量化纳米颗粒在猪耳和人体前臂毛囊中的摄取。

Quantification of nanoparticle uptake into hair follicles in pig ear and human forearm.

机构信息

Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.

Philipps University Marburg, Pharmaceutical Technology and Biopharmacy, Marburg, Germany.

出版信息

J Control Release. 2014 Apr 10;179:25-32. doi: 10.1016/j.jconrel.2014.01.018. Epub 2014 Jan 29.

DOI:10.1016/j.jconrel.2014.01.018

PMID:24486055

Abstract

Drug delivery via the hair follicle (HF) especially with nanoparticles (NP) recently gained attention due to a depot effect and facilitated absorption conditions within the lower HF. With the prospect of transdermal drug delivery, it is of interest to optimize the follicular uptake of NP. In this study, a method was developed to quantify NP uptake into HF and applied in vitro in a pig ear model and in vivo in human volunteers. The influence of NP material on HF uptake was investigated using fluorescence-labeled NP based on poly(D,L-lactide-co-glycolide) (PLGA). All NP had similar hydrodynamic sizes (163-170 nm) but different surface modifications: (i) plain PLGA, (ii) chitosan-coated PLGA (Chit.-PLGA), and (iii) Chit.-PLGA coated with different phospholipids (PL) (DPPC (100), DPPC:Chol (85:15), and DPPC:DOTAP (92:8). Differential stripping was performed, including complete mass balance. The samples were extracted for fluorescence quantification. An effect of the PL coating on follicular uptake was observed as DPPC (100) and DPPC:DOTAP (92:8) penetrated into HF to a higher extent than the other tested NP. The effect was observed both in the pig ear model as well as in human volunteers, although it was statistically significant only in the in vitro model. An excellent in vitro-in vivo correlation (IVIVC, r(2)=0.987) between both models was demonstrated, further supporting the suitability of the pig ear model as a surrogate for the in vivo situation in humans for quantifying NP uptake into HF. These findings may help to optimize NP for targeting the HF and to improve transdermal delivery.

摘要

经毛囊（HF）给药，尤其是通过纳米颗粒（NP）给药，由于存在库效应以及较低 HF 内促进吸收的条件，最近受到了关注。鉴于经皮给药的前景，优化 NP 对 HF 的摄取具有重要意义。在这项研究中，开发了一种方法来量化 NP 进入 HF 的摄取，并在猪耳模型的体外和人体志愿者的体内进行了应用。使用基于聚（D，L-丙交酯-共-乙交酯）（PLGA）的荧光标记 NP 研究了 NP 材料对 HF 摄取的影响。所有 NP 的水动力尺寸（163-170nm）相似，但表面修饰不同：（i）PLGA 原载物，（ii）壳聚糖包被的 PLGA（Chit.-PLGA），和（iii）用不同磷脂（PL）包被的 Chit.-PLGA（DPPC（100），DPPC:Chol（85:15）和 DPPC:DOTAP（92:8））。进行了差分剥离，包括完整的质量平衡。对样品进行荧光定量提取。观察到 PL 涂层对毛囊摄取的影响，因为 DPPC（100）和 DPPC:DOTAP（92:8）比其他测试的 NP 更深入地渗透到 HF 中。该效应在猪耳模型以及人体志愿者中均观察到，尽管仅在体外模型中具有统计学意义。两种模型之间表现出极好的体外-体内相关性（IVIVC，r(2)=0.987），进一步支持猪耳模型作为人体体内情况的替代模型，用于定量 NP 对 HF 的摄取。这些发现可能有助于优化 NP 以靶向 HF，并改善经皮递送。