RESUMO
The aim of this study is to report the case of a 4-month-old Beagle dog diagnosed with Musladin-Lueke syndrome. The dog appeared to walk on the digits ("tiptoes") with all limbs during ambulation and rigid extension of the carpus, elbow, tarsus, and knee joints during ambulation. Thickening of the fur and auricular cartilage, reduction in radiocarpal, and tibiotarsal joint amplitude, macrocephaly, and lateralized eyes were noticed on physical examination. Echocardiography showed reduced mobility and altered (tortuous) valve morphology. Bilateral abdominal cryptorchidism was confirmed by ultrasonography. Musladin-Lueke syndrome was the presumptive diagnosis, based on the clinical signs presented. The diagnosis was confirmed after DNA testing performed by serial collection of saliva. This is the first paper that describes unprecedented cardiac and reproductive changes of Musladin-Lueke syndrome in which the dog was followed for 2 years, presenting a good quality of life.
Assuntos
Doenças do Cão , Animais , Cães , Masculino , Doenças do Cão/diagnóstico , Doenças do Cão/genética , Doenças do Cão/patologia , Qualidade de Vida , Caminhada , SíndromeRESUMO
The aim of this study was to propose the use of spray-dried mucoadhesive carvedilol-loaded nanocapsules in the formulation of sublingual tablets. There is no previous report describing the preparation of tablets containing spray-dried nanocapsules or tablets containing nanocapsules, neither prepared by direct compression nor for sublingual administration. Tablets of 6 mm of diameter and 2.7 ± 0.2 mm of height were obtained with a mean weight of 44 ± 4 mg, carvedilol content of 0.164 ± 0.017 mg, and a disintegration time less than 25 min. They were produced using a force of 4.7 ± 1.6 kgf. The release profile of carvedilol from the tablets was evaluated using the dialysis bag method. In parallel, the release of nanocapsules from the tablet structure into the release medium was evaluated using dynamic light scattering. Nanocapsules that were released from the tablets into the release medium exhibited similar particle size distributions after recovery as in their original liquid suspension, without losing their original ability to control drug release. Therefore, sublingual tablets may be produced from spray-dried drug-loaded nanocapsules using a direct compression technique, providing a useful pharmaceutical approach for drugs that undergo first pass metabolism, such as carvedilol.
Assuntos
Carvedilol/química , Nanocápsulas/química , Comprimidos/química , Administração Sublingual , Química Farmacêutica/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Nanomedicina/métodos , Tamanho da Partícula , Polímeros/química , Suspensões/químicaRESUMO
Cervical cancer is associated with the human papilloma virus (HPV) and nowadays is the fourth most frequent cancer among women. One of the treatments for this disease is based on the application of imiquimod. In this study, we postulated that the use of imiquimod in nanoemulsion results in a better antitumoral effect than the drug administered in its nonencapsulated form for the treatment of cervical cancer. Permeability studies using vaginal mucosa, as membrane, and in vitro studies involving cervical cancer cells (viability, clonogenic assay, and cell death analysis) were performed. We showed that low amount of encapsulated imiquimod permeated the vaginal mucosa. However, a higher percentage of cells died after the treatment with low amount (3.0 µmol L-1) of the formulation compared to the free drug. In addition, the innovative formulation presented a combinatory mechanism of cell death involving autophagy and apoptosis. Our results demonstrate that the imiquimod-loaded nanoemulsioncan be an alternative product for the treatment of cervical cancer validating the hypothesis.
Assuntos
Imiquimode/administração & dosagem , Papillomaviridae/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Composição de Medicamentos , Emulsões , Feminino , Humanos , Nanopartículas , Suínos , Neoplasias do Colo do Útero/virologiaRESUMO
Doxazosin has been evaluated for the treatment of several types of cancer. Here, the antitumor effect of the nanoencapsulated form of doxazosin was evaluated in an in vitro model of breast cancer (MCF7 cell line). Doxazosin-loaded polymeric nanocapsules (DXZ-NC) were produced by interfacial deposition of preformed polymer with homogeneous aspect, spherical shape, mean diameter of about 130nm, positive zeta potential (+5mV), and encapsulation efficiency close to 35%. The Alamar Blue® assay and cell counting were carried out to assess cell viability and cell number, respectively. Mechanism of death was evaluated by Annexin/Propidium Iodide staining, while the long-term response was assessed using the clonogenic assay. Nuclear morphometric analysis was investigated using the NMA technique. A significant decrease in cell viability and clonogenicity was observed after the treatment with DXZ-NC when compared to the non-encapsulated drug. All treatments induced apoptosis as the main mechanism of toxicity. In conclusion, the nanoencapsulation of doxazosin improved its in vitro effects in MCF7 cells, without changing the mechanism of cell death underlying its toxicity. This approach was fundamental to reduce the long-term in vitro ability of the remaining tumor cells to form new colonies after the treatment, potentially reducing the risk of tumor recurrence.
Assuntos
Neoplasias da Mama/patologia , Doxazossina/farmacologia , Nanocápsulas/química , Contagem de Células , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , Liberação Controlada de Fármacos , Feminino , Humanos , Células MCF-7 , Nanocápsulas/ultraestrutura , Tamanho da PartículaRESUMO
A videocirurgia é atualmente uma das principais ferramentas operatórias, com vantagens que incluem menor estresse, incisões e dor pós-operatória quando comparada aos procedimentos abertos. Objetivou-se comparar o processo inflamatório e o estresse oxidativo resultantes das técnicas de ovário-histerectomia (OVH) convencional e videoassistida, com dois portais em cadelas, por meio de hemograma, avaliação de acetilcolinesterase, butirilcolinesterase, catalase e malondialdeído séricos, imediatamente antes da operação e duas, seis, 12, 24, 48 e 72 horas após a cirurgia. Observou-se menor estresse cirúrgico nas pacientes operadas pela técnica videoassistida, e sugere-se que a técnica convencional possa implicar peroxidação lipídica, mesmo com o uso de anti-inflamatório.(AU)
Videosurgery is currently a very important surgical tool with several benefits over the open surgery, including less surgical stress, shorter incisions and less postoperative pain. The purpose of this study was to compare the inflammatory process and oxidative stress between conventional and two-port laparoscopic-assisted ovariohisterectomy (OVH) in bitches. Complete blood counting, serum acetylcholinesterase, butyrylcholinesterase, catalase and malondialdehyde were assessed on the baseline and at two, six, 12, 24, 48 and 72 hours after surgery. The patients submitted to the videoassisted technique presented lower inflammatory response. There are suggestions that the conventional technique promotes lipid peroxidation, even with the use of anti-inflammatories.(AU)
Assuntos
Animais , Cães , Biomarcadores/análise , Ovariectomia/veterinária , Estresse Oxidativo , Cirurgia Vídeoassistida/veterinária , Acetilcolinesterase , Butirilcolinesterase/análise , Peroxidação de LipídeosRESUMO
A videocirurgia é atualmente uma das principais ferramentas operatórias, com vantagens que incluem menor estresse, incisões e dor pós-operatória quando comparada aos procedimentos abertos. Objetivou-se comparar o processo inflamatório e o estresse oxidativo resultantes das técnicas de ovário-histerectomia (OVH) convencional e videoassistida, com dois portais em cadelas, por meio de hemograma, avaliação de acetilcolinesterase, butirilcolinesterase, catalase e malondialdeído séricos, imediatamente antes da operação e duas, seis, 12, 24, 48 e 72 horas após a cirurgia. Observou-se menor estresse cirúrgico nas pacientes operadas pela técnica videoassistida, e sugere-se que a técnica convencional possa implicar peroxidação lipídica, mesmo com o uso de anti-inflamatório.(AU)
Videosurgery is currently a very important surgical tool with several benefits over the open surgery, including less surgical stress, shorter incisions and less postoperative pain. The purpose of this study was to compare the inflammatory process and oxidative stress between conventional and two-port laparoscopic-assisted ovariohisterectomy (OVH) in bitches. Complete blood counting, serum acetylcholinesterase, butyrylcholinesterase, catalase and malondialdehyde were assessed on the baseline and at two, six, 12, 24, 48 and 72 hours after surgery. The patients submitted to the videoassisted technique presented lower inflammatory response. There are suggestions that the conventional technique promotes lipid peroxidation, even with the use of anti-inflammatories.(AU)
Assuntos
Animais , Cães , Biomarcadores/análise , Estresse Oxidativo , Ovariectomia/veterinária , Cirurgia Vídeoassistida/veterinária , Peroxidação de Lipídeos , Acetilcolinesterase , Butirilcolinesterase/análiseRESUMO
This study aimed to evaluate in vitro and in vivo trypanocidal activity of free and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was evaluated to verify their lethal effect on T. evansi. To perform the in vivo tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg(-1), intraperitoneally [i.p.]) and C-LNCs (10 mg kg(-1), i.p.) during 6 days, with the results showing that these treatments significantly attenuated the parasitaemia. Infected untreated rats showed protein peroxidation and an increase of nitrites/nitrates, whereas animals treated with curcumin showed a reduction on these variables. As a result, the activity of antioxidant enzymes (superoxide dismutase and catalase) differs between groups (P<0.05). Infected animals and treated with CURC exhibited a reduction in the levels of alanine aminotransferase and creatinine, when compared with the positive control group. The use of curcumin in vitro resulted in a better parasitaemia control, an antioxidant activity and a protective effect on liver and kidney functions of T. evansi-infected adult male Wistar rats.
Assuntos
Curcumina/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos , Tripanossomíase/tratamento farmacológico , Produtos da Oxidação Avançada de Proteínas/sangue , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Catalase/sangue , Creatinina/metabolismo , Curcumina/administração & dosagem , Cães , Concentração de Íons de Hidrogênio , Rim/parasitologia , Rim/patologia , Rim/fisiopatologia , Fígado/enzimologia , Fígado/parasitologia , Fígado/patologia , Masculino , Nanocápsulas , Nitratos/sangue , Nitritos/sangue , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Ratos , Ratos Wistar , Superóxido Dismutase/sangue , Tripanossomicidas/administração & dosagem , Tripanossomíase/patologiaRESUMO
Topical glucocorticoids (TG) such as dexamethasone (DEX) have been used for decades for the treatment of skin diseases. However, TG present well-documented side effects and their delivery to the skin is often insufficient. Therefore, many efforts have been undergone to improve the amount of drug delivered to the skin and to reduce side effects at the same time. In this work, the feasibility of DEX-submicron polymeric particles (SP) prepared by vibrational spray-drying as an approach to overcome the challenges associated with the topical administration of this drug class was evaluated. DEX was homogeneously dispersed in the SP matrix, according to confocal Raman microscopy analysis. Drug-loaded SP were incorporated into the oil phase of oil-in-water emulsions (creams). The formulation containing polymeric submicron particles (C-SP) showed controlled drug release kinetics and a significant drug accumulation in skin compared to formulations containing non-polymeric particles or free drug. DEX accumulation in the stratum corneum was evaluated by tape stripping and a depot effect over time was observed for C-SP, while the formulation containing the free drug showed a decrease over time. Similarly, C-SP presented higher drug retention in epidermis and dermis in skin penetration studies performed on pig skin in Franz diffusion cells, while drug permeation into the receptor compartment was negligible. It was demonstrated, for the first time, the advantageous application of submicron polymeric particles obtained by vibrational spray-drying in semisolid formulations for cutaneous administration to overcome challenges related to the therapy with TG such as DEX.
Assuntos
Dexametasona/administração & dosagem , Portadores de Fármacos/química , Glucocorticoides/administração & dosagem , Polímeros/química , Absorção Cutânea , Pele/metabolismo , Animais , Dexametasona/farmacocinética , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Emulsões , Glucocorticoides/farmacocinética , Técnicas In Vitro , Microscopia Confocal , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Pele/efeitos dos fármacos , Propriedades de Superfície , Sus scrofa , Distribuição Tecidual , VibraçãoRESUMO
The oxidizing capacity and skin penetration of a commercial nanosized ZnO, Nanosun™ (Micronisers-Australia), were evaluated in vitro using porcine skin. Nanosun™ was initially characterized regarding its photo-reactivity and size distribution. An assay using methylene blue was performed to confirm the Nanosun™ photo-reactivity by exposing the labile molecule to UVA irradiation in the presence and absence of the nanosized ZnO. The nanosized ZnO was photo-reactive, reducing the methylene blue concentration to 7% while its concentration remained constant in the control formulation (without ZnO). The product label states that the average particle size is 30 nm. X-ray diffraction, nitrogen sorption and UV-spectrophotometry confirmed the presence of nanometric particles of approximately 30 nm. On the other hand, laser diffractometry showed micrometric particles in the size distribution profile. These analyses indicated that the nanoparticles are arranged as agglomerates and aggregates of micrometric proportions ranging from 0.6 to 60 µm. The skin lipid peroxidation was determined by the formation of thiobarbituric acid reactive species (TBARS) and quantified by UV-spectrophotometry. When exposed to UVA radiation the nanosized ZnO applied porcine skin showed a lower production of TBARS (7.2 ± 1.5 nmol g(-1)) than the controls, the MCT applied porcine skin (18.4 ± 2.8 nmol g(-1)) and the blank porcine skin (14.0 ± 2.0 nmol g(-1)). The penetration of ZnO nanoparticles was studied by scanning electron microscopy and energy dispersive X-ray spectroscopy. The tested ZnO particles did not penetrate into viable layers of the intact porcine skin. The particles tend to accumulate on the skin folds and in these regions they may penetrate into the horny layer.
Assuntos
Óxido de Zinco/química , Animais , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Azul de Metileno/química , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Espectrometria por Raios X , Suínos , Raios UltravioletaRESUMO
Resveratrol and curcumin are natural antioxidants found in the human diet that have been used in the prevention and treatment of different diseases associated with oxidative stress. Aiming to improve the antioxidant effects of resveratrol and curcumin, lipid-core nanocapsules containing the combination of both polyphenols were developed. Physicochemical characteristics were evaluated and compared to the formulations containing each polyphenol individually. Co-encapsulation did not influence nanotechnological characteristics, and all formulations presented mean diameter around 200 nm, low polydispersity index, and encapsulation efficiency close to 100%. Nanoencapsulation increases the photostability of resveratrol and curcumin, and co-encapsulation improves resveratrol photostability. The in vitro antioxidant activity of polyphenols against HO radicals was enhanced by nanoencapsulation, and a better effect was observed after their co-nanoencapsulation. Also, nanocapsules exhibited controlled release profile, for both polyphenols. The results showed that the strategy to co-encapsulate resveratrol and curcumin is a promising approach to improve the performance of medicines used to prevent and treat diseases associated with oxidative stress.
Assuntos
Curcumina/administração & dosagem , Lipídeos/química , Nanocápsulas/química , Estilbenos/administração & dosagem , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Sistemas de Liberação de Medicamentos , Radicais Livres , Humanos , Concentração de Íons de Hidrogênio , Inflamação , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Nanotecnologia , Estresse Oxidativo , Tamanho da Partícula , Polifenóis/química , ResveratrolRESUMO
The aim of this study was to evaluate, for the first time, the antifungal efficacy of nanocapsules and nanoemulsions containing Melaleuca alternifolia essential oil (tea tree oil) in an onychomycosis model. The antifungal activity of nanostructured formulations was evaluated against Trichophyton rubrum in two different in vitro models of dermatophyte nail infection. First, nail powder was infected with T. rubrum in a 96-well plate and then treated with the formulations. After 7 and 14 days, cell viability was verified. The plate counts for the samples were 2.37, 1.45 and 1.0 log CFU mL(-1) (emulsion, nanoemulsion containing tea tree oil and nanocapsules containing tea tree oil, respectively). A second model employed nails fragments which were infected with the microorganism and treated with the formulations. The diameter of fungal colony was measured. The areas obtained were 2.88 ± 2.08 mm(2), 14.59 ± 2.01 mm(2), 40.98 ± 2.76 mm(2) and 38.72 ± 1.22 mm(2) for the nanocapsules containing tea tree oil, nanoemulsion containing tea tree oil, emulsion and untreated nail, respectively. Nail infection models demonstrated the ability of the formulations to reduce T. rubrum growth, with the inclusion of oil in nanocapsules being most efficient.
Assuntos
Portadores de Fármacos , Nanocápsulas , Óleo de Melaleuca/farmacologia , Trichophyton/efeitos dos fármacos , Contagem de Colônia Microbiana , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Viabilidade Microbiana/efeitos dos fármacos , Unhas/microbiologia , SuspensõesRESUMO
OBJECTIVE: The use of spray-dried powders containing tretinoin-loaded nanocapsules instead of the original liquid suspension, aimed at the preparation of dermatological nanomedicines with improved photostability, was investigated. METHODS: Powders were prepared using lactose as a drying adjuvant. Hydrogels were prepared using two approaches: dispersing Carbopol Ultrez 10 in an aqueous redispersion of the powder or incorporating the powder in previously formed hydrogels. RESULTS AND DISCUSSION: The photodegradation of tretinoin in hydrogels prepared with the powders showed similar half-life times (around 19.5 h) compared to preparations with the original liquid nanocapsules (20.7 ± 1.4 h), regardless of the preparation approach. In addition, the topical nanomedicines prepared with the spray-dried powders presented a significant improvement in tretinoin photostability compared to the formulation containing the non-encapsulated drug. CONCLUSION: This study verified that the addition of the spray-dried powders containing tretinoin-loaded lipid-core nanocapsules to hydrogels did not influence the photoprotection of the drug compared with the preparation procedure using the original liquid suspension.
Assuntos
Antineoplásicos/administração & dosagem , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Nanosferas/química , Pós , Tretinoína/administração & dosagem , Administração Tópica , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Dessecação , Portadores de Fármacos , Estabilidade de Medicamentos , Meia-Vida , Nanomedicina , Tamanho da Partícula , Fotólise , Polímeros , Suspensões , Tecnologia Farmacêutica/métodos , Tretinoína/química , Tretinoína/efeitos da radiação , Raios UltravioletaRESUMO
The influence of the spray-drying process on the ability of engineered lipid-core nanocapsules to protect tretinoin against UV degradation was evaluated. This approach represents a technological alternative to improve the microbiological stability, storage and transport properties of such formulations. Tretinoin-loaded lipid-core nanocapsules or tretinoin-loaded nanoemulsion were dispersed in lactose (10% w/v) and fed in the spray-drier to obtain a solid product (spray-dried powder containing tretinoin-loaded nanocapsules or nanoemulsion--SD-TTN-NCL or SD-TTN-NE, respectively). SD-TTN-NE showed a lower (p < or = 0.05) percentage of encapsulation (89 +/- 1%) compared to SD-TTN-NCL (94 +/- 2%). Redispersed SD-TTN-NCL and SD-TTN-NE showed z-average sizes of 204 +/- 2 nm and 251 +/- 9 nm, which were close to those of the original suspensions (220 +/- 3 nm and 239 +/- 14 nm, respectively). Similar percentage of photodegradation were determined for tretinoin loaded in nanocapsules (26.15 +/- 4.34%) or in the respective redispersed spray-dried powder (28.73 +/- 6.19 min) after 60 min of UVA radiation exposure (p > 0.05). Our experimental design showed for the first time that spray-dried lipid-core nanocapsules are able to protect tretinoin against UVA radiation, suggesting that the drying process did not alter the supramolecular structure of the lipid-core nanocapsules. Such powders are potential intermediate products for the development of nanomedicines containing tretinoin.
RESUMO
OBJECTIVE: Development of a hydrogel containing rutin at 0.025% (w/w) and evaluation of its in vivo efficacy in cutaneous wound healing in rats. METHODS: Hydrogels were prepared using Carbopol Ultrez® 10 NF and an aqueous dispersion of rutin in polysorbate 80. Hydrogels were characterized by means of pH measurement, rheological and spreadability analysis and rutin content determination by liquid chromatography. The in vivo healing effect was evaluated through the regression of skin lesions in rats and by analysis of oxidative stress. RESULTS AND DISCUSSION: Hydrogels showed adequate pH values (5.50-6.50) and pseudoplastic non-Newtonian behavior. After 5 days of treatment of wounds, hydrogels containing rutin presented a higher decrease in the wound area compared to the control hydrogels. Analysis of the oxidative stress showed a decrease in lipid peroxidation and protein carbonyl content as well as an increase in catalase activity after the treatment with the hydrogel containing rutin. Furthermore, this treatment increased total protein levels. CONCLUSION: This study shows for the first time the feasibility of using dermatological formulations containing rutin to improve skin wound healing.
Assuntos
Resinas Acrílicas/química , Polissorbatos/química , Rutina/administração & dosagem , Cicatrização/efeitos dos fármacos , Administração Cutânea , Animais , Química Farmacêutica/métodos , Cromatografia Líquida/métodos , Modelos Animais de Doenças , Estudos de Viabilidade , Hidrogéis , Concentração de Íons de Hidrogênio , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Reologia , Rutina/farmacologiaRESUMO
We developed a dermatological nanomedicine containing clobetasol propionate-loaded nanocapsules and evaluated its efficacy in a model of contact dermatitis after topical administration in rats. Hydrogels containing clobetasol propionate-loaded lipid-core nanocapsules or nanoemulsion (HG-CP-NC and HG-CP-NE, respectively) were prepared to evaluate the influence of the polymeric wall. They presented adequate pH values (5.50-6.50) and drug content (0.5 mg g(-1)) and their rheograms exhibited a non-Newtonian pseudoplastic behavior. The best in vitro drug release control was obtained for HG-CP-NC (1.03±0.11 µg cm(-2) h) compared to the HG-CP-NE (1.65±0.19 µg cm(-2) h) and the hydrogels containing nonencapsulated drug (HG-CP) (2.79±0.22 µg cm(-2) h). A significant increase in NTPDase activity was observed in lymphocytes for the group treated with 0.05% HG-CP-NC every other day compared to the group treated with 0.05% HG-CP every day using the in vivo model of contact dermatitis. The nanoencapsulation of clobetasol in nanocapsules led to a better control of the drug release from the semisolid nanomedicine and provided better in vivo dermatological efficacy.
Assuntos
Clobetasol/administração & dosagem , Clobetasol/química , Dermatite de Contato/tratamento farmacológico , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Administração Tópica , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Feminino , Hidrogéis/administração & dosagem , Hidrogéis/química , Concentração de Íons de Hidrogênio , Linfócitos/efeitos dos fármacos , Nanomedicina/métodos , Tamanho da Partícula , Ratos , Ratos WistarRESUMO
AIM: To evaluate the effect of cationic coating of polymeric nanocapsules in sunscreen formulations on the in vitro skin penetration of benzophenone-3. METHODS: Benzophenone-3-loaded nanocapsules were prepared by the interfacial deposition of poly(ε-caprolactone) and coated by using a chitosan solution. The nanoparticles were characterized and incorporated in hydrogels. The presence of nanoparticles in hydroxyethyl cellulose gels was observed by transmission electron microscopy and photon correlation spectroscopy. Penetration studies were carried out using Franz cells with porcine skin membranes. RESULTS: Benzophenone-3-loaded chitosan-coated nanocapsules presented a mean size of 202 ± 7 nm and positive zeta potential (+21 ± 1 mV), while these values for the uncoated nanocapsules were 175 ± 1 nm and -8 ± 1 mV. Penetration profiles showed that a higher amount of benzophenone-3 remained at the skin surface and a lower amount was found in the receptor compartment after the application of the formulation containing chitosan-coated nanocapsules compared to a formulation containing its free form. CONCLUSIONS: Hydrogel containing benzophenone-3 chitosan-coated nanocapsules represents an innovative formulation to overcome limitations of sunscreen daily use.
Assuntos
Benzofenonas/farmacocinética , Quitosana/química , Absorção Cutânea , Protetores Solares/farmacocinética , Administração Cutânea , Animais , Benzofenonas/administração & dosagem , Celulose/análogos & derivados , Celulose/química , Hidrogéis , Técnicas In Vitro , Microscopia Eletrônica de Transmissão , Nanocápsulas , Tamanho da Partícula , Poliésteres/química , Protetores Solares/administração & dosagem , SuínosRESUMO
Tretinoin-loaded conventional nanocapsules have showed a significant protection of this drug against UVC radiation. However, this formulation presents a limited stability on storage. We hypothesized that the association of tretinoin to lipid-core nanocapsules could increase the physicochemical stability of such formulations, focusing on the development of a reliable nanomedicine for parenteral administration. However, this advantage should still be accompanied by the known photoprotective effect of conventional polymeric nanocapsules against the exposure of tretinoin to UV radiation. Results showed that tretinoin-loaded lipid-core nanocapsules improved the physicochemical stability of formulations under storage, without changing their ability to protect tretinoin either against UVA or UVC radiation. In addition, the effect of nanoencapsulation on the antiproliferative and differentiation properties of tretinoin was studied on human myeloid leukemia cells (HL60 cells) showing that tretinoin-loaded lipid-core nanocapsules presents a longer antitumor efficiency compared to the free tretinoin. These results allow us to propose the current formulation (tretinoin-loaded lipid-core nanocapsules) as a promising parenteral nanomedicine for the treatment of acute promyelocytic leukaemia.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Lipídeos/química , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Tretinoína/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Células HL-60 , Humanos , Tretinoína/químicaRESUMO
The aim of the present work was to evaluate the feasibility to convert drug-loaded nanocapsule suspensions in a solid dosage form (tablets). Dexamethasone was used as a model drug due to its low aqueous solubility and fast drug release from conventional tablets. Granules containing dexamethasone-loaded nanocapsules were obtained by a wet granulation process using a dispersion of polyvinylpirrolidone/nanocapsules as a binder system. Granules were compressed in an eccentric compression machine (D-NC-T). A control formulation (tablets without nanocapsules) was also prepared (D-T). Tablets were characterized by means of mean weight, hardness, friability, diameter, thickness, disintegration time, drug content, morphological analysis by scanning electron microscopy (SEM), and in vitro drug release studies. D-NC-T showed adequate physicochemical characteristics according to the pharmacopeial requirements in terms of mean weight, hardness, friability, disintegration time and drug content. Intact nanocapsules in tablets were observed by SEM. In vitro drug release studies showed a slower release of dexamethasone from these tablets (D-NC-T) compared to the control formulation (D-T). Results showed that these tablets represent an interesting platform to the development of oral drug delivery systems containing polymeric nanocapsules.
Assuntos
Nanocápsulas/química , Comprimidos/química , Administração Oral , Química Farmacêutica/métodos , Dexametasona/administração & dosagem , Dexametasona/farmacocinética , Sistemas de Liberação de Medicamentos , Humanos , Técnicas In Vitro , Microscopia Eletrônica de Varredura , Nanocápsulas/ultraestrutura , Nanotecnologia , Polímeros/química , Povidona/químicaRESUMO
O objetivo desta pesquisa foi avaliar o efeito in vivo do óleo de citronela, no controle do carrapato bovino [Rhipicephalus (Boophilus) microplus], da mosca-dos-chifres (Haematobia irritans), da mosca-dos-estábulos (Stomoxys calcitrans) e da mosca doméstica (Musca domestica). Foram utilizadas 15 vacas da raça Holandês, distribuídas em três grupos de cinco animais cada um. Os tratamentos foram: controle negativo, amitraz a 0,025 por cento e óleo de citronela a 4 por cento. Para avaliação foram contadas fêmeas ingurgitadas de carrapato e moscas antes (média dos dias -3, -2, -1) e após a aplicação dos produtos nos dias 7, 14, 21 e 28; também foram coletadas amostras de sangue. Em 28 dias, houve necessidade de se reaplicar o amitraz e o fitoterápico para controlar a infestação com carrapato. A relação entre o número de aplicações foi de 1:2,5 para o amitraz e o óleo de citronela, respectivamente. A eficácia no controle do carrapato foi de 71,8 e 30,9 por cento para o amitraz e óleo de citronela a 4 por cento, respectivamente, na média pós-tratamento. Verificou-se baixo controle de moscas no tratamento constituído pelo fitoterápico. Não houve diferença entre os tratamentos para os parâmetros sanguíneos.
This study aimed to evaluate the in vivo effect of citronella oil on the control of bovine ticks [Rhipicephalus (Boophilus) microplus], horn flies (Haematobia irritans), stable flies (Stomoxys calcitrans) and houseflies (Musca domestica). Fifteen Holstein cows were allocated to three groups of five animals each. The treatments were: negative control, amitraz at 0.025 percent and citronella oil at 4 percent. Engorged female ticks and flies were counted before (mean of days -3, -2, -1) and at 7, 14, 21 and 28 days after treatment; blood samples were also collected. Within 28 days, amitraz and the phytotherapic agent had to be reapplied to control tick infestation. The relationship among the number of applications was 1:2.5 for amitraz and citronella oil, respectively. The efficacy of tick control was, on average, 71.8 and 30.9 percent for amitraz and citronella oil at 4 percent respectively, post-treatment. Lower control of flies was observed for the phytotherapic group. There was no difference among treatments for blood parameters.
Assuntos
Animais , Bovinos , Bovinos/parasitologia , Controle de Insetos/métodos , Cymbopogon/parasitologia , Ectoparasitoses/prevenção & controle , Óleos Voláteis/análise , Carrapatos/parasitologia , Inseticidas/análise , Inseticidas/uso terapêutico , Muscidae/parasitologiaRESUMO
CONTEXT: Our group previously reported the development of dexamethasone-loaded polymeric nanocapsules as an alternative for topical dermatological treatments. OBJECTIVE: Our study aimed to prepare and characterize a hydrogel containing this system to improve the effectiveness of the glucocorticoid for cutaneous disorders. METHODS: For the antiproliferative activity assay, a dexamethasone solution and D-NC were tested on Allium cepa root meristem model. D-NC were prepared by the interfacial deposition of preformed polymer. Hydrogels were prepared using Carbopol Ultrez 10 NF, as polymer, and characterized according to the following characteristics: pH, drug content, spreadability, viscosity, and in vitro drug release. RESULTS AND DISCUSSION: Nanocapsules showed mean particle size and zeta potential of 201 +/- 6 and -5.73 +/- 0.42 nm, respectively. They demonstrated a lower mitotic index (4.62%) compared to free dexamethasone (8.60%). Semisolid formulations presented acidic pH values and adequate drug content (between 5.4% and 6.1% and 100% and 105%, respectively). The presence of nanocapsules in hydrogels led to a decrease in their spreadability factor. Intact nanoparticles were demonstrated by TEM as well as by dynamic light scattering (mean particle size < 300 nm). In vitro studies showed a controlled dexamethasone release from hydrogels containing the drug associated to the nanocapsules following the Higuchi's squared root model (k = 20.21 +/- 2.96 mg/cm(2)/h(1/2)) compared to the hydrogels containing the free drug (k = 26.65 +/- 2.09 mg/cm(2)/h(1/2)). CONCLUSION: Taking all these results together, the hydrogel containing D-NC represent a promising approach to treat antiproliferative-related dermatological disorders.