The effects of betamethasone dipropionate and fish oil on HaCaT proliferation and apoptosis.

The current work examined the effect of fish oil (FO) and betamethasone dipropionate (BD) on the growth of immortalized HaCaT keratinocytes. HaCaT cells were grown and treated with FO and/or BD, and proliferation determined using the MTT method. The cells were further probed by immunocytochemistry (ICC) techniques for apoptosis using Cleaved Caspase-3 Asp175, and inflammatory processes using cyclooxygenase-2 (COX-2). The addition of FO increased the inhibition of HaCaT cells by 27.2%, from 43.15% to 70.35% compared to BD alone (p 0.034). FO alone appeared to induce expression of Asp175 and the effect was greater in combination with BD. The net effect, however, were less than BD alone. Similar observations were seen with regards to COX-2 inhibition. The added benefits of FO to the effect of BD on the inhibition of cell growth, induction of apoptosis and inhibition of inflammation have now been demonstrated on a cellular level. Each of these activities supports beneficial effects in hyperproliferative skin disorders, such as psoriasis.

Delivery of atovaquone and proguanil across sublingual membranes, in vitro.

Malarone(™), a combination of atovaquone (AT) and proguanil (PR), is indicated for the prophylaxis and treatment of uncomplicated Plasmodium falciparum malaria. This study aimed to determine in vitro the feasibility of delivering the combination of AT and PR as a spray formulation via the sublingual route, using Franz diffusion cells incorporating porcine sublingual mucosa. Firstly, 1 mg mL(-1) of each drug in 20% 1,8-Cineole in ethanol was used; and secondly, 5 mg mL(-1) AT and 1 mg mL(-1) PR in 20% 1-methyl-2-pyrrolidone in ethanol was examined, dosed every 2 h over a 12-h period and receptor phase samples were analyzed by HPLC. From the first study, mean fluxes for AT and PR were 12.89 ± 1.2 and 5.88 ± 0.9 µg cm(-2) h(-1) respectively; pharmacokinetic calculations indicated that these fluxes were insufficient to achieve the target plasma concentrations for AT and PR of 1.4 µg mL(-1) and 200 ng mL(-1) respectively, in the treatment of falciparum malaria. However, in the second study, the fluxes of AT and PR increased to 50.92 ± 20.8 and 12.01 ± 1.5 µg cm(-2) h(-1) respectively, and pharmacokinetic calculations indicated that therapeutic plasma concentrations are attainable for pediatric application.

Permeation of quinine across sublingual mucosa, in vitro.

Quinine is the first line treatment in severe P. falciparum malaria and nocturnal leg cramps and a fast, convenient delivery method of this drug quinine is needed. The purpose of this study was to investigate in vitro the sublingual route for the delivery of quinine. Permeation studies were carried out with Franz diffusion cells containing sublingual mucosa membranes with PBS receptor phase and dosed with solutions of quinine hydrochloride or quinine/2-hydroxypropyl-beta-cyclodextrin complexes. Receptor phase samples were taken 2 hourly over a 12h period and quinine was determined by reverse-phase HPLC analysis. The ventral surface of the tongue was significantly more permeable than porcine floor of the mouth (p<0.05) and there was no significant effect of freezing on the ventral surface of the tongue (p 0.2444). The presence of saliva caused a decrease in the permeation of quinine across the ventral surface of the tongue by up to 68%. Inclusion complexation between quinine and 2-HP-beta-CD was supported by (1)H NMR spectral data, and an ethanol vehicle provided the highest quinine flux from the inclusion complex solutions compared to deionised water and PEG. Overall, the data support further investigations into the clinical use of sublingual quinine, particularly for children with falciparum malaria or patients with nocturnal leg cramps. Use of quinine/cyclodextrin inclusion complexes may circumvent compliance issues due to bitter taste.