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
Current Drug Delivery
Title: Skin Lipid Synthesis Inhibition: A Possible Means for Enhancing Percutaneous Delivery of Levodopa
Volume: 1 Issue: 4
Author(s): Kumar Babita and Ashok Kumar Tiwary
Affiliation:
Keywords: skin sphingosine, cholesterol, chloroalanine, atorvastatin, percutaneous delivery, levodopa
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.
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Cite this article as:
Babita Kumar and Tiwary Kumar Ashok, Skin Lipid Synthesis Inhibition: A Possible Means for Enhancing Percutaneous Delivery of Levodopa, Current Drug Delivery 2004; 1 (4) . https://dx.doi.org/10.2174/1567201043334579
DOI https://dx.doi.org/10.2174/1567201043334579 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
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