibroblastos/citologia , Humanos , Isoindóis , Campos Magnéticos , Microesferas , Fármacos FotossensibilizantesRESUMO
The biofilms formed by opportunistic yeasts serve as a persistent reservoir of infection and impair the treatment of fungal diseases. The aim of this study was to evaluate photodynamic inactivation (PDI) of biofilms formed by Candida spp. and the emerging pathogens Trichosporon mucoides and Kodamaea ohmeri by a cationic nanoemulsion of zinc 2,9,16,23-tetrakis(phenylthio)-29H,31H-phthalocyanine (ZnPc). Biofilms formed by yeasts after 48 h in the bottom of 96-well microtiter plates were treated with the photosensitizer (ZnPc) and a GaAlAs laser (26.3 J cm(-2)). The biofilm cells were scraped off the well wall, homogenized, and seeded onto Sabouraud dextrose agar plates that were then incubated at 37°C for 48 h. Efficient PDI of biofilms was verified by counting colony-forming units (CFU/ml), and the data were submitted to analysis of variance and the Tukey test (p < 0.05). All biofilms studied were susceptible to PDI with statistically significant differences. The strains of Candida genus were more resistant to PDI than emerging pathogens T. mucoides and K. ohmeri. A mean reduction of 0.45 log was achieved for Candida spp. biofilms, and a reduction of 0.85 and 0.84, were achieved for biofilms formed by T. mucoides and K. ohmeri, respectively. Therefore, PDI by treatment with nanostructured formulations cationic zinc 2,9,16,23- tetrakis (phenylthio)- 29H, 31H- phthalocyanine (ZnPc) and a laser reduced the number of cells in the biofilms formed by strains of C. albicans and non-Candida albicans as well the emerging pathogens T. mucoides and K. ohmeri.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Indóis/farmacologia , Lasers , Compostos Organometálicos/farmacologia , Saccharomycetales/efeitos dos fármacos , Trichosporon/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Candida/fisiologia , Contagem de Colônia Microbiana , Emulsões/farmacologia , Humanos , Mucosa Bucal/microbiologia , Nanoestruturas , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Saccharomycetales/fisiologia , Trichosporon/fisiologiaRESUMO
Nanotechnology and tissue engineering are promising scientific fields in the development of advanced materials useful to human health. This article describes the preparation of a nanocarrier for the controlled release of a photosensitizer compound associated with low-level light therapy for skin wound healing treatment and applicable to other skin diseases. A biological model was used as an in vitro skin equivalent based on a three-dimensional culture of fibroblasts and mesenchymal stem cells and denominated by dermal equivalent (DE). Results show that it is possible to use the photomodulation process to control the wound healing in a scratching process and to induce the biomolecules release, both of which are related with the inflammatory wound healing process. In the studies, the MMP-2 and MMP-9 expression from zymography analyses were evaluated. All results showed a dependence on enzymatic activity relating to lowlevel laser applications which indicates a potential application in wound healing processes based on phototherapy and nanotechnology.
Assuntos
Indóis/farmacologia , Terapia com Luz de Baixa Intensidade/métodos , Células-Tronco Mesenquimais/efeitos da radiação , Compostos Organometálicos/farmacologia , Fotoquimioterapia/métodos , Pele/efeitos da radiação , Células da Medula Óssea , Técnicas de Cocultura , Emulsões , Fibroblastos/citologia , Humanos , Indóis/uso terapêutico , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanotecnologia , Compostos Organometálicos/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiaçãoRESUMO
PURPOSE: To describe the presence of iris neovascularization in a rabbit-model of retinal neovascularization induced by the intravitreal injection of latex-derived angiogenic fraction microspheres (LAF). MATERIALS AND METHODS: Eight New Zealand rabbits received one intravitreal injection of PLGA (L-lactide-co-glycolide) microspheres with 50 ug of LAF in the right eye (Group A). Microspheres without the LAF (0.1 ml) were injected in controls (Group B; n = 8). Follow-up with clinical evaluation and iris fluorescein angiography was performed after 4 weeks when eyes were processed for light microscopy. RESULTS: All eyes from Group A showed significant vascular dilation, conjunctival hyperemia and neovascularization on the iris surface, after LAF injection. No vascular changes were observed in Group B. CONCLUSIONS: The intravitreal injection of microspheres containing the LAF can induce rubeosis iridis in rabbits and could be used as a simple experimental model for iris neovascularization.
Assuntos
Indutores da Angiogênese/toxicidade , Glaucoma Neovascular/etiologia , Iris/irrigação sanguínea , Látex/toxicidade , Neovascularização Patológica/induzido quimicamente , Indutores da Angiogênese/administração & dosagem , Animais , Modelos Animais de Doenças , Progressão da Doença , Portadores de Fármacos , Feminino , Angiofluoresceinografia , Fundo de Olho , Glaucoma Neovascular/patologia , Injeções Intravítreas , Iris/efeitos dos fármacos , Ácido Láctico , Látex/administração & dosagem , Microesferas , Neovascularização Patológica/complicações , Neovascularização Patológica/patologia , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Fatores de RiscoRESUMO
UV-VIS-Spectrophotometric and spectrofluorimetric methods have been developed and validated allowing the quantification of chloroaluminum phthalocyanine (CIAIPc) in nanocarriers. In order to validate the methods, the linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, and selectivity were examined according to USP 30 and ICH guidelines. Linearities range were found between 0.50-3.00 microg x mL(-1) (Y = 0.3829 X [CIAIPc, microg x mL(-1)] + 0.0126; r = 0.9992) for spectrophotometry, and 0.05-1.00 microg x mL(-1) (Y = 2.24 x 10(6) X [CIAIPc, microg x mL(-1)] + 9.74 x 10(4); r = 0.9978) for spectrofluorimetry. In addition, ANOVA and Lack-of-fit tests demonstrated that the regression equations were statistically significant (p<0.05), and the resulting linear model is fully adequate for both analytical methods. The LOD values were 0.09 and 0.01 microg x mL(-1), while the LOQ were 0.27 and 0.04 microg x mL(-1) for spectrophotometric and spectrofluorimetric methods, respectively. Repeatability and intermediate precision for proposed methods showed relative standard deviation (RSD) between 0.58% to 4.80%. The percent recovery ranged from 98.9% to 102.7% for spectrophotometric analyses and from 94.2% to 101.2% for spectrofluorimetry. No interferences from common excipients were detected and both methods were considered specific. Therefore, the methods are accurate, precise, specific, and reproducible and hence can be applied for quantification of CIAIPc in nanoemulsions (NE) and nanocapsules (NC).