Liu Ruihong, Sun Mingjing, Liu Xipan, Fan Aiping, Wang Zheng, Zhao Yanjun
Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, 92 Weijin Road, Tianjin 300072, China.
College of Science, Tianjin University of Science & Technology, 29 TEDA 13th Avenue, Tianjin 300457, China.
Int J Pharm. 2014 Feb 28;462(1-2):103-7. doi: 10.1016/j.ijpharm.2013.12.031. Epub 2013 Dec 25.
The objectives of this study were to generate novel thermo and pH dual responsive poly(amidoamine) (PAMAM) via precise surface engineering, and investigate the interplay of dendrimer stimuli-responsiveness and the loading and release properties of a model agent, vitamin E acetate (VEAc). A higher dendrimer generation and maximized VEAc loading at elevated pH all contributed to a lower cloud point (CP) of the dendrimer-VEAc complex. The drug loading in G3.5 surface-engineered PAMAM was 22 mol/mol (pH 7.0) and 10 mol/mol (pH 5.0), which corresponded to a complex CP value at ca. 13 °C (pH 7.0) and 46 °C (pH 5.0), respectively. At physiological conditions, only less than 40% of VEAc was liberated when reaching the plateau, whilst more than 90% of VEAc was released from such system within 6 h at pH 5.0. This was due to the transition of dendrimer surface from dehydrated state to hydrated state upon pH dropping, enabling rapid drug release for therapeutic action. This smart stimuli-responsive dendritic delivery system holds promise for the efficient drug delivery to tissues with pH abnormality such as tumor.
本研究的目的是通过精确的表面工程制备新型的热和pH双重响应性聚（酰胺胺）（PAMAM），并研究树枝状大分子的刺激响应性与模型药物维生素E醋酸酯（VEAc）的负载和释放特性之间的相互作用。更高代数的树枝状大分子以及在较高pH值下VEAc的最大负载量均导致树枝状大分子-VEAc复合物的浊点（CP）降低。在G3.5表面工程化的PAMAM中，药物负载量在pH 7.0时为22 mol/mol，在pH 5.0时为10 mol/mol，分别对应于约13°C（pH 7.0）和46°C（pH 5.0）的复合物CP值。在生理条件下，达到平台期时只有不到40%的VEAc被释放，而在pH 5.0时，超过90%的VEAc在6小时内从该系统中释放出来。这是由于pH值下降时树枝状大分子表面从脱水状态转变为水合状态，从而实现药物的快速释放以发挥治疗作用。这种智能的刺激响应性树枝状递送系统有望实现向肿瘤等pH异常组织的高效药物递送。
