RESUMO
Phloretin and 6-ketocholestanol are penetration enhancers for percutaneous delivery of certain topically applied drugs. In the present study some physicochemical experiments have been performed to elucidate the mechanism of action of phloretin and 6-ketocholestanol. The penetration enhancing effect of phloretin and 6-ketocholestanol is believed to be due to their increase of the fluidity of the intercellular lipid bilayers of the stratum corneum. Phospholipid vesicles were chosen as a simple model to represent these bilayers. The effect of phloretin and 6-ketocholestanol on phase transition temperature and enthalpy was studied using differential scanning calorimetry. Beside of that the size of liposomes was monitored when the amount of penetration enhancer in the liposome preparation was changed. Addition of increasing amounts of phloretin and 6-ketocholestanol to the bilayer resulted in lowering of phase transition temperatures and increasing the enthalpy. Additionally the size of the liposomes was increased when penetration enhancer was added. The results suggest that phloretin as well as 6-ketocholestanol would interact with stratum corneum lipids in a similar manner, both reduce the diffusional resistance of the stratum corneum to drugs with balanced hydrophilic-lipophilic characteristics.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Cetocolesteróis/química , Membranas Artificiais , Modelos Químicos , Floretina/química , Fosfolipídeos/química , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Interações Medicamentosas , Cetocolesteróis/metabolismo , Lipossomos , Floretina/metabolismo , Fosfolipídeos/metabolismoRESUMO
The viscoelastic properties of two transparent semisolid preparations, one consisting of surfactant, paraffin oil, and water (BAS), and the other consisting of surfactant, cetylstearyl-2-ethylhexanoate, and water (CUBO), were characterized by oscillatory measurements. In (1)H-NMR diffusion experiments it was confirmed that the formulations are O/W systems, and the three-dimensional packing of the closed globular aggregates form a cubic structure. Moreover, standard diffusion experiments with porcine skin using Franz cells were performed with incorporated diclofenac-sodium and cyproterone acetate, respectively. The cumulative amount released after 48 h of diclofenac-sodium were excellent with 665.28 microg/cm(2) and with 36.7 microg/cm(2) for cyproterone acetate. The new drug-containing formulations were also prepared as transdermal patches by using carrageenan as a matrix. In diffusion studies zero-order kinetics was found for both drugs, but with a higher lag time for cyproterone acetate. The total work of adhesion was analyzed by tensile studies on porcine skin and found to be very good. The presented cubic gels as well as mixtures with carrageenan are promising alternative drug carrier systems for topical pharmaceutical as well as cosmetics.
Assuntos
Acetato de Ciproterona/farmacocinética , Diclofenaco/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Animais , Carragenina/farmacologia , Cátions/química , Química Farmacêutica , Acetato de Ciproterona/química , Acetato de Ciproterona/farmacologia , Diclofenaco/química , Diclofenaco/farmacologia , Difusão , Excipientes/farmacologia , Liofilização/métodos , Géis , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Prótons , Reologia , Suínos , ViscosidadeRESUMO
The use of polymers for skin preparations is manifold. Requirements of such polymers are dependent on the formulation types. The most applied polymers on skin belong to various classes, for example to cellulose derivatives, chitosan, carageenan, polyacrylates, polyvinylalcohol, polyvinylpyrrolidone and silicones. They are gelating agents, matrices in patches and wound dressings, anti-nucleants and penetration enhancers. Correlations between commercially available products and results of new scientific investigations are often difficult or not possible, because of the lack of comparative data especially for transdermal patches. Finally, two promising future trends of polymeric systems, gene delivery and tissue engineering, are discussed.
Assuntos
Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas/administração & dosagem , Polímeros/química , Adjuvantes Farmacêuticos/química , Administração Cutânea , Animais , Bandagens , Emulsões/química , Géis/química , Humanos , Pomadas/química , Absorção Cutânea , Dermatopatias/tratamento farmacológicoRESUMO
In the present study, we investigated the feasibility of enhancing the transport of the model drug sodium-fluorescein across rat, porcine and human skin by treating it with phloretin and 6-ketocholestanol. Both 6-ketocholestanol and phloretin were incorporated into unilamellar liposomes and used as a skin pre-treatment. Afterwards standard diffusion experiments with Franz-type diffusion cells were performed. The results indicate a positive effect of 6-ketocholestanol on the sodium-fluorescein diffusion in all skin types, whereas phloretin had no significant influence compared to the control in human skin. In contrast to this, phloretin had a significant positive effect in rat as well as in porcine skin after 30 h of diffusion. In addition to the permeation studies, the human skin samples were analysed by confocal laser scanning microscopy for direct visualisation of the sodium-fluorescein. As expected the results of the diffusion experiments were confirmed by this microscopic method.
