Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Hyderabad 500037, India.
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
Int J Pharm. 2018 Oct 25;550(1-2):240-250. doi: 10.1016/j.ijpharm.2018.08.024. Epub 2018 Aug 27.
Topical delivery of siRNA is challenging task due to complex barrier property of stratum corneum and cationic lipid based carriers have been widely explored for this purpose due to improved permeation through skin. For gene delivery application, dendrimers are considered as efficient carrier due to their cationic nature and well-defined surface groups. However, they are not well explored for topical delivery. This work compares the suitability of PAMAM dendrimer with DOTAP liposome for topical delivery of siRNA against TNF-α. The particle size, zeta potential and entrapment efficiency of dendriplex were 99.80 ± 1.80 nm, 13.40 ± 4.84 mV and 98.72 ± 2.02% whereas for lipoplex were 174.80 ± 0.80 nm, 29.96 ± 0.51 mV and 94.99 ± 5.01% respectively. Both the formulations were stable in serum and in the presence of RNAse. TNF-α is inflammatory cytokine, hence the in vivo efficacy of developed formulations was determined using psoriatic plaque model. Results suggested improved phenotypic and histopathological features and reduced levels of IL-6, TNF-α, IL-17 and IL-22 for dendriplex and lipoplex treated groups in comparison to Imiquimod treated group. These findings suggest that dendrimer can be a potential carrier for topical gene delivery.
由于角质层的复杂屏障特性，siRNA 的局部递药是一项具有挑战性的任务，因此，由于经皮渗透得到改善，阳离子脂质载体已被广泛用于该目的。对于基因传递应用，由于其阳离子性质和明确的表面基团，树枝状聚合物被认为是有效的载体。然而，它们在局部递药方面的研究并不充分。这项工作比较了 PAMAM 树枝状聚合物与 DOTAP 脂质体用于局部递送针对 TNF-α 的 siRNA 的适用性。树枝状聚合物的粒径、Zeta 电位和包封效率分别为 99.80±1.80nm、13.40±4.84mV 和 98.72±2.02%，而脂质体的粒径、Zeta 电位和包封效率分别为 174.80±0.80nm、29.96±0.51mV 和 94.99±5.01%。两种制剂在血清中和 RNAse 存在下均稳定。TNF-α 是一种炎症细胞因子，因此，使用银屑病斑块模型确定了所开发制剂的体内疗效。结果表明，与咪喹莫特治疗组相比，树枝状聚合物和脂质体治疗组的表型和组织病理学特征得到改善，并且 IL-6、TNF-α、IL-17 和 IL-22 的水平降低。这些发现表明，树枝状聚合物可以成为局部基因传递的潜在载体。
