Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, PR China; Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029 China.
Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, PR China; Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029 China.
Colloids Surf B Biointerfaces. 2020 May;189:110844. doi: 10.1016/j.colsurfb.2020.110844. Epub 2020 Feb 4.
Drug distribution in polymer dissolvable microneedles (MNs) is essential for enhancing the efficiency of drug delivery. In the present work, multiscale simulation was applied to study the interactions between polymer and drug molecules, which may influence the drug distribution in the MNs. In this study, Hyaluronic acid (HA) and Polyvinyl alcohol (PVA) were used to fabricate the MNs and sulfonhodamine B (SRB) was selected as the model drug. Firstly, from the quantum chemical calculations, the global electronegativity of HA (3.786 eV) is stronger than that of PVA (2.435 eV), which means that HA owns stronger electronegativity. The Flory-Huggins parameter of HA-SRB is -1.16 which is lower than that of PVA-SRB (53.51), indicating that HA has better compatibility with SRB molecules than PVA. From molecular dynamic simulations, the binding energy of HA-SRB is 93.52 kcal/mol which is much higher than that of PVA-SRB (-2.40 kcal/mol), meaning that HA is easier than PVA to combined with SRB. The mesoscale-based dissipative particle dynamics (DPD) simulations were applied to visualize the diffusion behavior of SRB and the swelling properties of the polymers. All the results indicated that SRB has a lower diffusion coefficient in PVA solution than that in HA solution, which may prevent the diffusion of drug from MN tips to the bases, facilitating the fabrication of MNs with drug concentrated MN tips. Finally, the SRB loaded PVA and HA MNs were prepared and the experimental results are consisted with the simulation results.
药物在聚合物可溶解微针（MNs）中的分布对于提高药物输送效率至关重要。在本工作中，应用多尺度模拟研究了聚合物和药物分子之间的相互作用，这些相互作用可能会影响药物在 MNs 中的分布。在这项研究中，使用透明质酸（HA）和聚乙烯醇（PVA）来制备 MNs，并选择磺基罗丹明 B（SRB）作为模型药物。首先，通过量子化学计算，HA 的全局电负性（3.786 eV）强于 PVA 的全局电负性（2.435 eV），这意味着 HA 具有更强的电负性。HA-SRB 的 Flory-Huggins 参数为-1.16，低于 PVA-SRB（53.51），表明 HA 与 SRB 分子的相容性优于 PVA。从分子动力学模拟来看，HA-SRB 的结合能为 93.52 kcal/mol，远高于 PVA-SRB（-2.40 kcal/mol），这意味着 HA 比 PVA 更容易与 SRB 结合。基于介观的耗散粒子动力学（DPD）模拟用于可视化 SRB 的扩散行为和聚合物的溶胀特性。所有结果均表明，SRB 在 PVA 溶液中的扩散系数低于在 HA 溶液中的扩散系数，这可能会阻止药物从 MN 尖端向底部扩散，有利于制备药物集中在 MN 尖端的 MNs。最后，制备了负载 SRB 的 PVA 和 HA MNs，实验结果与模拟结果一致。
