PROBLEM TO BE SOLVED: To design and synthesize a new NSAIA prodrug that is positively charged and can be administered transdermally.SOLUTION: A positively-charged NSAIA prodrug is designed and synthesized which has a chemical structure 1, 2a, 2b, 2c, or 2d. A positively-charged amino group of the prodrug greatly increases the solubility in water of the medicine, and thus bonds to a negative charge in a phosphate head group of a film. This bonding destabilizes the film a little and can make a little room in a lipophilic moiety of the prodrug, and in some cases, a slight crack may occur by the bonding of the prodrug. As a result, the prodrug comes to enter the film inside. At pH 7.4, about 99% of the amino groups are protonated. When the amino group is not protonated, the bonding between the amino group of the prodrug and the phosphate head group of the film dissociates, and hence the prodrug enters the film completely.SELECTED DRAWING: Figure 1
