title: Penetration depth, concentration and efficiency of transdermal α-arbutin delivery after ultrasound treatment with albumin-shelled microbubbles in mice.
abstract: Recently, the feasibility and effects of using microbubbles (MBs) as an ultrasound (US) contrast agent for enhancing the penetration in transdermal delivery in vivo have been demonstrated, but the mechanism and efficiency are unclear. This study demonstrates the penetration depth, concentration and efficiency of transdermal α-arbutin delivery during 4 weeks after US treatment with MBs in mice. Experimental animals were randomly divided into the following four groups (n = 5 animals per group): (1) penetrating α-arbutin alone (C), (2) US combined with penetrating α-arbutin, (3) US combined with MBs and penetrating α-arbutin, and (4) US combined with diluted MBs and penetrating α-arbutin (UBD). The penetration depths in agarose phantoms and pigskin were 47 and 84% greater for group UBD, respectively, than for group C. The in vitro skin penetration by 2% α-arbutin after 3 h was 83% greater in group UBD than in group C. The degree of in vivo skin whitening (quantified as the luminosity index) in group UBD significantly increased by 25% after 1 week, 34% after 2 weeks, and then stabilized after 3 weeks at 37% in C57BL/6J mice over a 4-week experimental period. Our results indicate that combined treatment with optimal US and MBs can increase skin permeability so as to enhance α-arbutin delivery to inhibit melanogenesis without damaging the skin in mice.
authors.affiliation: a Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology , Taipei , Taiwan , ROC.|b Department of Medical Engineering , National Defense Medical Center , Taipei , Taiwan , ROC.
authors.forename: Ai-Ho
authors.initials: AH
authors.lastname: Liao
authors.affiliation: a Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology , Taipei , Taiwan , ROC.
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Ma
authors.affiliation: c Department of Otolaryngology-Head and Neck Surgery , Tri-Service General Hospital, National Defense Medical Center , Taipei , Taiwan , ROC.|d Graduate Institute of Medical Sciences, National Defense Medical Center , Taipei , Taiwan , ROC.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Wang
authors.affiliation: e School of Pharmacy, National Defense Medical Center , Taipei , Taiwan , ROC , and.|f Bureau of Pharmaceutical Affairs, Military of National Defence Medical Affairs Bureau , Taipei , Taiwan , ROC.
authors.forename: Ming-Kung
authors.initials: MK
authors.lastname: Yeh
mesh_terms: D000279:Administration, Cutaneous; D000418:Albumins / Q000008:administration & dosage*; D000818:Animals; D001104:Arbutin / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D010539:Permeability; D012867:Skin / Q000378:metabolism*; D013552:Swine; D014465:Ultrasonics / Q000379:methods
chemical_list: D000418:Albumins; D001104:Arbutin
keywords: melanin; microbubbles; transdermal delivery; ultrasound; α-Arbutin