Iontophoretic transdermal delivery using chitosan-coated PLGA nanoparticles for transcutaneous immunization
Iontophoretic transdermal delivery using chitosan-coated PLGA nanoparticles for transcutaneous immunization
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DOI：
10.1016/j.colsurfa.2020.125607
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发表时间：
2021-01-05
影响因子：
5.2
通讯作者：
Makino, Kimiko
中科院分区：
文献类型：
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作者：
Takeuchi, Issei;Suzuki, Takaaki;Makino, Kimiko
聚（DL-丙交酯-共-乙交酯）（PLGA）纳米粒子的经皮给药，使用离子电渗（IP）是有用的有效药物递送到毛囊。在这项研究中，我们研究了将其用于过敏原免疫治疗的可能性。以鸡卵清溶菌酶（HEL）为模型抗原。我们成功地制备了PLGA纳米粒子的平均体积直径为98.4 +/- 36.8 nm，使用反溶剂扩散法。PLGA纳米粒用壳聚糖羟丙基三甲基氯化铵包覆以屏蔽PLGA衍生的负电荷。表面电荷数密度计算为1.28 × 10（-2）M，证实颗粒具有正电荷。使用荧光标记的HEL进行树突状细胞的摄取试验。流式细胞仪检测结果表明，纳米颗粒载体的使用使平均荧光强度增加了5.6倍。使用腹部小鼠皮肤和Franz型扩散池（含和不含IP）进行离体皮肤蓄积研究。当IP应用于纳米颗粒时，小鼠皮肤中的HEL浓度比没有IP的高9.6倍，比HEL溶液高2.1倍。皮肤切片的图像证实了使用IP和纳米颗粒载体将HEL有效地递送到毛囊。在体内经皮免疫反应性研究中测定了HEL-specific IgG 1和IgG 2a滴度。在使用IP和纳米颗粒载体的测试开始后10周，HEL-specific IgG 1和IgG 2a滴度分别为7.4 x 10（4）和6.6 x 10（2）。两个值均高于皮下注射HEL溶液获得的值，表明IP和纳米颗粒载体联合使用的有效性。
Transdermal administration of poly(DL-lactide-co-glycolide) (PLGA) nanoparticles using iontophoresis (IP) is useful for efficient drug delivery to hair follicles. In this study, we investigated the possibility of using it in allergen immunotherapy. Hen egg-white lysozyme (HEL) was used as a model antigen. We successfully prepared PLGA nanoparticles with a mean volume diameter of 98.4 +/- 36.8 nm using an antisolvent diffusion method. The PLGA nanoparticles were coated with chitosan hydroxypropyltrimonium chloride to shield the PLGA-derived negative charge. The surface charge number density was calculated to be 1.28 x 10(-2) M, confirming that the particles had positive charges. An uptake test into dendritic cells was performed using fluorescently labeled HEL. The results of FACS measurement showed that the usage of the nanoparticle carrier increased the mean fluorescence intensity by 5.6 times. An ex vivo skin accumulation study was carried out using abdominal mouse skin and a Franz-type diffusion cell with and without IP. When IP was applied to the nanoparticles, the HEL concentration in mouse skin was 9.6 times higher than that without IP and 2.1 times higher than that of the HEL solution. Images of skin sections confirmed that HEL was efficiently delivered to hair follicles using IP and nanoparticle carriers. HEL-specific IgG1 and IgG2a titers were determined in an in vivo percutaneous immunoreactivity study. Ten weeks after the initiation of the test using IP and the nanoparticle carrier, HEL-specific IgG1 and IgG2a titers were 7.4 x 10(4) and 6.6 x 10(2), respectively. Both values were higher than those obtained by subcutaneous injection of HEL solution, indicating the effectiveness of the combined use of IP and nanoparticle carriers.