Brain-enhanced delivery of testosterone using a chemical delivery system complexed with 2-hydroxypropyl-beta-cyclodextrin.
Enhanced brain delivery of testosterone was suggested by application of a dihydropyridine in equilibrium pyridinium salt redox system. The drug delivery method is based upon the NAD+ in equilibrium NADH coenzyme system and utilizes the covalent attachment of testosterone to a dihydropyridine-type carrier. Upon administration of two such testosterone chemical delivery systems (T-CDS1 or T-CDS2), serum LH levels were suppressed by 71-87% after 24 hours and maintained through 5 days (28%) with T-CDS1. An equimolar dose of testosterone or testosterone propionate failed to suppress serum LH. Peripheral testosterone target tissues (seminal vesicles and prostate gland) were only slightly stimulated by T-CDS1. Complexation of T-CDS1 with 2-hydroxypropyl-beta-cyclodextrin allowed a lowering of the effective LH-suppressing dose of T-CDS1 from 25 mg/kg to 10 mg/kg, presumably by increasing the solubility of T-CDS1 in the blood. These findings suggest that testosterone can be effectively delivered to the central nervous system (CNS) with minimal peripheral effect, and the delivery of T-CDS1 to the CNS can be improved via complexation with 2-hydroxypropyl-beta-cyclodextrin.
Anderson
W R
WR
Department of Pharmacodynamics, University of Florida, Gainesville 32610.
Simpkins
J W
JW
Brewster
M E
ME
Bodor
N
N
D000818:Animals; D001812:Blood-Brain Barrier; D015195:Drug Design; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D009919:Orchiectomy; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*
D007202:Indicators and Reagents; D013739:Testosterone