Macromolecular crowding of molecular imprinting: A facile pathway to produce drug delivery devices for zero-order sustained release

• Published in: International journal of pharmaceutics Vol. 496; no. 2; pp. 822 - 833
• Main Authors: Tang, Lei, Zhao, Chun-Yan, Wang, Xian-Hua, Li, Rong-Shan, Yang, Jin-Rong, Huang, Yan-Ping, Liu, Zhao-Sheng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.12.2015
• Subjects: Aminoglutethimide; Aminoglutethimide - chemistry; Animals; Burst effect; Delayed-Action Preparations; Drug Delivery Systems - instrumentation; Mathematics; Molecular crowding; Molecular Imprinting - methods; Molecularly imprinted polymer; Polymerization; Polystyrenes - chemistry; Rats; Rats, Wistar; Solubility; Zero-order release; Burst effect; Molecular crowding; Aminoglutethimide; Zero-order release; Molecularly imprinted polymer
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2015.10.031

[Display omitted] 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 (10−17cm2/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 10−13cm2/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.