Topical Skin Cancer Therapy Using Doxorubicin-Loaded Cationic Lipid Nanoparticles and Iontophoresis
Topical Skin Cancer Therapy Using Doxorubicin-Loaded Cationic Lipid Nanoparticles and Iontophoresis
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DOI：
10.1166/jbn.2015.2139
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发表时间：
2015-11-01
影响因子：
2.9
通讯作者：
Lopez, Renata F. V.
中科院分区：
文献类型：
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作者：
Huber, Lucas A.;Pereira, Tatiana A.;Lopez, Renata F. V.
局部给予化疗药物是治疗皮肤癌的一种有前途的方法；然而，需要不同的药物策略才能使大量药物渗透肿瘤。这项工作检验了负载阿霉素的阳离子固体脂质纳米粒子 (DOX-SLN) 的阳极离子电渗疗法增加 DOX 的分布和肿瘤渗透的潜力。制备并表征了由脂质硬脂酸和单油酸甘油酯和新型 BODIPY 染料组成的双标记阳离子 DOX-SLN。分别使用共焦显微镜和垂直扩散池在体外评估 DOX 的皮肤分布和渗透性。通过阳极离子电渗疗法在裸 BALB/c 小鼠诱导的鳞状细胞癌中评价 DOX-SLN 的体内抗肿瘤潜力。 DOX 的封装极大地改变了 DOX 分配系数并增加了 DOX 在角质层 (SC) 脂质基质中的分布。与离子电渗疗法的结合在皮肤毛囊中产生了高浓度药物储存区。尽管 DOX 溶液的离子电渗疗法使 DOX 在活表皮中的渗透增加了约 4 倍，但阳离子 DOX-SLN 的离子电渗疗法使 DOX 的渗透增加了约 50 倍。在体内，DOX-SLN 离子电渗疗法可有效抑制肿瘤细胞的存活。肿瘤生长并伴随着角化的增加和随后的细胞死亡。这些结果表明离子电渗疗法与 DOX-SLN 具有强大的协同作用，并为皮肤癌的治疗提供了潜在的策略。
The topical administration of chemotherapeutics is a promising approach for the treatment of skin cancer; however, different pharmaceutical strategies are required to allow large amounts of drug to penetrate tumors. This work examined the potential of the anodic iontophoresis of doxorubicin-loaded cationic solid lipid nanoparticles (DOX-SLN) to increase the distribution and tumor penetration of DOX. A double-labeled cationic DOX-SLN composed of the lipids stearic acid and monoolein and anew BODIPY dye was prepared and characterized. The skin distribution and penetration of DOX were evaluated in vitro using confocal microscopy and vertical diffusion cells, respectively. The antitumor potential was evaluated in vivo through the anodic iontophoresis of DOX-SLN in squamous cell carcinoma induced in nude BALB/c mice. The encapsulation of DOX drastically altered the DOX partition coefficient and increased the distribution of DOX in the lipid matrix of the stratum corneum (SC). The association with iontophoresis created high-concentration drug reservoir zones in the follicles of the skin. Although the iontophoresis of a DOX solution increased the penetration of DOX in the viable epidermis by approximately 4-fold, the iontophoresis of cationic DOX-SLN increased the DOX penetration by approximately 50-fold. In vivo, the DOX-SLN iontophoretic treatment was effective in inhibiting tumor cell survival and. tumor growth and was accompanied by an increase in keratinization and consequent cell death. These results indicate a strong and synergic effect of iontophoresis with DOX-SLN and provide a potential strategy for the treatment of skin cancer.