Topical delivery of 5-fluorouracil (5-FU) by 3-alkylcarbonyloxymethyl-5-FU prodrugs
| Autor: | William J. Roberts, Kenneth B. Sloan |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Stereochemistry
Skin Absorption Pharmaceutical Science In Vitro Techniques Administration Cutaneous Medicinal chemistry Mice Structure-Activity Relationship chemistry.chemical_compound Drug Delivery Systems medicine Animals Transition Temperature Prodrugs Isopropyl myristate Diffusion cell Transdermal Mice Hairless Myristates Chemistry Prodrug Solubility Fluorouracil Mouse skin Solvents Female Delivery system Epidermis Immunosuppressive Agents medicine.drug |
| Zdroj: | Journal of Pharmaceutical Sciences. 92:1028-1036 |
| ISSN: | 0022-3549 |
| DOI: | 10.1002/jps.10382 |
| Popis: | The 3-alkylcarbonyloxymethyl-5-fluorouracil (3-ACOM-5-FU) prodrugs have been characterized by their solubilities in isopropyl myristate (S(IPM)) and partition coefficients between IPM and pH 4.0 buffer (K(IPM:AQ)). Estimated S(AQ) values have been obtained from S(AQ) = S(IPM)/K(IPM:AQ.) The abilities of the prodrugs to deliver total 5-FU species from IPM suspensions through hairless mouse skin (J(i)) have been evaluated in diffusion cell experiments. All of the prodrugs were much more soluble in IPM than 5-FU, and the propionyloxymethyl (C2) member of the series was almost twice as soluble in pH 4.0 buffer. Except for the acetyloxymethyl (C1) member of the series, the 3-ACOM-5-FU prodrugs exhibited greater S(IPM) and S(AQ) values than the corresponding 1-alkylcarbonyloxymethyl (1-ACOM-5-FU) prodrugs. The 3-ACOM-5-FU prodrugs that exhibited greater S(IPM) and S(AQ) values than the 1-ACOM-5-FU prodrugs also exhibited greater J(i) values, except for the C2 member. The C2 member also gave the largest error in predicting J(i) using the transformed Potts-Guy equation. All of the 3-ACOM-5-FU prodrugs delivered more 5-FU as a percentage of J(i) than the 1-ACOM-5-FU prodrugs but were not more effective as a series at targeting dermal as opposed to transdermal delivery. |
| Databáze: | OpenAIRE |
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