Skin Lipid Synthesis Inhibition: A Possible Means for Enhancing Percutaneous Delivery of Levodopa

Kumar      Babita; Ashok   Kumar   Tiwary

doi:10.2174/1567201043334579

Abstract

Skin perturbation with ethanol followed by application of β-chloroalanine (β-CA) or atorvastatin (AVN) was employed for delaying the recovery of sphingosine (a precursor of ceramide) and cholesterol, respectively in epidermis of rats. Dose optimization studies revealed 600 μg of β-CA and 750 μg of AVN significantly (p < 0.05) inhibited the synthesis of sphingosine and cholesterol, respectively and prevented their replenishment to normal levels till 48 hr in viable rat skin. Co-application of calcium chloride (0.1 mM) inhibited the synthesis of both micro constituents of epidermis to a greater magnitude, whereas verapamil reduced this effect. The in vitro permeation of levodopa across treated skin portions was directly correlated with percentage of sphingosine and cholesterol inhibited by the treatments. The in vitro permeation of levodopa across skin excised after treatment with β-CA or AVN was enhanced 3-fold. Effective plasma concentration (1.58 μg / ml) of levodopa in rats was achieved within 2 hr and maintained till 12 hr after AVN treatment, and increased to 36 hr with the co-application of calcium chloride. However, when the skin was treated with β-CA, C eff was achieved after 4 hr and was maintained till 36 hr. The inclusion of calcium chloride maintained C eff for 48 hr. Hence, synthesis inhibition of skin lipids seems to offer a feasible means to enhance the systemic delivery of polar drugs like levodopa.

Keywords: skin sphingosine, cholesterol, chloroalanine, atorvastatin, percutaneous delivery, levodopa

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