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Reference type: Journal
Authors: Tang L, Zhao CY, Wang XH, Li RS, Yang JR, Huang YP, Liu ZS
Article Title: Macromolecular crowding of molecular imprinting: A facile pathway to produce drug delivery devices for zero-order sustained release.
Publication date: 2015
Journal: International Journal of Pharmaceutics
Volume: 496
Issue: (2)
Page numbers: 822-833.
DOI: 10.1016/j.ijpharm.2015.10.031
Alternative URL: http://www.sciencedirect.com/science/article/pii/S0378517315302994

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 18 h for the crowding-assisted MIP and 10 h 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 cm2/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 cm2/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
Template and target information: aminoglutethimide, AG
Author keywords: molecularly imprinted polymer, Molecular crowding, Zero-order release, Burst effect, Aminoglutethimide

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