Translocation of cell penetrating peptide engrafted nanoparticles across skin layers.
Translocation of cell penetrating peptide engrafted nanoparticles across skin layers.
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DOI：
10.1016/j.biomaterials.2010.03.010
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发表时间：
2010-07
期刊：
影响因子：
14
通讯作者：
Singh MS
中科院分区：
文献类型：
--
作者：
Patlolla RR;Desai PR;Belay K;Singh MS
本研究的目的是评估细胞穿透肽（CPP）将脂质负载转运到皮肤层的能力。以Compritol、Miglyol和DOGS-NTA-Ni脂质为原料，采用热熔均质技术制备了荧光染料（DID-oil）包封的纳米脂质晶体纳米颗粒（FNLCN）。FNLCN表面包被TAT肽（FNLCNT）或对照YKA肽（FNLCNY），并使用Franz扩散细胞进行体外大鼠皮肤渗透研究。用共聚焦显微镜观察侧面皮肤切片，发现FNLCNT的皮肤渗透具有时间依赖性，24 h后，可观察到深度达120µm的荧光，并定位于毛囊和表皮。FNLCN和FNLCN配方主要在毛囊中观察到荧光。共聚焦拉曼光谱进一步支持了这一观察结果，FNLCNT处理皮肤在80和120µm深度处观察到更高的荧光信号强度，FNLCNT、FNLCN和FNLCNY处理皮肤切片的荧光峰强度分别为2:1:1和5:3:1。此外，用模型亲脂性药物塞来昔布（Cxb）替代DID-oil也显示出类似的结果，24 h后，CXBNT制剂比CXBN和CXBNY制剂分别使SC中的Cxb浓度增加3倍和6倍，表皮中的Cxb浓度增加2倍和3倍。我们的研究结果强烈表明，CPP可以将纳米颗粒及其有效载荷转移到更深的皮肤层。
The objective of the current study was to evaluate the ability of cell penetrating peptides (CPP) to translocate the lipid payload into the skin layers. Fluorescent dye (DID-oil) encapsulated nano lipid crystal nanoparticles (FNLCN) were prepared using Compritol, Miglyol and DOGS-NTA-Ni lipids by hot melt homogenization technique. The FNLCN surface was coated with TAT peptide (FNLCNT) or control YKA peptide (FNLCNY) and in vitro rat skin permeation studies were performed using Franz diffusion cells. Observation of lateral skin sections obtained using cryotome with a confocal microscope demonstrated that skin permeation of FNLCNT was time dependent and after 24 h, fluorescence was observed upto a depth of 120 µm which was localized in the hair follicles and epidermis. In case of FNLCN and FNLCNY formulations fluorescence was mainly observed in the hair follicles. This observation was further supported by confocal Raman spectroscopy where higher fluorescence signal intensity was observed at 80 and 120 µm depth with FNLCNT treated skin and intensity of fluorescence peaks was in the ratio of 2:1:1 and 5:3:1 for FNLCNT, FNLCN, and FNLCNY treated skin sections, respectively. Furthermore, replacement of DID-oil with celecoxib (Cxb), a model lipophilic drug showed similar results and after 24 h, the CXBNT formulation increased the Cxb concentration in SC by 3 and 6 fold and in epidermis by 2 and 3 fold as compared to CXBN and CXBNY formulations respectively. Our results strongly suggest that CPP can translocate nanoparticles with their payloads into deeper skin layers.
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