Zhou Jiayi, Horev Benjamin, Hwang Geelsu, Klein Marlise I, Koo Hyun, Benoit Danielle S W
Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA.
Biofilm Research Lab, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
J Mater Chem B. 2016 May 14;4(18):3075-3085. doi: 10.1039/C5TB02054A. Epub 2015 Nov 20.
We previously reported on cationic, pH-responsive p(DMAEMA)--p(DMAEMA-co-BMA-co-PAA) block copolymer micelles with high affinity for dental and biofilm surfaces and efficient anti-bacterial drug release in response to acidic pH, characteristic of cariogenic (tooth-decay causing) biofilm microenvironments. Here, we show that micelle pH-responsive behaviors can be enhanced through alterations in corona:core molecular weight ratios (CCR). Although similarly stable at physiological pH, upon exposure to acidic pH, micelles with CCR of 4.1 were less stable than other CCR examined. Specifically, a 1.5-fold increase in critical micelle concentration (CMC) and ~50% decrease in micelle diameters were observed for micelles with CCR of 4.1, compared to no changes in micelles with CCR of 0.8. While high CCR was shown to enhance pH-responsive drug release, it did not alter drug loading and dental surface binding of micelles. Diblocks were shown to encapsulate the antibacterial drug, farnesol, at maximal loading capacities of up to ~27 wt% and at >94% efficiencies, independent of CCR or core size, resulting in micelle diameter increases due to contributions of drug volume. Additionally, micelles with small diameters (17 nm) show high binding capacity to hydroxyapatite and dental pellicle emulating surfaces based on Langmuir fit analyses of binding data. Finally, micelles with high CCR that have enhanced pH-responsive drug release and binding were shown to exhibit greater antibiofilm efficacy in situ. Overall, these data demonstrate how factors essential for nanoparticle carrier (NPC)-mediated drug deliverycan be enhanced modification of diblock characteristics, resulting in greater antibiofilm efficacy .
我们之前报道了阳离子型、pH响应性的p(DMAEMA)--p(DMAEMA-co-BMA-co-PAA)嵌段共聚物胶束，其对牙齿和生物膜表面具有高亲和力，并能在酸性pH下有效释放抗菌药物，这是致龋（导致蛀牙）生物膜微环境的特征。在此，我们表明可以通过改变冠层：核层分子量比（CCR）来增强胶束的pH响应行为。尽管在生理pH下同样稳定，但在暴露于酸性pH时，CCR为4.1的胶束比其他检测的CCR更不稳定。具体而言，与CCR为0.8的胶束无变化相比，CCR为4.1的胶束的临界胶束浓度（CMC）增加了约1.5倍，胶束直径减小了约50%。虽然高CCR被证明能增强pH响应性药物释放，但它并未改变胶束的药物负载和牙齿表面结合。二嵌段被证明能以高达约27 wt%的最大负载容量和>94%的效率包封抗菌药物法尼醇，这与CCR或核尺寸无关，由于药物体积的贡献导致胶束直径增加。此外，基于结合数据的朗缪尔拟合分析，小直径（约17 nm）的胶束对羟基磷灰石和模拟牙齿薄膜的表面具有高结合能力。最后，具有增强的pH响应性药物释放和结合能力的高CCR胶束在原位显示出更大的抗生物膜功效。总体而言，这些数据证明了如何通过修饰二嵌段特性来增强纳米颗粒载体（NPC）介导的药物递送所需的因素，从而产生更大的抗生物膜功效。
