The clinical investigator

, Volume 72, Issue 12, pp 1086–1091 | Cite as

Liposomal tretinoin for uncomplicated acne vulgaris

  • M. Schäfer-Korting
  • H. C. Korting
  • E. Ponce-Pöschl
Clinical Pharmacology

Abstract

Frequently occurring skin irritancy and flare-up reactions impede the use of topical tretinoin for acne vulgaris due to poor patient compliance. Liposome encapsulation improves penetration into the skin and local tolerability in animals. We investigated efficacy and local tolerability of liposomal tretinoin in man. In a double-blind study 20 patients with uncomplicated acne vulgaris received liposomal tretinoin (0.01 %) on one side of the body and a commercial gel preparation with either 0.025% or 0.05% on the other once daily for 10 weeks. Comedones and papules/pustules were counted every 2 (−4) weeks. Then also redness, scaling, and burning were rated according to a four-point scale. Moreover, the patients noted skin irritancy in a diary on a daily base. With conventional tretinoin the gels were equally efficacious and equally well tolerated. Liposomal tretinoin also appeared equipotent to the reference gels. There may even have been a slightly more rapid clearing of comedones following the liposome preparation. With respect to skin irritancy, however, liposomal tretinoin was superior. As rated by the patients, liposome encapsulated tretinoin induced less burning (mean cumulative score 2.7 ± 1.2) than the 0.025% gel (16.1 ± 7.1) and the 0.05% gel (9.7±4.1) gel and less erythema (1.8±0.7) than the 0.025% gel (11.4 ± 3.8; (P < 0.05). Liposomal tretinoin was also better tolerated according to the rating by the investigator. Liposomal encapsulation of tretinoin allows reduction of the concentration of the active agent without a decline in efficacy for acne vulgaris. Since local tolerability is thus increased, liposomal tretinoin should favor the acceptance of this treatment by the patient.

Key words

Tretinoin Retinoic acid Liposomes Acne vulgaris Irritancy 

Abbreviations

SGOT

serum glutamate oxalacetate transaminase

SGPT

serum glutamate pyruvate transaminase

γGT

7-glutamyl transferase

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References

  1. 1.
    Amblard P, Basex J, Beurey J, Beylot C, Bonerandi JJ, Civatte J, Dupré A, Garrel J, Grupper C, Hincky M, Kalis B, Lambert D, Masse R, Meynadier J, Moulin G, Privat Y, Texier L, Geniaux M, Thivolet J, Verret JL (1982) AntibioAberel: efficaté, tolerance. Gazette Med 89:2193–2196Google Scholar
  2. 2.
    Eckstein E, Steiner H, Wesenberg W (1974) Zur externen Behandlung der Akne mit Tretinoin. Arzneimittelforschung 24:1205–1209Google Scholar
  3. 3.
    Egbaria K, Weiner N (1990) Liposomes as a topical drug delivery system. Adv Drug Delivery Systems 5:287–300Google Scholar
  4. 4.
    Foong WC, Harsanyi BB, Mezei M (1990) Biodisposition and histological evaluation of topically applied retinoic acid in liposomal, cream and gel dosage forms. In: Hanin I et al. (eds) Phospholipids. Plenum Press, New York, pp 279–282Google Scholar
  5. 5.
    Frosch, PJ (1985) Irritative und kontaktallergische Nebenwirkungen von Akne-Externa. Hautarzt 36 [Supp] 7]:179–180Google Scholar
  6. 6.
    Gesztes A, Mezei M (1988) Topical anesthesia of the skin by liposome-encapsulated tetracaine. Anesth Analg 67:1079–1081Google Scholar
  7. 7.
    Jacobs M, Martin GP, Marriott C (1988) Effects of phosphatidylcholine on the topical bioavailability of corticosteroids assessed by the human skin blanching assay. J Pharm Pharmacol 40:829–833Google Scholar
  8. 8.
    Juhlin L (1975) Topical vitamin A acid in acne vulgaris. Acta Dermatovenereol [Suppl] 74:133–134Google Scholar
  9. 9.
    Kligman AM, Grove GL, Hirose R, Leyden JJ (1986) Topical tretinoin for photoaged skin. J Am Acad Dermatol 15:856–859Google Scholar
  10. 10.
    Kligman AM, Mills OH, McGinley KJ, Leyden JJ (1975) Acne therapy with tretinoin in combination with antibiotics. Acta Derm Venereol Suppl 74:111–118Google Scholar
  11. 11.
    Korting HC, Braun-Falco O (1989) Efficacy and tolerability of combined topical treatment of acne vulgaris with tretinoin and erythromycin in general practice. Drugs Exp Clin Res 15:447–451Google Scholar
  12. 12.
    Korting HC, Zienicke H, Schafer-Korting M, Braun-Falco O (1990) Liposome encapsulation improves efficacy of betamethasone dipropionate in atopic eczema but not in psoriasis vulgaris. Eur J Clin Pharmacol 39:349–351Google Scholar
  13. 13.
    Korting HC, Schäfer-Korting M, Hart H, Laux P, Schmid M (1993) Anti-inflammatory activity of hamamelis distillate applied topically to the skin. Influence of vehicle and dose. Eur J Clin Pharmacol 44:315–318Google Scholar
  14. 14.
    Leyden JJ, Shalita AR (1986) Rational therapy for acne vulgaris: an update on topical treatment. J Am Acad Dermatol 15:907–914Google Scholar
  15. 15.
    Mahjour M, Mauser B, Rashidbaigi Z, Fawzi MB (1990) Effect of egg yolk lecithins and commercial soybean lecithins on in vitro skin permeation of drugs. J Controlled Release 14:243–252Google Scholar
  16. 16.
    Mandy SA, Thorne EG (1990) A comparison of the efficacy and safety of tretinoin cream 0.025% and 0.05%. Adv Ther 7:94–99Google Scholar
  17. 17.
    Masini V, Bonte F, Meybeck A, Wepierre J (1993) Cutaneous bioavailability in hairless rats of tretinoin in liposomes or gel. J Pharm Sci 82:17–21Google Scholar
  18. 18.
    Meybeck A, Bonte F, Redziniak G (1989) Improvement of comedolytic activity and tolerance of vitamin A acid in topical liposome formulations. 5th Congress of International Technological Pharmacy, Chatenay Malabry, France, pp 399–403Google Scholar
  19. 19.
    Mezei M (1993) Liposomes and the skin. In: Gregoriadis G et al (eds) Liposomes in drug delivery. Harwood, London, pp 125–135Google Scholar
  20. 20.
    Mills OH jr, Kligman AM (1978) Treatment of acne vulgaris with topically applied erythromycin and tretinoin. Acta Dermatovenereol 58:555–557Google Scholar
  21. 21.
    Nastruzzi C, Walde P, Menegatti E, Gambari R (1990) Liposome-associated retinoic acid. Increased in vitro antiproliferative effects on neoplastic cells. FEBS Lett 259:293–296Google Scholar
  22. 22.
    Papa CM (1975) The cutaneous safety of topical tretinoin. Acta Dermatovenereol Suppl 74:128–132Google Scholar
  23. 23.
    Patel HM (1985) Liposomes as controlled-release systems. Biochem Soc Trans 13:513–516Google Scholar
  24. 24.
    Patel HM, Moghimi SM (1993) Liposomes and the skin permeability barrier. In: Gregoriadis G et al (eds) Liposomes in drug delivery. Harwood, London, pp 137–148Google Scholar
  25. 25.
    Plewig G, Wolff HH, Braun-Falco O (1971) Lokalbehandlung normaler und pathologischer Haut mit Vitamin-ASäure. Arch Klin Exp Dermatol 239:390–413Google Scholar
  26. 26.
    Schafer-Korting M, Korting HC, Braun-Falco O (1989) Liposome preparations: a step forward in topical drug therapy for skin disease? J Am Acad Dermatol 21:1271–1275Google Scholar
  27. 27.
    Stiittgen G (1962) Zur Lokalbehandlung von Keratosen mit Vitamin-A-Säure. Dermatologica 124:65–80Google Scholar
  28. 28.
    Weiner N, Williams N, Birch G, Ramachandran C, Shipman C jr, Flynn G (1989) Topical delivery of liposomally encapsulated interferon evaluated in a cutaneous herpes guinea pig model. Antimicrob Agents Chemother 33:1217–1221Google Scholar
  29. 29.
    Weiss JS, Ellis CN, Headington JT, Tincoff T, Hamilton TA, Vorhees JJ (1988) Topical tretinoin improves photoaged skin. A double-blind vehicle controlled study. JAMA 259:527–532Google Scholar
  30. 30.
    Wester RC, Patel R, Nacht S, Leyden J, Melendres J, Maibach H (1991) Controlled release of benzoyl peroxide from a porous microsphere polymeric system can reduce topical irritancy. J Am Acad Dermatol 24:720–726Google Scholar
  31. 31.
    Winston MH, Shalita AR (1991) Acne vulgaris. Pathogenesis and treatment. Pediatr Clin North Am 38:889–903Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • M. Schäfer-Korting
    • 1
  • H. C. Korting
    • 2
  • E. Ponce-Pöschl
    • 3
  1. 1.Institut für PharmazieFreie Universität BerlinBerlinGermany
  2. 2.Dermatologische Klinik und PoliklinikLudwig-Maximilians-UniversitätMünchenGermany
  3. 3.Hautarzt-Praxis Dr. W. Klövekorn/Dr. E. Ponce-PöschlGilchingGermany

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