title: Interplay of stimuli-responsiveness, drug loading and release for a surface-engineered dendrimer delivery system.
abstract: 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.
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, 92 Weijin Road, Tianjin 300072, China.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Liu
authors.affiliation: College of Science, Tianjin University of Science & Technology, 29 TEDA 13th Avenue, Tianjin 300457, China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Sun
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, 92 Weijin Road, Tianjin 300072, China.
authors.forename: Xipan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, 92 Weijin Road, Tianjin 300072, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Fan
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, 92 Weijin Road, Tianjin 300072, China. Electronic address: wangzheng2006@tju.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, School of Pharmaceutical Science & Technology, Tianjin University, 92 Weijin Road, Tianjin 300072, China. Electronic address: zhaoyj@tju.edu.cn.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D014810:Vitamin E
keywords: Controlled release; Dendrimers; Dendrimer–drug interactions; Stimuli-responsive; Surface-engineering