Projects and Grants per year
Grants and Contracts Details
Description
Alcoholism and opiate addiction lead to major health-related problems and societal costs for people in the
United States and the rest of the world as well. Therefore, research and development for improved
pharmacologic treatments for drug and alcohol abuse are very important. Naltrexone, an opioid antagonist,
is currently used in oral tablet form to help maintain opioid addicts in a drug-free state. Most recently,
naltrexone has been indicated as an adjunct in the treatment of alcohol dependence, as well as reported to
reduce alcohol craving in certain alcoholic populations. Transdermal delivery of naltrexone is desirable for
opioid addicts and alcoholics in order to help reduce side effects associated with oral therapy and improve
compliance. Naltrexone itself does not have the essential physicochemical properties that would allow a
therapeutic dose of the drug to cross the human skin barrier. We plan to continue designing and
synthesizing prod rugs, which are more skin permeable than naltrexone, in order to make a therapeutically
successful drug delivery system. We hypothesize that prod rugs of naltrexone and prod rugs in combination
with microneedle treatment will improve the transdermal delivery rate of naltrexone, and that these prodrugs
will make excellent research tools for investigating quantitative structure-permeability relationships (QSPR)
for transdermal flux and optimization of flux in combination with microneedle enhancement. These
prodrugs/microneedles should improve naltrexone delivery rates across the skin because of optimized
physicochemical properties for faster diffusion. The specific aims of this project include: (1) to synthesize a
series of naltrexone and naltrexol (active metabolite) prodrugs designed to elucidate fundamental aSPRs for
transdermal flux optimization with and without microneedle use, (2) to characterize the physicochemical
parameters of the drugs, including molecular weight, molecular volume, lipophilicity, hydrogen-bonding
potentials, melting points, heats of fusion, and solubilities in select solvents, (3) to measure the drugs'
penetration and concurrent bioconversion through human skin in vitro with and without microneedle use, and
(4) to characterize the pharmacokinetics of the drugs in guinea pigs in vivo with and without microneedle
use. Correlation of our in vitro data with the in vivo model will aid in the creation of a reliable aSPR database
for transdermal prod rugs with and without microneedle use, as well as help to identify the most promising
orodrua/microneedle system for eventual human use.
Status | Finished |
---|---|
Effective start/end date | 7/1/00 → 3/31/12 |
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Projects
- 1 Finished
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Naltrexone Prodrugs for Transdermal Delivery Supplement
Stinchcomb, A. (PI) & Crooks, P. (CoI)
7/1/00 → 3/31/12
Project: Research project