School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China.
Medical Center, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, Shandong, People's Republic of China.
Drug Deliv Transl Res. 2020 Oct;10(5):1520-1530. doi: 10.1007/s13346-020-00735-2.
In order to improve the bioavailability of curcumin (Cur) and patient compliance, a type of novel hyaluronic acid (HA) composite microneedles containing Cur-loaded micelles was designed in this paper. On the one hand, the microneedles matrix solution was prepared by screening the optimal concentration of HA and the better proportion of HA to sodium carboxymethyl starch (CMS-Na). On the other hand, the amphiphilic polymer, named as Quercetin-Dithiodipropionic Acid-Oligomeric Hyaluronic Acid (Que-DA-oHA), was synthesized and characterized using H-NMR. Subsequently, the dialysis method was used to prepare Cur-loaded Que-DA-oHA micelles with an average size of 172.6 ± 11.4 nm and zeta potential of - 33.71 ± 0.45 mV. A micromolding process was used to prepare the micelle-loaded HA composite microneedles. It had been found that when the concentration of HA was 200 mg/mL and the mass ratio of HA to CMS-Na was 2:1, the prepared HA composite microneedles had good mechanical strength. In-skin dissolution kinetics showed that the micelle-loaded HA composite microneedles could dissolve quickly in the skin. In vitro permeation study indicated that the microneedles delivered 74.7% of their drug load over 6 h, which exhibited remarkable drug permeation properties in a short time. Here, we creatively combined micellar technology with microneedle technology to rapidly deliver Cur transdermally for diseases treatment such as melanoma. Graphical abstract.
为了提高姜黄素（Cur）的生物利用度和患者顺应性，本文设计了一种新型的含载姜黄素胶束的透明质酸（HA）复合微针。一方面，通过筛选最佳 HA 浓度和更好的 HA 与羧甲基淀粉钠（CMS-Na）的比例来制备微针基质溶液。另一方面，合成了一种两亲性聚合物，命名为槲皮素-二硫代二丙酸-寡聚透明质酸（Que-DA-oHA），并通过 1H-NMR 进行了表征。随后，采用透析法制备了平均粒径为 172.6±11.4nm、zeta 电位为-33.71±0.45mV 的载姜黄素的 Que-DA-oHA 胶束。采用微模塑工艺制备载药胶束的 HA 复合微针。结果发现，当 HA 浓度为 200mg/mL，HA 与 CMS-Na 的质量比为 2:1 时，所制备的 HA 复合微针具有良好的机械强度。在皮内溶解动力学研究中发现，载药 HA 复合微针在皮肤中能迅速溶解。体外渗透研究表明，微针在 6h 内输送了 74.7%的药物载量，在短时间内表现出显著的药物渗透性能。在这里，我们创造性地将胶束技术与微针技术相结合，快速透皮递药治疗黑色素瘤等疾病。
