Vogt Annika, Combadiere Behazine, Hadam Sabrina, Stieler Karola M, Lademann Juergen, Schaefer Hans, Autran Brigitte, Sterry Wolfram, Blume-Peytavi Ulrike
Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Physiology, Charite-Universitätsmedizin Berlin, Berlin, Germany.
J Invest Dermatol. 2006 Jun;126(6):1316-22. doi: 10.1038/sj.jid.5700226.
Although conventional vaccines have generated major successes in the control of infectious diseases, several obstacles remain in their development against chronic diseases (HIV, tuberculosis), against which no current candidate vaccines yet ensure protection. The transcutaneous route of vaccine administration appears to be a promising approach of targeting vaccines toward antigen-presenting cells (APCs) and thus improving immune responses. We investigated the suitability of nanoparticles in this approach. We found a high density of Langerhans cells (LCs) around hair follicles that, when sorted, readily internalized all size particles. However, flow cytometry after transcutaneous application of 40, 750, or 1,500 nm nanoparticles on human skin samples revealed that only 40 nm particles entered epidermal LC. Fluorescence and laser scan microscopies, which were carried out to identify the penetration pathway of transcutaneously applied nanoparticles, revealed that only 40 nm particles deeply penetrate into vellus hair openings and through the follicular epithelium. We conclude that 40 nm nanoparticles, but not 750 or 1,500 nm nanoparticles, may be efficiently used to transcutaneously deliver vaccine compounds via the hair follicle into cutaneous APCs.
尽管传统疫苗在控制传染病方面取得了重大成功，但在开发针对慢性疾病（如艾滋病毒、结核病）的疫苗时仍存在一些障碍，目前尚无候选疫苗能确保对这些疾病提供保护。经皮接种疫苗似乎是一种将疫苗靶向抗原呈递细胞（APC）从而改善免疫反应的有前景的方法。我们研究了纳米颗粒在这种方法中的适用性。我们发现毛囊周围存在高密度的朗格汉斯细胞（LC），分选后的这些细胞能轻易内化所有尺寸的颗粒。然而，在人体皮肤样本上经皮应用40、750或1500纳米的纳米颗粒后进行的流式细胞术显示，只有40纳米的颗粒进入表皮LC。为确定经皮应用的纳米颗粒的渗透途径而进行的荧光和激光扫描显微镜检查显示，只有40纳米的颗粒能深入穿透毳毛开口并穿过毛囊上皮。我们得出结论，40纳米的纳米颗粒而非750或1500纳米的纳米颗粒，可能有效地用于经皮通过毛囊将疫苗化合物递送至皮肤APC。
