Dexamethasone prodrug

MRXSOl/lipid shell + dexamethasone prodrug Ultrasound-activated drug delivery [83]... 

Numerous reports of prodrugs in the literature show improved drug effects. Prodrugs that have shown some measure of success for site-specific delivery include L-3,4-dihydroxyphenylalanine (L-dopa) to the brain [56], dipivaloyl derivative of epinephrine to the eye [57], /-glutamyl-L-dopa to the kidney [58], fi-n-glucoside dexamethasone and prednisolone derivatives to the colon [59], thiamine-tetrahydrofuryldisulfide to red blood cells, and various amino acid derivatives of antitumor agents such as daunorubicin [61,62], acivicin [63], doxorubicin [63], and phenylenediamine [63] to tumor cells. 

The same strategy was applied in colon-specific delivery of two corticosteroids used to treat inflammatory bowel disease [20][21], Indeed, budeso-nide /3-D-glucuronide and dexamethasone /3-D-glucuronide underwent ready hydrolysis in the luminal contents of rat colon and caecum. Rat mucosal homogenates were less active, and hydrolysis in human fecal samples was quite low. Based on these and other studies, the prodrugs were found to be suitable candidates for delivery of corticosteroids to the large intestine. 

Synthetic glucocorticoids are prednisolone, prednisone, methylprednisolone, dexamethasone, betamethasone and triamcinolone (Table 13.2). Hydrocortisone is available as either succinate or phosphate salts for oral and intravenous administration. It is the drug of choice when a rapid effect is required, e.g. acute adrenal insufficiency, or as peri-operative replacement therapy. Prednisolone can also be given intravenously. It has about 0.8 of the mineralocorticoid activity of hydrocortisone. Prednisone is a prodrug that is converted to prednisolone in the body. For chronic therapy, synthetic steroids without mineralocorticoid activity are preferred, such as dexamethasone, betamethasone or triamcinalone. Beclo-metasone passes membranes poorly and is more active topically than when given orally. It is used as an aerosol for chronic rhinitis and asthma, and topically in severe eczema. Fludrocortisone is a synthetic halogenated derivate of cortisol that is used for its mineralocorticoid effect. 

Abiraterone is the newest of the steroid synthesis inhibitors to enter clinical trials. It blocks 17a-hydroxylase (P450cl7) and 17,20-lyase (Figure 39-1), and predictably reduces synthesis of cortisol and gonadal steroids in the adrenal and gonadal steroids in the gonads. A compensatory increase occurs in ACTH and aldosterone synthesis, but this can be prevented by concomitant administration of dexamethasone. Abiraterone is an orally active steroid prodrug and has been studied in the treatment of refractory prostate cancer. 

Limclhason Dexamethasone palmitate (prodrug) Green Cros. i. Japan Chronic rheumaioid arthritis... 

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