Fujimoto Takahiro, Wang Jian, Baba Kazuki, Oki Yuka, Hiruta Yuki, Ito Masayuki, Ito Shinobu, Kanazawa Hideko
Clinic F, Chiyoda, Tokyo, 1020083, Japan.
Faculty of Pharmacy, Keio University, Miato, Tokyo, 1050011, Japan.
Lasers Surg Med. 2017 Jul;49(5):525-532. doi: 10.1002/lsm.22616. Epub 2016 Dec 19.
Transdermal delivery of hydrophilic peptides remains a challenge due to their poor cellular uptake and transdermal penetration. We hypothesize that combination of a CO fractional laser to enhance percutaneous absorption and liposomes as transdermal carriers would improve skin penetration of hydrophilic drugs.
NA.
Liposomes were prepared using membrane fusion lipid dioleoylphosphatidylethanolamine, and used to deliver 5-carboxyfluorescein (CF) and fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as model hydrophilic peptide drugs. Liposome size was estimated by dynamic light scattering. Liposome uptake into murine macrophage cells and penetration or permeation into Yucatan micropig skin after irradiation by CO fractional laser at varying energy levels (laser power and exposure duration) were investigated using Franz cell and fluorescence microscopy. Oxidative damage to the irradiated mouse skin was assessed by electron spin resonance.
Size of CF and OVA-FITC encapsulated liposomes was 324 ± 75 nm. Cellular uptake of OVA-FITC delivered by liposomes was 10-fold higher (1,370 relative fluorescence units, RFU) than delivered in solution form (130 RFU). Fractional laser irradiation increased skin permeation rate of CF liposomes (0-10%) and OVA-FITC liposomes (4-40%) in a dose-dependent manner. Although peeling off the stratum corneum facilitated CF liposome penetration at low energy levels (2.69-3.29 J/cm ; 10-20 W for 500 μs), drug permeation was similar (7-8%) in peeled or untreated skin at higher laser energy levels (6.06 J/cm ; 20 W for 1,500 μs). FITC penetrated deeper in the skin after laser irradiation. However, OH, O2-, and VC reactive oxygen species were generated upon irradiation of the skin with a fractional CO laser.
Increasing laser power and irradiation, time increased liposome uptake by cells and penetration of peptide drugs across the skin in a dose-dependent manner. High-energy CO fractional laser overcomes the rate-limiting barrier function of the stratum corneum. Further investigations are required to establish the safety and efficacy of fractional laser-irradiation assisted delivery of liposome-encapsulated drugs as a transcutaneous drug delivery system. Lasers Surg. Med. 49:525-532, 2017. © 2016 Wiley Periodicals, Inc.
由于亲水性肽的细胞摄取和经皮渗透较差，其经皮递送仍然是一个挑战。我们假设，联合使用二氧化碳分数激光增强经皮吸收以及脂质体作为经皮载体，将改善亲水性药物的皮肤渗透。
无。
使用膜融合脂质二油酰磷脂酰乙醇胺制备脂质体，并用于递送5-羧基荧光素（CF）和异硫氰酸荧光素偶联的卵清蛋白（OVA-FITC）作为亲水性肽类药物模型。通过动态光散射估计脂质体大小。使用弗兰兹扩散池和荧光显微镜研究在不同能量水平（激光功率和照射持续时间）的二氧化碳分数激光照射后，脂质体对小鼠巨噬细胞的摄取以及对尤卡坦微型猪皮肤的渗透情况。通过电子自旋共振评估照射对小鼠皮肤的氧化损伤。
包裹CF和OVA-FITC的脂质体大小为324±75纳米。脂质体递送的OVA-FITC的细胞摄取量（1370相对荧光单位，RFU）比溶液形式递送的摄取量（130 RFU）高10倍。分数激光照射以剂量依赖方式增加了CF脂质体（0 - 10%）和OVA-FITC脂质体（4 - 40%）的皮肤渗透率。尽管在低能量水平（2.69 - 3.29 J/cm²；500微秒内10 - 20瓦）下剥除角质层有助于CF脂质体渗透，但在较高激光能量水平（6.06 J/cm²；1500微秒内20瓦）下，剥除或未处理的皮肤中的药物渗透率相似（7 - 8%）。激光照射后FITC在皮肤中渗透更深。然而，二氧化碳分数激光照射皮肤时会产生活性氧物质OH、O₂⁻和VC。
增加激光功率和照射时间会以剂量依赖方式增加细胞对脂质体的摄取以及肽类药物的皮肤渗透。高能量二氧化碳分数激光克服了角质层的限速屏障功能。需要进一步研究以确定分数激光照射辅助递送脂质体包裹药物作为经皮给药系统的安全性和有效性。《激光外科与医学》49:525 - 532，2017。© 2016威利期刊公司
