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1 wz (2009), 39 «2y J. Kor. Pharm. Sci., Vol. 39, No. 2, (2009) Intense Pulsed Light(IPL) w p v yá Á Á½ w w w ( Á Á ) Enhanced Topical Delivery of Arbutin using Intense Pulsed Light (IPL) Joon-Ho Choi, Suk-Jae Chung, Chang-Koo Shim and Dae-Duk Kim College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, , Korea (Received March 25, 2009ÁRevised April 3, 2009ÁAccepted April 10, 2009) ABSTRACT The objective of this study was to investigate the feasibility of applying the Intense Pulsed Light (IPL) as a tool to enhance the skin absorption of arbutin, a well-known skin-whitening agent. Arbutin solution or skin formulation was applied on the back of hairless mouse skin in vivo after IPL treatment, and then the skin deposition of arbutin was determined by HPLC. IPL treatment significantly increased the amount of arbutin in the skin after 6 hours when arbutin solution was applied 20 times. IPL also enhanced the skin deposition of arbutin when arbutin formulation was applied, although it was not significantly different. Significant increase of surface skin temperature was observed by IPL treatment, which might be a mechanism of the enhanced skin absorption of arbutin. These results suggest the feasibility of using IPL as a tool to increase the skin absorption of whitening agents, although further research needs to be conducted to understand its exact mechanism. Key words Arbutin, Topical delivery, Intense Pulsed Light (IPL) p(arbutin, hydroquinone-d-glucopyranside) glycosylated hydroquinone (Vaccinium spp.) š w. 1)» v tyrosinase y x x. ù w w» w v tv d melanocyte ¾ w w, p e (logp = 1.49) w p ƒ d m w melanocyte z» w»ƒ. v ƒ ƒ w ƒ ù y w w š., ƒ d» g, y, g v w ù, q w š. 2) p, w w v n w w Tel : 02) , [email protected] iontophoresis 3) š w x 4) mw n j eletrophoration w ƒ w z x. ù, iontophoresis v w ph y ƒ w v y k ƒ 5). w, q v w v ƒwš, - k v n ƒ j phonophoresis w š. w phonophoresis v y w x 6), iontophoresis yƒ v w ƒ š, n ¾ ƒ 5cm iontophoresis w û w, e w. 7,8), v w v n ƒ ù w ƒ w š. Intense pulsed light(ipl) ù q w wù xenon lamp 121

2 122 yá Á Á½ w q (400~1200 nm) Ÿ v w e» v j 3ƒ š : (1) û» target chromophore w 600~950 nm q w e w, 9) (2) x ü (oxy)hemoglobin target chromophore w 550~950 nm q w e w y, š 10,11) (3) tv s target chromophore w 400~700nm q w e w tv s e. 12,13) IPL v z w» w p w š IPL w p n hairless mouse w in vivo w. x»» p t t Sigma-Aldrich (St. Louis, MO, USA) w. v w» w p CNS( ) œ w. HPLC methanol acetonitrile Merck (Darmstadt, FRG) w z 0.2 µm vl wš w. Ÿ» CNS( ) œ Ÿ»(CNS Eosika-IPL, Seongnam, Korea) w š, v d w» w infrared thermometer (JT520C, Hansung, Korea) w. x Hairless mouse (, 25 ±5 g, Charles River Lab., USA) w w y k z w. IPL IPL v Crisscross ww. 14) Hairless mouse x wš l ƒ g. IPL w v v w» v w ƒ w r. IPL 1.5 cm 2.0 cm, q 450 nm ~1100 nm, r 900 msec, pulse duration 3.5 msec, energy fluence 2 12 J/cm š w. v ƒ» ¾ w w» w 8 10 w w. IPL z Hairless mouse v t d IPL» ww» w, IPL w» 10z y 20z w z hairless mouse v t infrared thermometer w d w. v ùkù t w d w. yw d w w s³ ƒ t w. Infrared thermometer d w 18 o C~500 o C. In vivo skin deposition of arbutin IPL 20z w z, 0.3 ml p y p k hairless mouse v (3.0 cm 2 =1.5cm 2.0 cm) š w. x, p w ±1.40 mg/ml, w p PBS w w. k k z v wš, p w ü z w PBS(pH 7.4) washing rinsing w v û w. z cotton swab v t g. v ƒ d cellophane adhesive tape(cuderm corporation, Dallas, USA) 20z strippingw z, 15) tape k (10mL) (2000 rpm) w ƒ d û p HPLC w. Stripping wš û tv vd z k (3 ml) ƒwš homogenizer (ULTRA-TURAXF T25 basic, IKA, Staufen, Germany) w w. (3000 rpm, 5 min)w û p HPLC w. p v w p HPLC w. Binary pump (Waters 515 HPLC Pump) auto-injector (Waters 717 plus Auto-sampler), UV-VIS detector (Waters 2487 Dual λ Absorbance Detector) Waters HPLC w. š Merck RP-8 column (LiChroCART, 5 µm, mm, Merck, Darmstadt, Germany) w š, Methanol water 15:85 yw w. q 280 nm, 0.7 ml/min w, 20 µl injection w š, retention time 6.2 min.

3 Intense Pulsed Light(IPL) w p v 123 Figure 2 Deposition of arbutin in the stratum corneum layer and the epidermis/dermis layers at 6 hours after applying arbutin solution on the hairless mouse skin in vivo. Each data represents the mean ± S.D. (n = 5). * : Significantly different from the control (without IPL treatment, p < 0.05). Figure 1 HPLC Chromatograms of arbutin (A) in the solution, (B) in the stratum corneum layer and (C) in the epidermis/dermis. m l mean±standard deviation (S.D.) x ùkü, p p w Student's t-test w. m w p- valueƒ 0.05 w» w. š p HPLC UV q 280 nm w, p w vj yw 0.5 ~ 100 µg/ml yw (y = x , r 2 = ). CNS œ p (Figure 1A), v ƒ (Figure 1B) tv/ v d (Figure 1C) p w (6.2 min), w vj ƒ. In vivo skin deposition studies of arbutin IPL ƒ óù z w» w v ƒ m w vd melanocyte ¾ w w v p d w v ƒ. IPL 20z w z, p v swš 6 w ƒ d tv / vd û p Figure 2 ùkü. IPL w š p sw w IPL w p deposition m w (p < 0.05)., IPL w p ƒ d ƒ ƒw š, w tv / vd wì ƒw ƒ. IPL 20z w z y t p w v swš v p d w Figure 3. IPL w š p w v sw control group w, ƒ d p e 2 4 z ƒ ù, 6 z IPL w m p e (Figure 3A)., tv vd e IPL w w ù, m (Figure 3B). w p PBS v w Figure 2 ew, p IPL

4 124 yá Á Á½ Figure 4 Surface temperature of hairless mouse skin after applying IPL 10 times or 20 times. Each data point represents the mean± S.D. (n = 3). * : Significantly different from the temperature before IPL (p<0.05). Figure 3 Deposition of arbutin (A) in the stratum corneum layer and (B) in the epidermis/dermis layers at 2, 4 and 6 hours after applying arbutin formulation on the hairless mouse skin in vivo. Each data represents the mean±s.d. (n = 5). * : Significantly different from the control (without IPL treatment, p < 0.05). w v ƒ. Effect of IPL irradiation on the skin temperature IPL w p v» ww» w IPL v t y d w Figure 4. IPL 10 w, v ù, 20 w v ƒ w. w, x IPL v ü j v e w. w, IPL e f x y x š ƒ w ù, v w w w v y e w. 16), IPL w p v f w ƒw., v ƒ w cholinesterase inhibitor VX v ƒ š ew. 17) p k z ùkü» tv v d w melanocyte tyrosinase ww. p z ùkü» w ƒ d n w zw s¾ w w. v e x, IPL w p v ü ƒ ƒw, v w w., IPL z v k ƒ w. ù, v t ƒ d v w ƒ w w ƒw. š x 1) D.K. Hincha, A.E. Oliver and J.H. Crowe, Lipid composition determines the effects of arbutin on the stability of membranes, Biophysical J., 77, (1999). 2) C.S. Yong, J.D. Rhee and H.G. Choi, Factors affecting percutaneous absorption, The J.S.B.R., 2, (2000).

5 Intense Pulsed Light(IPL) w p v 125 3) J.E. Riviere and M.C. Heit, Electrically-assisted transdermal drug delivery, Pharm. Res., 14, (1997). 4) R.H. Guy and J. Hadgraft, Transdermal Drug Delivery, Marcel Dekker, New York, U.S.A, (1989). 5) H.A. Ahn, Transdermal delivery of cationic drug, isopropamide through rat skin by iontophoresis, Thesis of Pharm. Seoul Nati. Univ., (1991). 6) P. Tyle and P. Agrawala, Drug delivery by phonophoresis, Pharmaceutical Research, 6, (1989). 7) S. Mitragotri, D. Blankschtein and R. langer, Transdermal drug delivery using low-frequency sonophoresis, Pharm. Res., 13, (1996). 8) D. Bommannan, H. Okuyama, P. Stauffer and R.H. Guy, Sonophoresis. I. The use of high-frequency ultrasound to enhance transdermal drug delivery, Pharm. Res., 9, (1992). 9) C. RaulinRaulin, S. Werner, W. Hartschuh and M.P. Schonermark, Effective treatment of hypertrichosis with pulsed light : a report of two cases, Ann. Plast. Surg., 39, (1997). 10) C.A. Schroeter and H.A. Neumann, An intense light source. The Photoderm VL-flashlamp as a new treatment possibliity for vascular skin lesions, Dermatol. Surg., 24, (1998). 11) M.P. Goldman, Treatment of benign vascular lesions with the Photoderm VL high-intensity pulsed light source, Adv. Dermatol., 13, (1997). 12) M.H. Gold, T.D. Foster and M.W. Bell, Nevus spilus successfully treated with an intense pulsed light source, Dermatol. Surg., 25, (1999). 13) G.A. Moreno Arias and J. Ferrando, Intense pulsed light for melanocytic lesions, Dermatol. Surg., 27, (2001). 14) J.M. Yarborough, Dermabrasion by wire brush, J. Dermatol. Surg. Oncol., 13, (1987). 15) H.M. Heise, L. Kupper and L.N. Butvina, Mid-infrared attenuated total reflection spectroscopy of human stratum corneum using a silver halide fiber probe of square crosssection and adhesive tape stripping, J. Mol. Struct., 661, (2003). 16) B. Friedrich, D. Michael, H. Ulrich, K. Roland, K. Gerd, K. Wolfgang, L. Michael, N. Reinhard, R. Christian and S. Nikolaus, Recommendations for medical and aesthetic treatment of the skin using laser or intense pulsed light (IPL) systems, Medical Laser Application, 20, (2008). 17) F.N. Craig, E.G. Cummings and V.M. Sim, Environmental temperature and the percutaneous absorption of a cholinesterase inhibitor VX, J. Invest. Dermatol., 68, (1977).

16(1)-3(국문)(p.40-45).fm

16(1)-3(국문)(p.40-45).fm w wz 16«1y Kor. J. Clin. Pharm., Vol. 16, No. 1. 2006 x w$btf3fqpsu'psn û w m w Department of Statistics, Chonnam National University Eunsik Park College of Natural Sciences, Chonnam National University