Liu Xingyu, Gao Changyou, Shen Jiacong, Möhwald Helmuth
Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Macromol Biosci. 2005 Dec 15;5(12):1209-19. doi: 10.1002/mabi.200500176.
A drug delivery system based on spontaneous deposition of soluble, low-molecular-weight therapeutic agents has been developed for the purpose of sustaining drug release. Layer-by-layer assembly of oppositely charged polyelectrolytes onto melamine formaldehyde (MF) colloidal particles, followed by removal of the cores at low pH has yielded intact hollow microcapsules having the ability to induce deposition of various water-soluble substances. Dynamic observation by confocal laser scanning microscopy provided direct evidence of such deposition. Dependence of loading rate on molecular weight was investigated. Efficient loading of an anti-cancer drug, daunorubicin (DNR), was confirmed by transmission electron microscopy (TEM). Its release was quantified by fluorometry. The results indicated that loading, and subsequent release, could be tuned by factors such as feeding concentrations, temperature, and salt concentrations. The intrinsic mechanism of loading and release was discussed taking into account the interaction between the drugs and the poly(styrene sulfonate)/MF complex existing in the hollow capsules. With culture of the HL-60 cell line, a kind of human leukemia cell, the presence of DNR-loaded capsules was seen to steadily decrease the cyto-viability. Fluorescence intensity averaged from inside the circles as a function of incubation time.
为实现药物的持续释放，开发了一种基于可溶性低分子量治疗剂自发沉积的药物递送系统。将带相反电荷的聚电解质逐层组装到三聚氰胺甲醛（MF）胶体颗粒上，然后在低pH值下去除核心，得到了能够诱导各种水溶性物质沉积的完整中空微胶囊。通过共聚焦激光扫描显微镜进行的动态观察提供了这种沉积的直接证据。研究了负载率对分子量的依赖性。通过透射电子显微镜（TEM）证实了抗癌药物柔红霉素（DNR）的有效负载。通过荧光测定法定量其释放。结果表明，负载以及随后的释放可以通过进料浓度、温度和盐浓度等因素进行调节。考虑到药物与中空胶囊中存在的聚（苯乙烯磺酸盐）/MF复合物之间的相互作用，讨论了负载和释放的内在机制。用一种人类白血病细胞系HL-60细胞进行培养时，发现负载DNR的胶囊的存在会使细胞活力稳步下降。圆圈内平均荧光强度作为孵育时间的函数。
