Development of Novel Formulations to Enhance in Vivo Transdermal Permeation of Tocopherol
Open accessAbstract
Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobicity and large molecular mass. The aim of the present study was to develop alpha-tocopherol (T) topical formulations and evaluate their ex vivo and in vivo permeation. Franz diffusion cells were used for ex vivo permeation, and neonatal rats were used for in vivo permeation. Seven gel formulations and 21 liquid formulations were investigated for physical stability, viscosity and permeation of T. Analysis of T was performed by a validated HPLC method using a UV detector. The ex vivo permeation from gel and emulsion formulations was very poor (0.001-0.015%). Highest permeation was observed from monophasic liquid formulations containing dimethyl sulfoxide (DMSO), tocopheryl polyethylene glycols (TPGs), propylene glycol, ethanol and 9.5% T. The in vivo results demonstrated higher retention in the epidermis compared to subcutaneous tissues, 1377 and 1.13 μg g⁻¹, respectively. Increasing T concentration from 4.8 to 9.5% did not increase the amount permeated or % of T retained. It was concluded that simple solutions of T in the presence of DMSO and TPGs were more promising systems for effective transdermal permeation compared to gel, emulsion or oleaginous systems.
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The transdermal permeation of α-tocopherol is particularly challenging due to its high hydrophobicity and large molecular mass.
“The transdermal permeation of α‐tocopherol is particularly challenging due to its high hydrophobicity and large molecular mass [16].”
From Microencapsulated α‐Tocopherol and Moringa Extract for Improved Skin Protection: Insights From Human Skin Assessment in Cosmetic Formulations (2025) · cites this paper as [16]
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Cites
Oxidative Stress and Its Role in Skin Disease
Trouba, K. J., Hamadeh, H. K., Amin, R. P., & Germolec, D. R. (2002) · Antioxidants & Redox Signaling · doi:10.1089/15230860260220175 · Cited by 277 · see citing works
Gabbanini, S., Matera, R., Beltramini, C., Minghetti, A., & Valgimigli, L. (2010) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2010.01.029 · Cited by 25 · see citing works
Flagged first, then by citations
Research works printed but not linked: 23
- W. Ting, C. Vest and R. Sontheimer, Review of traditional and novel modalities that enhance the permeability of local therapeutics across the stratum corneum, Int. J. Dermatol. 43 (2004) 538-547; DOI: 10.1111/j.1365-4632.2004.02147.x. · DOI
- M. B. Brown, G. P. Martin, S. A. Jones and F. K. Akomeah, Dermal and transdermal drug delivery systems: current and future prospects, Drug Deliv. 13 (2006) 175-187; DOI: 10.1080/10717540500455975. · DOI
- A. A. Date and V. B. Patravale, Microemulsions: applications in transdermal and dermal delivery, Crit. Rev. Ther. Drug Carrier Syst. 24 (2007) 547-596; DOI: 10.1615/CritRevTherDrugCarrierSyst.v24. i6.20. · DOI
- A. Tavakkol, Z. Nabi, N. Soliman and T. G. Polefka, Delivery of vitamin E to the skin by a novel liquid skin cleanser: Comparison of topical versus oral supplementation, J. Cosmet. Sci. 55 (2004) 177-187; PMID 15131729.
- X. Wang and P. J. Quinn, The location and function of vitamin E in membranes (review), Mol. Membr. Biol.17 (2000) 143-156; DOI: 10.1080/09687680010000311. · DOI
- J. J. Thiele, C. Schroeter, S. N. Hsieh, M. Podda and L. Packer, The antioxidant network of the stratum corneum, CurrProblDermatol. 29 (2001) 26-42; DOI: 10.1159/000060651. · DOI
- F. Nachbar and H. C. Korting, The role of vitamin E in normal and damaged skin, J. Mol. Med. 73 (1995) 7-17; DOI: 10.1007/BF00203614. · DOI
- F. Marra, C. Ostacolo, S. Laneri, A. Bernardi and P. Santi, Synthesis, hydrolysis, and skin retention of amino acid esters of alpha-tocopherol, J. Pharm. Sci. 98 (2009) 2364-2376; DOI: 10.1002/jps.21608. · DOI
- M. Rangarajan and J. L. Zatz, Effect of formulation on the delivery and metabolism of alpha-to- copheryl acetate, J. Cosmet. Sci. 52 (2001) 225-236; PMID 11479655.
- A. C. Williams and B.W. Barry, Penetration enhancers, Adv. Drug Deliv. Rev. 56 (2004) 603-618; DOI: 10.1016/j.addr.2003.10.025. 299-309. · DOI
- S.R. Pinnell. Cutaneous photodamage, oxidative stress, and topical antioxidant protection, J. Am. Acad. Dermatol. 48 (2003) 1-19; DOI: 10.1067/mjd.2003.16. · DOI · Paper page
- J. C. Tsai, R. H. Guy, C. R. Thornfeldt, W. N. Gao, K. R. Feingold and P. M. Elias. Metabolic ap- proaches to enhance transdermal drug delivery. 1. Effect of lipid synthesis inhibitors, J. Pharm.Sci. 85 (1996) 643-648; DOI: 10.1021/js950219p. · DOI
- P. M. Elias, K. R. Feingold and J. C. Tsai, Metabolic Approach to Transdermal Drug Delivery, in Trans- dermal Drug Delivery (Eds. R.H. Guy, J. Hadgraft), 2 nd ed. Marcel Dekker, New York 2003, pp. 285-383; DOI: 10.1007/978-3-642-00477-3_13. · DOI
- B. Godin and E. Touitou, Ethosomes: New prospects in transdermal delivery, Crit. Rev. Ther. Drug Carrier Syst. 20 (2003) 63-102; DOI: 10.1615/CritRevTherDrugCarrierSyst.v20.i1.20. · DOI
- E. Yenilmez, E. BaŞaran and Y. Yazan, Release characteristics of vitamin E incorporated chitosan microspheres and in vitro-in vivo evaluation for topical application, Carbohyd. Polym. 84 (2011) 807-811; DOI: 10.1016/j.carbpol.2010.07.002. · DOI
- A. Niestroj, Comparison of methods for calculation of the partition coefficients of selected tocoph- erols, J. Planar. Chromatogr. 20 (2007) 483-486; DOI: 10.1556/JPC.20.2007.6.15. · DOI
- H. Mahamongkol, R. A. Bellantone, G. Stagni and F. M. Plakogiannis, Permeation study of five formulations of alpha-tocopherol acetate through human cadaver skin, J. Cosmet. Sci. 56 (2005) 91-103; DOI: 10.1111/j.0142-5463.2005.00275_4.x. · DOI
- A. Nada, Y. S. R. Krishnaiah, A. Zaghloul and I. Khattab, In vitro and in vivo permeation of vita- min E and vitamin E acetate from cosmetic formulations, Med. Princ. Pract. 20 (2011) 509-513; DOI: 10.1159/000329883. · DOI
- R. Cassano, S. Trombino, R. Muzzalupo, L. Tavano and N. Picci, A novel dextran hydrogel linking trans-ferulic acid for the stabilization and transdermal delivery of vitamin E, Eur. J. Pharm. Bio- pharm. 72 (2009) 232-238; DOI: 10.1016/j.ejpb.2008.10.003. · DOI
- B. Rozman, M. Gosenca, M. Gasperlin, K. Padois and F. Falson, Dual influence of colloidal silica on skin deposition of vitamins C and E simultaneously incorporated in topical microemulsions, Drug Dev. Ind. Pharm. 36 (2010) 852-860; DOI: 10.3109/03639040903541187. · DOI
- A. Nada, Y. S. R. Krishnaiah, A. Zaghloul and I. Khattab, Analysis of vitamin E in commercial cosmetic preparations by HPLC, J. Cosmet. Sci. 61 (2010) 353-365; PMID 20939975.
- K. Zhao and J. Singh, In vitro percutaneous absorption enhancement of propranolol hydrochlo- ride through porcine epidermis by terpenes/ethanol, J. Control. Release 62 (1999) 359-366; DOI: 10.1016/S0168-3659(99)00171-6. · DOI
- N. Aggarwal, S. Goindi and S. D. Mehta, Preparation and evaluation of dermal delivery system of griseofulvin containing vitamin E-TPGS as penetration enhancer, AAPS Pharm. Sci. Tech. 13 (2012) 67-74; DOI: 10.1208/s12249-011-9722-y. · DOI
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Pinto, F., de Barros, D. D., & Fonseca, L. (2018) · Industrial crops and products (Print) · doi:10.1016/j.indcrop.2018.03.042 · Cited by 70
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Saez, V. M., de Souza, I. D. L., & Mansur, C. R. E. (2018) · International Journal of Cosmetic Science · doi:10.1111/ics.12452 · Cited by 83 · see citing works
“Liposomes [8, 9], polymeric micro and nanospheres [10–12], nanoemulsions [13, 14], transdermal devices [15, 16] and lipid nanoparticles (NPs) [17, 18] are some examples.”
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Karim, M., Boikess, R., Schwartz, R. A., & Cohen, P. (2022) · Archives of Dermatological Research · doi:10.1007/s00403-022-02494-1 · Cited by 46
Akhtar, N., Akhtar, N., Menaa, F., Alharbi, W., Alaryani, F. S., Alqahtani, A., & Ahmad, F. (2022) · Gels · doi:10.3390/gels8060335 · Cited by 45
“, skin conditioning agents, humectants, anti-aging solutions) to prevent transepidermal water (TEWL/TWL) loss and aging [9].”
BackgroundInfluentialTop weapons in skin aging and actives to target the consequences of skin cell senescence
Draelos, Z. D., Bogdanowicz, P., & Saurat, J. ‐. (2024) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.19648 · Cited by 46 · see citing works
Akhtar, N., & Akhtar, N. (2022) · Journal of Cosmetic Dermatology · doi:10.1111/jocd.14907 · Cited by 31
Bozza, A., Marengo, A., Camisassa, E., Valsania, M. C., Ugazio, E., Benetti, E., Guglielmo, S., Argenziano, M., Pisani, M., Sereno, A., et al. (2025) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2025.125233 · Cited by 7 · see citing works
Todaria, M., & Awasthi, R. (2026) · BioNanoScience · doi:10.1007/s12668-025-02369-5 · Cited by 6 · see citing works
“The trans-membrane diffusion kinetics of FA and KMP was evaluated by analyzing the cumulative amount of drug permeated (Q) in the receptor compartment at predetermined intervals up to 6 h [41].”
Maloney, D., Zhang, J., Bhargava, S., Hogan, M. V., & Wang, J. H. (2024) · Bioanalysis · doi:10.1080/17576180.2024.2412438 · Cited by 5 · see citing works
Kessler, J. C., Martins, I. M., Manrique, Y. A., Gudjónsdóttir, S. D., Rodrigues, A. E., Barreiro, M. F., & Dias, M. M. (2025) · Journal of Cosmetic Dermatology · doi:10.1111/jocd.70486 · Cited by 4 · see citing works
de França, B. M., Ghasemishahrestani, Z., de Souza, G. D., da Silva, R. N., Queiroz, D. D., Pierre, M. R., Pereira, M., Forero, J. S. B., & Corrêa, R. J. (2020) · Photochemistry and Photobiology · doi:10.1111/php.13335 · Cited by 3
“for TPPy in the permeation/retention skin assay since primary studies obtained similar solubility for other drugs in this vehicle (41,42).”
MethodComparative ex vivo and in vitro Permeation Kinetics of Tocopherol in Liquid Formulations
Nada, A. (2018) · doi:10.22377/ajp.v12i01.2043 · Cited by 3
“The animals were euthanized using carbon dioxide asphyxiation before experiments, and the epidermis was removed by a heat separation technique as described in our previous study.[4] The entire skin of neonate rats was soaked in water at 60°C for 60 s, followed by careful removal of the epidermis.”
BackgroundMethodResultInfluentialSelf-citationRegenthal, R., & Abraham, G. (2023) · Research in Veterinary Science · doi:10.1016/j.rvsc.2023.05.005 · Cited by 1 · see citing works
- Authors
- Nada, A. H., Zaghloul, A. A., Hedaya, M. M., & Khattab, I. S.
- Affiliations
- Kuwait University (KW)
- Department of Pharmaceutics Faculty of Pharmacy Kuwait University, Kuwait
- ORCID
- Nada, Aly H.
- Venue
- Acta Pharmaceutica
- Publisher
- Walter de Gruyter GmbH
- Published
- 2014-09-01
- Volume
- 64
- Issue
- 3
- Pages
- 299-309
- ISSN
- 1330-0075 (ISSN-L)
- 1846-9558
- OpenAlex
- W2080585692
- Cited by
- 13
- References
- 33
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2020: 1 · 2018: 3
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Acta Pharmaceutica (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Hrčak Portal of scientific journals of Croatia (University Computing Centre) (submittedVersion, other-oa)
- Funders
- Kuwait University
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- tocopherols, alpha-tocopherol, transdermal permeation, topical formulation, dimethyl sulfoxide, propylene glycol, ethanol, gel formulation, emulsion formulation, skin retention, ex vivo permeation, physical stability
- MeSH terms
- Administration, Cutaneous, Ethanol, Animals, Animals, Newborn, Antioxidants, Chemistry, Pharmaceutical, Chromatography, High Pressure Liquid, Drug Stability, Emulsions, Gels, Models, Biological, Permeability, Polyethylene Glycols, Polymers, Propylene Glycols, Skin, Skin Absorption, Spectrophotometry, Ultraviolet, Technology, Pharmaceutical, Viscosity, Rats, Sprague-Dawley, alpha-Tocopherol, Hydrophobic and Hydrophilic Interactions
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