Novel polyoxyethylene esters of 18 beta-glycyrrhetic acid (GA) were synthesized and evaluated as potential dermal prodrugs. The permeation of these prodrugs (1(a-e)) was studied in-vitro, using excised human skin membranes (SCE; stratum corneum/epidermis) mounted in Franz type cells, and in-vivo, evaluating the ability of these compounds to inhibit methyl nicotinate (MN)-induced skin erythema in healthy human subjects. All the esters synthesized showed a good water stability, while the enzymatic hydrolysis rate was significantly affected by the length of the polyoxyethylenic chain used as promoiety. In in-vitro percutaneous absorption studies, only esters 1(b) and 1(c) (respectively triethylen- and tetraethylenglycol derivatives) showed an increased flux through SCE membranes compared with GA. Furthermore, we observed an appreciable and sustained in-vivo topical anti-inflammatory activity of esters 1(b) and 1c compared with the parent drug.
In-vitro and in-vivo evaluation of oligoethylene esters as dermal prodrugs of 18 beta-glycyrrhetic acid
PUGLIA, CARMELO;BONINA, Francesco Paolo
2006-01-01
Abstract
Novel polyoxyethylene esters of 18 beta-glycyrrhetic acid (GA) were synthesized and evaluated as potential dermal prodrugs. The permeation of these prodrugs (1(a-e)) was studied in-vitro, using excised human skin membranes (SCE; stratum corneum/epidermis) mounted in Franz type cells, and in-vivo, evaluating the ability of these compounds to inhibit methyl nicotinate (MN)-induced skin erythema in healthy human subjects. All the esters synthesized showed a good water stability, while the enzymatic hydrolysis rate was significantly affected by the length of the polyoxyethylenic chain used as promoiety. In in-vitro percutaneous absorption studies, only esters 1(b) and 1(c) (respectively triethylen- and tetraethylenglycol derivatives) showed an increased flux through SCE membranes compared with GA. Furthermore, we observed an appreciable and sustained in-vivo topical anti-inflammatory activity of esters 1(b) and 1c compared with the parent drug.File | Dimensione | Formato | |
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