Transdermal Delivery of Naltrexol and Skin Permeability Lifetime After Microneedle Treatment in Hairless Guinea Pigs

Overview

Journal J Pharm Sci

Publisher Elsevier

Specialties Pharmacology
Pharmacy

Date 2010 Feb 19

PMID 20166200

Citations 23

Authors

Stan L Banks

Raghotham R Pinninti

Harvinder S Gill

Kalpana S Paudel

Peter A Crooks

Nicole K Brogden

Mark R Prausnitz

Audra L Stinchcomb

Affiliations

Soon will be listed here.

Abstract

Controlled-release delivery of 6-beta-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.

Citing Articles

3D printing redefines microneedle fabrication for transdermal drug delivery.

Song K, Zhang W, Behzadfar M Biomed Eng Lett. 2024; 14(4):737-746.

PMID: 38946813 PMC: 11208358. DOI: 10.1007/s13534-024-00368-1.

Microneedle-Based Natural Polysaccharide for Drug Delivery Systems (DDS): Progress and Challenges.

Damiri F, Kommineni N, Ebhodaghe S, Bulusu R, Jyothi V, Sayed A Pharmaceuticals (Basel). 2022; 15(2).

PMID: 35215302 PMC: 8875238. DOI: 10.3390/ph15020190.

Microneedle for transdermal drug delivery: current trends and fabrication.

Jung J, Jin S J Pharm Investig. 2021; 51(5):503-517.

PMID: 33686358 PMC: 7931162. DOI: 10.1007/s40005-021-00512-4.

Design and Characterization of Spray-Dried Chitosan-Naltrexone Microspheres for Microneedle-Assisted Transdermal Delivery.

Ogunjimi A, Fiegel J, Brogden N Pharmaceutics. 2020; 12(6).

PMID: 32485999 PMC: 7355536. DOI: 10.3390/pharmaceutics12060496.

Characterization of Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System for Controlled and Extended Release of Ranibizumab.

Liu W, Borrell M, Venerus D, Mieler W, Kang-Mieler J Transl Vis Sci Technol. 2019; 8(1):12.

PMID: 30701127 PMC: 6350854. DOI: 10.1167/tvst.8.1.12.

References

McCaul M, Wand G, Rohde C, Lee S . Serum 6-beta-naltrexol levels are related to alcohol responses in heavy drinkers. Alcohol Clin Exp Res. 2000; 24(9):1385-91. View

Martanto W, Davis S, Holiday N, Wang J, Gill H, Prausnitz M . Transdermal delivery of insulin using microneedles in vivo. Pharm Res. 2004; 21(6):947-52. DOI: 10.1023/b:pham.0000029282.44140.2e. View

Paudel K, Nalluri B, Hammell D, Valiveti S, Kiptoo P, Hamad M . Transdermal delivery of naltrexone and its active metabolite 6-beta-naltrexol in human skin in vitro and guinea pigs in vivo. J Pharm Sci. 2005; 94(9):1965-75. DOI: 10.1002/jps.20398. View

Gill H, Prausnitz M . Coated microneedles for transdermal delivery. J Control Release. 2006; 117(2):227-37. PMC: 1853346. DOI: 10.1016/j.jconrel.2006.10.017. View

McAllister D, Wang P, Davis S, Park J, Canatella P, Allen M . Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci U S A. 2003; 100(24):13755-60. PMC: 283494. DOI: 10.1073/pnas.2331316100. View

Mark T, Coffey R, Vandivort-Warren R, Harwood H, King E . U.S. spending for mental health and substance abuse treatment, 1991-2001. Health Aff (Millwood). 2005; Suppl Web Exclusives:W5-133-W5-142. DOI: 10.1377/hlthaff.w5.133. View

Rukstalis M, Stromberg M, OBrien C, Volpicelli J . 6-beta-naltrexol reduces alcohol consumption in rats. Alcohol Clin Exp Res. 2000; 24(10):1593-6. View

Ferrari A, Bertolotti M, DellUtri A, AVICO U, Sternieri E . Serum time course of naltrexone and 6 beta-naltrexol levels during long-term treatment in drug addicts. Drug Alcohol Depend. 1998; 52(3):211-20. DOI: 10.1016/s0376-8716(98)00098-2. View

Kalia Y, Nonato L, Guy R . The effect of iontophoresis on skin barrier integrity: non-invasive evaluation by impedance spectroscopy and transepidermal water loss. Pharm Res. 1996; 13(6):957-60. DOI: 10.1023/a:1016081902162. View

10.

Mikszta J, Alarcon J, Brittingham J, Sutter D, Pettis R, Harvey N . Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery. Nat Med. 2002; 8(4):415-9. DOI: 10.1038/nm0402-415. View

11.

Sutinen R, Paronen P, Saano V, Urtti A . Water-activated, pH-controlled patch in transdermal administration of timolol. II. Drug absorption and skin irritation. Eur J Pharm Sci. 2000; 11(1):25-31. DOI: 10.1016/s0928-0987(00)00083-x. View

12.

Ferguson J, Martin C, Rayner C . Burn wound evaporation--measurement of body fluid loss by probe evaporimeter and weight change. Clin Phys Physiol Meas. 1991; 12(2):143-55. DOI: 10.1088/0143-0815/12/2/003. View

13.

Wall M, Brine D, PEREZ-REYES M . Metabolism and disposition of naltrexone in man after oral and intravenous administration. Drug Metab Dispos. 1981; 9(4):369-75. View

14.

Coulman S, Barrow D, Anstey A, Gateley C, Morrissey A, Wilke N . Minimally invasive cutaneous delivery of macromolecules and plasmid DNA via microneedles. Curr Drug Deliv. 2006; 3(1):65-75. DOI: 10.2174/156720106775197510. View

15.

HARWOOD H, Fountain D, Fountain G . Economic cost of alcohol and drug abuse in the United States, 1992: a report. Addiction. 1999; 94(5):631-5. DOI: 10.1080/09652149933450. View

16.

Stromberg M, Rukstalis M, Mackler S, Volpicelli J, OBrien C . A comparison of the effects of 6-beta naltrexol and naltrexone on the consumption of ethanol or sucrose using a limited-access procedure in rats. Pharmacol Biochem Behav. 2002; 72(1-2):483-90. DOI: 10.1016/s0091-3057(02)00721-9. View

17.

Wermeling D, Banks S, Hudson D, Gill H, Gupta J, Prausnitz M . Microneedles permit transdermal delivery of a skin-impermeant medication to humans. Proc Natl Acad Sci U S A. 2008; 105(6):2058-63. PMC: 2538880. DOI: 10.1073/pnas.0710355105. View

18.

Kaushik S, Hord A, Denson D, McAllister D, Smitra S, Allen M . Lack of pain associated with microfabricated microneedles. Anesth Analg. 2001; 92(2):502-4. DOI: 10.1097/00000539-200102000-00041. View

19.

De Costa B, Iadarola M, Rothman R, Berman K, George C, Newman A . Probes for narcotic receptor mediated phenomena. 18. Epimeric 6 alpha- and 6 beta-iodo-3,14-dihydroxy-17-(cyclopropylmethyl)-4,5 alpha-epoxymorphinans as potential ligands for opioid receptor single photon emission computed tomography: synthesis,.... J Med Chem. 1992; 35(15):2826-35. DOI: 10.1021/jm00093a016. View

20.

Meyer M, Straughn A, Lo M, Schary W, Whitney C . Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral administration. J Clin Psychiatry. 1984; 45(9 Pt 2):15-9. View