The novel positively charged pro-drugs of NSAIAs in the general formulas (1, 2a, 2b, 2c, or 2d) “Structure 1, 2a, 2b, 2c, or 2d” were designed and synthesized. The compounds of the general formulas (1, 2a, 2b, 2c, or 2d) “Structure 1, 2a, 2b, 2c, or 2d” indicated above can be prepared from 
metal salts, 
organic base salts, or immobilized base salts of NSAIAs with suitable 
halide compounds. The positively charged amino groups in the pro-drugs in this invention largely increase the 
solubility of the drugs in water and will bond to the 
negative charge on the 
phosphate head group of membrane. Thus, the local concentration of the outside of the membrane or 
skin will be very high and will facilitate the passage of these pro-drugs from a region of 
high concentration to a region of low concentration. This bonding will disturb the membrane a little bit and may make some room for the lipophilic portion of the pro-
drug. When the molecules of membrane move, the membrane may “crack” a little bit due to the bonding of the pro-
drug. This will let the pro-
drug insert into the membrane. At pH 7.4, only about 99% of the amino group is protonated. When the amino group is not protonated, the bonding between the amino group of the pro-drug and the 
phosphate head group of the membrane will disassociate, and the pro-drug will enter the membrane completely. When the amino group of the pro-drug flips to the other side of the membrane and thus becomes protonated, then the pro-drug is pulled into the 
cytosol, a semi-liquid concentrated 
aqueous solution or suspension. These pro-drugs can be used for treating and preventing diabetes (type I or / and type II), abnormal blood glucose and lipid levels, 
stroke, heart 
attack, and other heart and vascular diseases Alzheimer's diseases, Parkinson's diseases and other neurodegenerative diseases, 
psoriasis, 
discoid lupus erythematosus, 
systemic lupus erythematosus (SLE), autoimmune 
hepatitis, 
multiple sclerosis (MS), and other autoimmune diseases, 
amyotrophic lateral sclerosis (ALS), oculopharyngeal 
muscular dystrophy (OPMD), and other 
muscle disorders, inflamed 
hemorrhoids, cryptitis, other inflammatory conditions of the anorectum, and pruritus ani, 
prostatitis, prostatocystitis, 
varicose veins, autoimmune liver 
inflammation, autoimmune 
kidney inflammation, 
vein inflammation and other inflammations, 
skin cancers, 
breast cancer, colon-
rectum cancer, oral 
cancer, and other cancers, 
scars, abnormal vascular 
skin lesions, birthmarks, moles (nevi), skin tags, aging spots (liver spots), and other skin disorders. These pro-drugs can be administered transdermally without the help of 
skin penetration enhancers.