title: Macromolecular crowding of molecular imprinting: A facile pathway to produce drug delivery devices for zero-order sustained release.
abstract: This paper reported the facile fabrication of drug delivery devices for zero-order sustained release by molecular crowding strategy of molecularly imprinting technology. Crowding-assisted molecularly imprinting polymers (MIPs) matrices were prepared by free-radical precipitation polymerization using aminoglutethimide (AG) as a model drug. The crowding effect was achieved by adding polystyrene as a macromolecular co-solute in pre-polymerization mixture. The MIP prepared under the non-MMC condition and the two corresponding non-imprinted particles were tested as controlled vehicles. The release profiles presented zero-order behaviors from two crowding-assisted polymers, the duration of approximately 18h for the crowding-assisted MIP and 10h for the crowding-assisted NIP, respectively while AG were all very rapid released from the other two controlled particles (85% occurring in the first hour). The BET surface area and pore volume of the crowding-assisted MIP were about ten times than those of the controlled MIP. The value of imprinting factor is 6.02 for the crowding-assisted MIP and 1.19 for the controlled MIP evaluated by the equilibrium adsorption experiment. Furthermore, the values of effective diffusivity (Deff) obtained from crowding-assisted MIP (10(-17)cm(2)/s) was about two orders of magnitude smaller than those from the controlled MIP, although the values of free drug diffusivity (D) were all found in the order of 10(-13)cm(2)/s. Compared with the commercial AG tablet, the MMC-assisted MIP gave a markedly high relative bioavailability of 266.3%, whereas the MMC-assisted NIP gave only 57.7%. The results indicated that the MMC condition can modulate the polymer networks approaciate to zero-order release of the drug and maintain the molecular memory pockets, even if under the poor polymerization conditions of MIPs preparation.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Zhao
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Rong-Shan
authors.initials: RS
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jin-Rong
authors.initials: JR
authors.lastname: Yang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China. Electronic address: huangyp100@163.com.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Huang
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Zhao-Sheng
authors.initials: ZS
authors.lastname: Liu
mesh_terms: D000616:Aminoglutethimide / Q000737:chemistry; D000818:Animals; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000295:instrumentation*; D008433:Mathematics; D054802:Molecular Imprinting / Q000379:methods*; D058105:Polymerization; D011137:Polystyrenes / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D003692:Delayed-Action Preparations; D011137:Polystyrenes; D000616:Aminoglutethimide
keywords: Aminoglutethimide; Burst effect; Molecular crowding; Molecularly imprinted polymer; Zero-order release