Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs

Stan L. Banks; Raghotham R. Pinninti; Harvinder S. Gill; Kalpana S. Paudel; Peter A. Crooks; Nicole K. Brogden; Mark R. Prausnitz; Audra L. Stinchcomb

doi:10.1002/jps.22083

Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs

Stan L. Banks, Raghotham R. Pinninti, Harvinder S. Gill, Kalpana S. Paudel, Peter A. Crooks, Nicole K. Brogden, Mark R. Prausnitz, Audra L. Stinchcomb

Chemical Engineering

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

Controlled-release delivery of 6-β-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. MN pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6-fold enhancement in steady-state plasma concentration was observed in vivo with MN treated skin with NTXOL·HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible nonlipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application.

Original language	English
Pages (from-to)	3072-3080
Number of pages	9
Journal	Journal of Pharmaceutical Sciences
Volume	99
Issue number	7
DOIs	https://doi.org/10.1002/jps.22083
State	Published - Jul 2010

Keywords

6-β-naltrexol
Addiction therapy
Hairless guinea pig
Microneedle
Transdermal

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@article{5013dd382d6e4ebcb9eaeddc90d18963,

title = "Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs",

abstract = "Controlled-release delivery of 6-β-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. MN pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6-fold enhancement in steady-state plasma concentration was observed in vivo with MN treated skin with NTXOL·HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible nonlipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application.",

keywords = "6-β-naltrexol, Addiction therapy, Hairless guinea pig, Microneedle, Transdermal",

author = "Banks, {Stan L.} and Pinninti, {Raghotham R.} and Gill, {Harvinder S.} and Paudel, {Kalpana S.} and Crooks, {Peter A.} and Brogden, {Nicole K.} and Prausnitz, {Mark R.} and Stinchcomb, {Audra L.}",

note = "Funding Information: We would like to thank Dr. Mark Allen at Georgia Tech for the use of his microfabrication facilities. This research was supported in part by NIH R01DA13425 and R01EB006369. H.S.G. and M.R.P. are members of the Center for Drug Design, Development and Delivery and the Institute for Bioengineering and Bioscience at Georgia Tech. M.R.P. is the Emerson Lewis Faculty Fellow.",

year = "2010",

month = jul,

doi = "10.1002/jps.22083",

language = "English",

volume = "99",

pages = "3072--3080",

journal = "Journal of Pharmaceutical Sciences",

issn = "0022-3549",

number = "7",

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TY - JOUR

T1 - Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs

AU - Banks, Stan L.

AU - Pinninti, Raghotham R.

AU - Gill, Harvinder S.

AU - Paudel, Kalpana S.

AU - Crooks, Peter A.

AU - Brogden, Nicole K.

AU - Prausnitz, Mark R.

AU - Stinchcomb, Audra L.

N1 - Funding Information: We would like to thank Dr. Mark Allen at Georgia Tech for the use of his microfabrication facilities. This research was supported in part by NIH R01DA13425 and R01EB006369. H.S.G. and M.R.P. are members of the Center for Drug Design, Development and Delivery and the Institute for Bioengineering and Bioscience at Georgia Tech. M.R.P. is the Emerson Lewis Faculty Fellow.

PY - 2010/7

Y1 - 2010/7

N2 - Controlled-release delivery of 6-β-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. MN pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6-fold enhancement in steady-state plasma concentration was observed in vivo with MN treated skin with NTXOL·HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible nonlipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application.

AB - Controlled-release delivery of 6-β-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. MN pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6-fold enhancement in steady-state plasma concentration was observed in vivo with MN treated skin with NTXOL·HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible nonlipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application.

KW - 6-β-naltrexol

KW - Addiction therapy

KW - Hairless guinea pig

KW - Microneedle

KW - Transdermal

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DO - 10.1002/jps.22083

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AN - SCOPUS:77951443813

SN - 0022-3549

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SP - 3072

EP - 3080

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

IS - 7

ER -

Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs

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