Dynamically Crosslinked Hydrogels

说明书(申请人提供)：提出了一种对三磷酸腺苷(ATP)有反应的动态交联水凝胶。这种水凝胶将由HPMA[N-(2-羟丙基)甲基丙烯酰胺]共聚物和微管细丝组成的互穿网络组成。相互穿透网络将通过依赖于ATP的运动在马达蛋白中进行主动交联。据预测，这种水凝胶在有三磷酸腺苷存在的情况下会迅速而有力地收缩，就像合成肌肉一样。该提案的具体目标是：i.)通过用HPMA聚合物刷修饰微管来稳定微管在整个PHPMA基质中的分散，ii.)通过将重组动蛋白马达通过其货物结合端与PHPMA偶联来使微管和PHPMA基质交联。用活性激动素进行交联的水凝胶的物理性质将与凝胶组成和交联度有关。以表征水凝胶的ATP响应性。将确定药物(阿霉素)对三磷酸腺苷的反应的卸载率和程度。这些新型水凝胶可能在药物输送方面有广泛的生物医学应用，作为医疗设备中的活性表面涂层或微执行器。

DESCRIPTION (provided by applicant): Dynamically crosslinked hydrogels that respond to adenosine triphosphate (ATP) are proposed. The hydrogels will consist of interpenetrating networks of HPMA [N-(2-hydroxypropyl)methacrylamide] copolymers and microtubule filaments. The interpenetrating networks will be actively crosslinked through ATP-dependent kinesin motor proteins. The hydrogels are predicted to contract rapidly and forcefully in the presence of ATP, like a synthetic muscle. The specific aims of the proposal are: i.) To stabilize the dispersion of microtubules throughout a pHPMA matrix by modifying microtubules with HPMA polymer brushes, ii.) To crosslink microtubules and a pHPMA matrix by conjugating recombinant kinesin motors through their cargo-binding end to pHPMA. The physical properties of hydrogels crosslinked with active kinesin will be characterized in relation to the gel composition and crosslinking density, iii.) To characterize the ATP responsiveness of the hydrogels. The rate and extent of unloading of a drug (doxorubicin) in response to ATP will be determined. These novel hydrogels may find wide ranging biomedical applications in drug delivery, as active surface coatings or microactuators in medical devices.