wz (2009), 39 «2y J. Kor. Pharm. Sci., Vol. 39, No. 2, 121-125 (2009) Intense Pulsed Light(IPL) w p v yá Á Á½ w w w (2009 3 25 Á2009 4 3 Á2009 4 10 ) 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, 151-742, 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)880-7870, E-mail : ddkim@snu.ac.kr 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
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 19.36 ±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, 250 4 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.
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 = 9197.4x 1081.5, r 2 = 0.9997). 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
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