Tocopheryl phosphate mixture (TPM) as a novel lipid-based transdermal drug delivery carrier: formulation and evaluation.
Transdermal drug delivery is a useful route of administration that avoids first-pass metabolism and more invasive delivery options. However, many drugs require enhancers to enable sufficient drug absorption to reach therapeutic effect. Alpha-tocopheryl phosphate (TP) and di-alpha-tocopheryl phosphate (T2P) are two phosphorylated forms of vitamin E which form tocopheryl phosphate mixture (TPM) when combined, and have been proposed to enhance the dermal and transdermal delivery of actives of interest. Here, we report the physicochemical characteristics and morphological properties of TPM formulations, including particle size, deformability and morphology, and its ability to facilitate the transport of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, and across, the skin. Results demonstrate that TPM self-assembles to form vesicular structures in hydroethanolic solutions ranging in mean size from 101 to 162 nM depending on the amount of TPM and ethanol present in the formulation. The ratio of TP to T2P in TPM formulations altered vesicle size and elasticity, with vesicles high in TP found to be more deformable than those rich in T2P. TPM produced a significant (p < 0.05) 2.4-3.4-fold increase in the absorption of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, or through, the skin. The TPM delivery platform was able to deliver a diverse range of actives with differing size and solubility profiles and therefore has significant potential to expand the number and types of drugs available for topical application and transdermal delivery.
Phosphagenics Limited, 11 Duerdin Street, Clayton, VIC, 3168, Australia. pgavin@phosphagenics.com.
Paul D
PD
Gavin
Phosphagenics Limited, 11 Duerdin Street, Clayton, VIC, 3168, Australia.
Mahmoud
M
El-Tamimy
Phosphagenics Limited, 11 Duerdin Street, Clayton, VIC, 3168, Australia.
Hooi Hong
HH
Keah
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal parade, Parkville, VIC, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, 381 Royal Parade, Parkville, VIC, 3052, Australia.
Ben J
BJ
Boyd
D000279:Administration, Cutaneous; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage / Q000737:chemistry; D002336:Carnosine / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002762:Cholecalciferol / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
D004337:Drug Carriers; C512375:alpha-di-tocopheryl phosphate; D014451:Ubiquinone; D002762:Cholecalciferol; C012552:alpha-tocopherol phosphate; D002110:Caffeine; D002336:Carnosine; C024989:coenzyme Q10; D024502:alpha-Tocopherol
Drug delivery; TPM; Tocopherol; Tocopheryl phosphate mixture; Transdermal; Vitamin E
J Control Release. 2012 Nov 28;164(1):26-40
23064010
J Control Release. 2000 Apr 3;65(3):403-18
10699298
Biochem Biophys Res Commun. 2004 May 21;318(1):311-6
15110789
Ther Deliv. 2015;6(9):1053-61
26458111
Methods Mol Biol. 2010;605:77-86
20072873
Biochim Biophys Acta. 1998 Jan 19;1368(2):201-15
9459598
Pharm Res. 2002 Jul;19(7):991-7
12180552
J Invest Dermatol. 2003 Aug;121(2):406-11
12880434
Pharm Res. 2004 Feb;21(2):201-30
15032302
Arch Biochem Biophys. 1992 Aug 1;296(2):575-82
1632644
Int J Nanomedicine. 2014 Jul 25;9:3539-50
25114524
Nutr Cancer. 1991;15(2):97-106
2038569
Pharmazie. 2007 Feb;62(2):133-7
17341034
Clin Exp Pharmacol Physiol. 2010 May;37(5-6):587-92
20082629
Int J Pharm. 2012 May 10;427(2):426-34
22310459
Free Radic Biol Med. 2005 Oct 1;39(7):970-6
16140216
Expert Opin Drug Deliv. 2006 Nov;3(6):727-37
17076595
J Pharm Pharmacol. 1999 Oct;51(10):1123-34
10579683
Drug Discov Today Technol. 2005 Spring;2(1):67-74
24981757
Ther Deliv. 2010 Jul;1(1):109-31
21132122
Biomaterials. 2006 Jan;27(2):271-80
16039711
Curr Drug Deliv. 2014;11(1):87-97
24533724
Annu Rev Nutr. 1996;16:321-47
8839930
Mol Pharm. 2013 Jun 3;10(6):2248-60
23587061
Int J Pharm. 2004 Feb 11;270(1-2):119-25
14726128
Br J Dermatol. 1998 Feb;138(2):207-15
9602862
Int J Pharm. 2010 Jun 15;392(1-2):304-10
20381599
AAPS J. 2012 Mar;14(1):10-8
22105442
Biochim Biophys Acta. 2008 Sep;1782(9):498-503
18555028
Eur J Pharm Biopharm. 2003 May;55(3):271-7
12754000
Nat Biotechnol. 2008 Nov;26(11):1261-8
18997767
J Control Release. 2005 Mar 2;103(1):123-36
15710506
Ann N Y Acad Sci. 2004 Dec;1031:405-11
15753182
Int J Pharm. 2006 Sep 28;322(1-2):60-6
16806755
Int J Pharm. 2000 Aug 25;204(1-2):159-69
11012000
Am Heart J. 1984 Jul;108(1):200-6
6731278
Int J Pharm. 2011 Jun 15;411(1-2):223-31
21458550
Crit Rev Ther Drug Carrier Syst. 2014;31(3):219-72
24940749