Jeon Soha, Yoo Cha Young, Park Soo Nam
Department of Fine Chemistry, College of Energy and Biotechnology, Seoul National University of Science and Technology, 232, Gongneung-ro, Nowon-gu, Seoul 137-743, South Korea.
Department of Fine Chemistry, College of Energy and Biotechnology, Seoul National University of Science and Technology, 232, Gongneung-ro, Nowon-gu, Seoul 137-743, South Korea.
Colloids Surf B Biointerfaces. 2015 May 1;129:7-14. doi: 10.1016/j.colsurfb.2015.03.018. Epub 2015 Mar 14.
Layer-by-Layer (LbL) technology, based on the electrostatic interaction of polyelectrolytes, is used to improve the stability of drug delivery systems. In the present study, we developed multilayered liposomes with up to 10 alternating layers based on LbL deposition of hyaluronate-chitosan for transdermal delivery. Dihexadecyl phosphate was used to provide liposomes with a negative charge; the liposomes were subsequently coated with cationic chitosan (CH) followed by anionic sodium hyaluronate (HA). The resulting particles had a cumulative size of 528.28±29.22nm and an alternative change in zeta potential. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) revealed that the multilayered liposomes formed a spherical polyelectrolyte complex (PEC) after deposition. Observations in size distribution after 1 week found that the particles coated with even layers of polyelectrolytes, hyaluronate and chitosan (HA-CH), were more stable than the odd layers. Membrane stability in the presence of the surfactant Triton X-100 increased with an increase in bilayers as compared to uncoated liposomes. An increase in the number of bilayers deposited on the liposomal surface resulted in a sustained release of quercetin, with release kinetics that fit the Korsmeyer-Peppas model. In an in vitro skin permeation study, negatively charged (HA-CH)-L and positively charged CH-L were observed to have similar skin permeability, which were superior to uncoated liposomes. These results indicate that multilayered liposomes properly coated with polyelectrolytes of HA and CH by electrostatic interaction improve stability and can also function as potential drug delivery system for the transdermal delivery of the hydrophobic antioxidant quercetin.
基于聚电解质静电相互作用的层层（LbL）技术被用于提高药物递送系统的稳定性。在本研究中，我们基于透明质酸-壳聚糖的层层沉积开发了多达10个交替层的多层脂质体用于透皮给药。使用磷酸二己酯使脂质体带负电荷；随后脂质体用阳离子壳聚糖（CH）包被，接着用阴离子透明质酸钠（HA）包被。所得颗粒的累积尺寸为528.28±29.22nm，并且zeta电位有交替变化。差示扫描量热法（DSC）和透射电子显微镜（TEM）显示多层脂质体在沉积后形成了球形聚电解质复合物（PEC）。1周后对尺寸分布的观察发现，用偶数层聚电解质（透明质酸和壳聚糖，HA-CH）包被的颗粒比奇数层更稳定。与未包被的脂质体相比，在表面活性剂Triton X-100存在下的膜稳定性随着双层数量的增加而增加。脂质体表面沉积的双层数量增加导致槲皮素的持续释放，其释放动力学符合Korsmeyer-Peppas模型。在体外皮肤渗透研究中，观察到带负电荷的（HA-CH）-L和带正电荷的CH-L具有相似的皮肤渗透性，均优于未包被的脂质体。这些结果表明，通过静电相互作用用HA和CH的聚电解质适当包被的多层脂质体提高了稳定性，并且还可以作为疏水性抗氧化剂槲皮素透皮给药的潜在药物递送系统。
