Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan; Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba 283-8555, Japan.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan.
Colloids Surf B Biointerfaces. 2022 Dec;220:112916. doi: 10.1016/j.colsurfb.2022.112916. Epub 2022 Oct 12.
The effect of transcutaneous immunization was studied using a combined system of poly(DL-lactide-co-glycolide) (PLGA) nanoparticles and iontophoresis (IP). Both hen egg-white lysozyme (HEL)-loaded PLGA nanoparticles coated with chitosan hydroxypropyltrimonium chloride and their fluorescent nanoparticles were prepared using an antisolvent diffusion method. Their mean volume diameters were 87.6 ± 38.9 nm and 84.9 ± 27.6 nm, respectively. It was suggested from the results of the ex vivo skin accumulation study using fluorescent nanoparticles that the HEL released from the nanoparticles to the skin surface was efficiently delivered to antigen-presenting cells. HEL-specific IgG1 and IgG2a titers were determined in an in vivo percutaneous immunoreactivity study using lysozyme-sensitized mice. As results, the group using nanoparticles and IP showed 1.33 times higher HEL-specific IgG1 titer than a sham treatment group. The HEL-specific IgG2a titer was 1.36 times higher in the nanoparticles and IP group than in the HEL solution and IP group. It was suggested from the quantification results of total IgE in serum that the combined use of PLGA nanoparticles and IP reduced the total IgE concentration. The level of cytokines may have decreased due to Th1 cell activation and relative suppression of Th2 cells. The cytokine level is presumed to be reduced by activation of Th1 cells and relative suppression of Th2 cells. The histamine amount in plasma and rectal temperature after the induction of anaphylactic shock using lysozyme-sensitized mice were also studied, which indicates that the combined use of PLGA nanoparticles and IP may provide the same therapeutic effect as an injection.
经皮免疫的效果研究采用了聚（DL-乳酸-共-乙醇酸）（PLGA）纳米粒子和离子电渗（IP）的联合系统。壳聚糖羟丙基三甲基氯化铵包覆的载有鸡卵清白蛋白溶菌酶（HEL）的 PLGA 纳米粒子及其荧光纳米粒子均采用反溶剂扩散法制备。它们的平均体积直径分别为 87.6±38.9nm 和 84.9±27.6nm。从使用荧光纳米粒子的体外皮肤累积研究结果表明，从纳米粒子释放到皮肤表面的 HEL 被有效地递送到抗原呈递细胞。使用卵清白蛋白致敏小鼠的体内经皮免疫活性研究中测定了 HEL 特异性 IgG1 和 IgG2a 滴度。结果，使用纳米粒子和 IP 的组的 HEL 特异性 IgG1 滴度比假处理组高 1.33 倍。纳米粒子和 IP 组的 HEL 特异性 IgG2a 滴度比 HEL 溶液和 IP 组高 1.36 倍。从血清中总 IgE 的定量结果表明，PLGA 纳米粒子和 IP 的联合使用降低了总 IgE 浓度。细胞因子水平可能因 Th1 细胞的激活和 Th2 细胞的相对抑制而降低。细胞因子水平的降低可能是由于 Th1 细胞的激活和 Th2 细胞的相对抑制。还研究了使用卵清白蛋白致敏小鼠诱导过敏休克后血浆中的组胺量和直肠温度，表明 PLGA 纳米粒子和 IP 的联合使用可能提供与注射相同的治疗效果。
