Pimenta Barbara V, Madrid Rafael R M, Mathews Patrick D, Riske Karin A, Loh Watson, Angelov Borislav, Angelova Angelina, Mertins Omar
Laboratory of Nano Bio Materials (LNBM), Department of Biophysics, Paulista Medical School, Federal University of Sao Paulo (UNIFESP), 04023-062 Sao Paulo, Brazil.
Institute of Chemistry, State University of Campinas (UNICAMP), 13083-970 Campinas, Brazil.
J Mater Chem B. 2023 Mar 15;11(11):2490-2503. doi: 10.1039/d2tb02670h.
Nano-structured and functionalized materials for encapsulation, transport, targeting and controlled release of drugs are of high interest to overcome low bioavailability in oral administration. We develop lipid-based cubosomes, which are surface-functionalized with biocompatible chitosan--arginine and alginate, displaying internal liquid crystalline structures. Polyelectrolyte-shell (PS) cubosomes have pH-responsive characteristics profitable for oral delivery. The obtained PScubosomes can strongly interact with serum albumin, a protein which is released in the stomach under gastric cancer conditions. An effective thermodynamic PScubosome-protein interaction was characterized at pH 2.0 and 7.4 by isothermal titration calorimetry at 37 °C. A high increment of the albumin conformation transition temperature was evidenced by differential scanning calorimetry upon incubation with PScubosomes. The performed structural studies by synchrotron small-angle X-ray scattering (SAXS) revealed essential alterations in the internal liquid crystalline topology of the nanocarriers including an 3 to 3 transition and a reduction of the cubic lattice parameters. The PScubosome nanoparticle interaction with serum albumin, leading to inner structural changes in a range of temperatures, promoted the release of water from the cubosomal nanochannels. Altogether, the results revealed effective interactions of the PScubosomes with albumin under simulated gastrointestinal pH conditions and suggested promising nanocarrier characteristics for triggered oral drug release.
用于药物包封、运输、靶向和控释的纳米结构及功能化材料，对于克服口服给药时的低生物利用度具有重要意义。我们开发了基于脂质的立方液晶纳米粒，其表面用生物相容性壳聚糖-精氨酸和海藻酸盐进行功能化修饰，呈现出内部液晶结构。聚电解质壳（PS）立方液晶纳米粒具有pH响应特性，有利于口服给药。所制备的PS立方液晶纳米粒能与血清白蛋白强烈相互作用，血清白蛋白是一种在胃癌条件下于胃中释放的蛋白质。在37℃下，通过等温滴定量热法在pH 2.0和7.4条件下对PS立方液晶纳米粒与蛋白质之间有效的热力学相互作用进行了表征。差示扫描量热法表明，与PS立方液晶纳米粒孵育后，白蛋白构象转变温度有显著升高。同步加速器小角X射线散射（SAXS）进行的结构研究揭示了纳米载体内部液晶拓扑结构的重要变化，包括从一种立方相到另一种立方相的转变以及立方晶格参数的减小。PS立方液晶纳米粒与血清白蛋白的相互作用导致其在一定温度范围内内部结构发生变化，促进了立方液晶纳米通道中水的释放。总之，这些结果揭示了在模拟胃肠道pH条件下PS立方液晶纳米粒与白蛋白之间的有效相互作用，并表明其具有触发口服药物释放的良好纳米载体特性。
