RESUMO
The aim of this study was to further evaluate the antitumoral effect of (PhSe)2-loaded polymeric nanocapsules (NC (PhSe)2) against a resistant melanoma cell line (SK-Mel-103) and develop a xanthan gum-based hydrogel intending the NC (PhSe)2 cutaneous application. For the in vitro evaluation, cells were incubated with free (PhSe)2 or NC (PhSe)2 (0.7-200 µM) and after 48 h the MTT assay, propidium iodide uptake (necrosis marker) and nitrite levels were assessed. The hydrogels were developed by thickening of the NC (PhSe)2 suspension or (PhSe)2 solution with xanthan gum and characterized in terms of average diameter, polydispersity index, pH, drug content, spreadability, rheological profiles and in vitro permeation in human skin. The results showed that NC (PhSe)2 provided a superior antitumoral effect in comparison to free (PhSe)2 (IC50 value of 47.43 µM and 65.05 µM, respectively) and increased the nitrite content. Both compound forms induced propidium iodide uptake, suggesting a necrosis-related pathway could be involved in the cytotoxic action of (PhSe)2. All hydrogels showed pH values around 7, drug content close to the theoretical values (5 mg/g) and mean diameter in the nanometric range. Besides, formulations were classified as non-Newtonian flow with pseudoplastic behavior and suitable spreadability factor. Skin permeation studies revealed that the compound content was higher for the nano-based hydrogel in the dermis layer, demonstrating its superior permeation, achieved by the compound encapsulation. It is the first report on an adequate formulation development for cutaneous application of NC (PhSe)2 that could be used as an adjuvant treatment in melanoma therapy.
Assuntos
Antineoplásicos/farmacologia , Derivados de Benzeno/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Melanoma Experimental/tratamento farmacológico , Nanocápsulas/química , Compostos Organosselênicos/farmacologia , Polissacarídeos Bacterianos/química , Animais , Antineoplásicos/química , Derivados de Benzeno/química , Linhagem Celular , Humanos , Camundongos , Compostos Organosselênicos/química , Permeabilidade/efeitos dos fármacos , Polímeros/químicaRESUMO
The current study developed an innovative Pemulen® TR2 hydrogel containing silibinin-loaded pomegranate oil-based nanocapsules (HP-NC SB) intending cutaneous application. The formulation anti-inflammatory activity in an in vivo model and biometric studies on the skin of healthy volunteers were also performed. The nanocapsules were prepared using the interfacial deposition of preformed polymer technique and the hydrogels were obtained by thickening of nanocapsules suspension with Pemulen® TR2. Formulations with free compound, vehicle and blank nanocapsules were also produced. The hydrogels were evaluated concerning pH, silibinin content, particle size, spreadability profile, rheology, in vitro drug release, cutaneous permeation, bioadhesive potential and cutaneous biometry evaluation. Furthermore, a model of contact dermatitis croton oil-induced in mice was performed to evaluate the hydrogels anti-inflammatory potential. The formulations presented adequate characteristics for skin administration: particle within nanometric size, pH values in the acid range, silibinin content close theoretical values (1â¯mg/g) and non-Newtonian pseudoplastic behavior. Nano-based hydrogels showed high bioadhesive properties, increased silibinin in vitro release profile and its retention in the stratum corneum. The best anti-inflammatory effect was exhibited by HP-NC SB, which reduced both ear edema and inflammatory cells infiltration in comparison to the induced group. Furthermore, cutaneous biometric evaluation showed that formulations containing free or nanoencapsulated silibinin caused no modification in normal skin conditions (pH, tissue hydration, transepidermal water loss and erythema). In summary, the results demonstrated that the Pemulen® TR2 hydrogel containing NC SB was successfully developed, indicating its potential as an alternative treatment for irritant contact dermatitis.
Assuntos
Anti-Inflamatórios/administração & dosagem , Dermatite de Contato/tratamento farmacológico , Edema/tratamento farmacológico , Hidrogéis/administração & dosagem , Nanocápsulas/administração & dosagem , Silibina/administração & dosagem , Administração Cutânea , Animais , Anti-Inflamatórios/química , Óleo de Cróton , Liberação Controlada de Fármacos , Feminino , Humanos , Hidrogéis/química , Irritantes , Masculino , Camundongos , Nanocápsulas/química , Silibina/química , Absorção CutâneaRESUMO
The present study shows the development of a topical formulation (hydrogel) containing silibinin-loaded pomegranate oil based nanocapsules suspension and its evaluation as an alternative for the treatment of cutaneous UVB radiation-induced damages. For this, an animal model of skin injury induced by UVB radiation was employed. Gellan gum was used as gel forming agent by its direct addition to nanocapsules suspension. The hydrogels showed adequate pH values (5.6-5.9) and a silibinin content close to the theoretical value (1mg/g). Through vertical Franz diffusion cells it was demonstrated that nanocapsules decreased the silibinin retention in the semisolid formulation. All formulations were effective in reducing mice ear edema and leukocyte infiltration induced by UVB radiation 24h after the treatments. After 48h, only the hydrogels containing nanocapsules or silibinin associated with pomegranate oil demonstrated anti-edematogenic effect, as well as the positive control (hydrogel containing silver sulfadiazine 1%). After 72h, the hydrogel containing unloaded pomegranate oil based nanocapsules still presented a small activity. In conclusion, the results of this investigation demonstrated the feasibility to prepare a semisolid formulation presenting performance comparable to the traditional therapeutic option for skin burns (silver sulfadiazine) and with prolonged in vivo anti-inflammatory activity compared to the non-nanoencapsulated compounds.