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STAR particles for enhanced topical drug and vaccine delivery
Nature Medicine ( IF 82.9 ) Pub Date : 2020-03-09 , DOI: 10.1038/s41591-020-0787-6
Andrew R Tadros 1 , Andrey Romanyuk 1 , Ian C Miller 2 , Andrea Santiago 2 , Richard K Noel 3 , Laura O'Farrell 3 , Gabriel A Kwong 2 , Mark R Prausnitz 1, 2
Affiliation  

Drug delivery to the skin is highly constrained by the stratum corneum barrier layer1. Here, we developed star-shaped particles, termed STAR particles, to dramatically increase skin permeability. STAR particles are millimeter-scale particles made of aluminum oxide or stainless steel with micron-scale projections designed to create microscopic pores across the stratum corneum. After gentle topical application for 10 s to porcine skin ex vivo, delivery of dermatological drugs and macromolecules, including those that cannot be given topically, was increased by 1 to 2 orders of magnitude. In mice treated with topical 5-fluorouracil, use of STAR particles increased the efficacy of the drug in suppressing the growth of subcutaneous melanoma tumors and prolonging survival. Moreover, topical delivery of tetanus toxoid vaccine to mice using STAR particles generated immune responses that were at least as strong as delivery of the vaccine by intramuscular injection, albeit at a higher dose for topical than intramuscular vaccine administration. STAR particles were well tolerated and effective at creating micropores when applied to the skin of human participants. Use of STAR particles provides a simple, low-cost and well-tolerated method for increasing drug and vaccine delivery to the skin and could widen the range of compounds that can be topically administered.



中文翻译:

用于增强局部药物和疫苗递送的 STAR 颗粒

皮肤的药物输送受到角质层屏障层的高度限制1. 在这里,我们开发了星形颗粒,称为 STAR 颗粒,以显着提高皮肤渗透性。STAR颗粒是由氧化铝或不锈钢制成的毫米级颗粒,具有微米级突起,旨在在角质层上形成微孔。在离体猪皮肤温和局部应用 10 秒后,皮肤病药物和大分子的递送,包括那些不能局部给药的药物,增加了 1 到 2 个数量级。在用局部 5-氟尿嘧啶治疗的小鼠中,使用 STAR 颗粒提高了药物抑制皮下黑色素瘤生长和延长生存期的功效。而且,使用 STAR 颗粒向小鼠局部递送破伤风类毒素疫苗产生的免疫反应至少与通过肌肉注射递送疫苗一样强,尽管局部给药的剂量高于肌内疫苗给药。当应用于人类参与者的皮肤时,STAR 颗粒具有良好的耐受性并能有效地产生微孔。STAR颗粒的使用为增加药物和疫苗向皮肤的递送提供了一种简单、低成本和耐受性良好的方法,并且可以扩大可以局部给药的化合物的范围。

更新日期:2020-03-09
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