The stratum corneum (SC) is a primary barrier layer to defend against diffusion of exogenous substances through the skin.1 At least 15 factors are involved in percutaneous penetration, demonstrating the complexities of this process.2 In regards to skin and cosmetic care, elucidating factors involved in increasing absorption may be necessary to maximize their biologic effects.
Dermatologists have often recommended rubbing when applying topicals; however, quantitative studies to support its efficacy remain scarce, nor is there data on the effect of rubbing on cosmetic and skin care formulations. The available research suggests that rubbing can significantly affect absorption rates of some chemicals. Stronger evidence would help consumers confidently proceed with a skin care routine.
This overview sheds light on the enhancing effect of massage and the need for more in-depth investigation to specify the mechanisms of massage that can boost the efficacy of cosmetic and skin care ingredients.
Influencing dermal diffusion
Early research by McMaster et al. showed no influence of massage on cortisone cream dermal absorption in vivo following application to the naked retroauricular area of a guinea pig and the abdomen of a rhesus monkey.3 Amount absorbed over seven days was quantified using percent radioactivity in urine and normalized. While this method analyzes diffusion coefficients and excretion rates, it does not allow for quantifying concentration of chemical in skin.4 It is possible that the dosage was too small to notice any effect from rubbing.
Treffel et al. showed that the effect of pressure on absorption over 24 hours was only significant under high dose.5 Caffeine was applied to excised human skin at 0.25 bar over atmospheric pressure for 30 minutes. While there was no overall significant difference in flux for a 5µg/cm2 dose, flux of a 240µg/cm2 dose was 1.8 times higher under increased pressure conditions, showing that high pressure enhanced the rate of dermal penetration.
Flux rates reached a peak and then decreased quickly, suggesting that pressure works to increase SC filling rate.5 It is also possible that pressure increased transappendageal penetration because massage increases follicular penetration depth of liposomes, used as drug delivery systems, up to a factor of 5.6,7 This emphasizes a need to determine the pathways affected by rubbing and differentiate between the transepidermal and transappendageal pathways.
Ishii et al. studied skin permeation of another widely used corticoid, triamcinolone acetonide (TA), with white petrolatum ointment base ex vivo through hairless, male rat skin.8 Rubbing for 30 seconds at a pressure of 1.87-3.12N/cm2 was applied as a pretreatment. TA permeation after application of 1% TA ointment with a 1% TA ointment pretreatment was nine times higher than with a TA-free ointment pretreatment. Because conditions included rubbing either with or without TA, it seems that rubbing the drug itself into the skin effectively enhanced dermal penetration as opposed to simply rubbing the skin before drug application.
A previous study showed that sebum or skin lipids are extracted from skin surface into applied ointment, which increases TA solubility in ointment and permeability through skin.8,9 Not only does this demonstrate the need to consider interactions between sebum and topical ointments, it also indicates that the massage effect differs between hydrophilic and lipophilic substances.
Hasler-Nguyen and Fotopoulos studied ex vivo skin permeation of diclofenac-diethylamine 1.16% gel, using excised human skin.10 At eight hours, flux was five-fold higher with rubbing than without. However, no significant difference was detected after 24 hours.
Hui and Maibach investigated the massage effect on Reactive Skin Decontamination Lotion (RSDL), which partitions chemicals away from the skin and creates a neutralization reaction when in contact with the chemical.11,12 After contaminating excised human skin with radiolabelled paraoxon, RSDL was applied with or without rubbing for two minutes.11 Percent toxicant absorbed was quantified by counting radioactivity in skin and receptor fluid. Rubbing increased RSDL performance by a factor of 25; however, the mechanism and interactions affected remain unclear.
Affecting Skin Impedance
Ishii et al. also showed that skin impedance was a third lower after rubbing than without rubbing; thus indicating rubbing reduced skin barrier function.8 No ointment was used in testing skin impedance; however, the ointment itself increases skin impedance, so more evidence is needed to determine if decreasing skin barrier function was an important factor in increasing TA permeation after rubbing.
In addition, transcutaneous electrical resistance decreased about two-fold after application of diclofenac-diethylamine 1.16% gel with rubbing than without.10 Thus, rubbing may affect the skin barrier to facilitate penetration, possibly by affecting the skin’s lipid structure. Further investigation into the effect of massage in altering the skin layer is needed.
Increasing Cosmetic/Skin Care Ingredients Retained in Skin
According to Ishii, et al., depending on the specific rubbing experiment, there was a two- to three-fold increase in TA retained in full-thickness skin with rubbing than without.8 Further, in regards to cutaneous distribution of diclofenac, without rubbing, diclofenac diethylamine 1.16% gel remained in the outer skin layers, whereas with rubbing, the chemical penetrated deeper into the stripped skin.10 These experiments indicate that rubbing promotes a faster and deeper penetration into skin layers.
While these findings cannot be generalized to all skin care and cosmetic ingredients, they provide a basis and preliminary evidence suggesting that massage can be an important factor when treating skin. Its influence may be compounded by specific physiochemical properties of the chemical as well as the duration, pressure, and quantity of application. In the meantime, rubbing is just one of many variables influencing efficacy that await in-depth evaluation.
- RJ Scheuplein, Permeability of the skin: a review of major concepts, J. Invest. Dermato 67(5) 672-676 (1976)
- MA Ngo and HI Maibach, 15 factors of percutaneous penetration of pesticides, in Parameters for pesticide QSAR and PBPK/PD Models for Human Risk Assessment, Oxford University Press, Inc, Washington, DC USA (2012) pp 67-86
- J McMaster, HI Maibach, RC Wester, DAW Bucks, in Does rubbing enhance in vivo dermal absorption?, in Percutaneous Absorption, R Bronaugh and HI Maibach eds, Marcel Dekker, New York USA pp 359-361 (1985)
- H Schaefer, A Zesch, and G Stüttgen, Penetration, permeation, and absorption of triamcinolone acetonide in normal and psoriatic skin, Archives of Dermatological Research 258(3) 241-249 (1977)
- P Treffel, F Panisset, P Humbert, O Remoussenard, Y Bechtel, P Agache, Effect of pressure on in vitro percutaneous absorption of caffeine, Acta Derm Venereol 73 200-202 (1993)
- S Trauer, H Richter, J Kuntsche, R Buttemeyer, M Liebsch, M Linscheid, A Fahr, M Schafer-Koring, J Lademann, A Patzelt, Influence of massage and occlusion on the ex vivo skin penetration of rigid liposomes and invasomes EJPB 86 301-306 (2014)
- G Gregoriadis, Drug entrapment in liposomes, FEBS Letters 36(3) 292-296 1973
- H Ishii, H Todo, and K Sugibayashi. Effect of sebum and ointment rubbing on the skin permeation of triamcinolone acetonide from white petrolatum ointment, Biological and Pharmaceutical Bulletin 33(5) 876-880 2010
- H Ishii, H Todo, A Terao, T Hasegawa, M Akimoto, K Oshima, K Sugibayashi. Why does a hydrophilic drug permeate skin, although it is not soluble in white petrolatum?, Drug Dev. Ind. Pharm 35(11) 1356-1363 (2009)
- N Hasler-Nguyen and G Fotopoulos. Effect of rubbing on the in vitro skin permeation of diclofenac-diethylamine 1.16% gel. BMC Research Notes 5(1) 312-316 (2012)
- XY Hui XY and HI Maibach, Recent rubbing/decontamination data, University of California, San Francisco, Unpublished data.
- MD Schwartz, CG Hurst, MA Kirk, SJ Reedy, EH Braue, Jr, Reactive skin decontamination lotion (RSDL) for the decontamination of chemical warfare agent (CWA) dermal exposure, Curr Pharm Biotechnol 13(10) 1971-1979 (2012)