Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM-ENSCM, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.
Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM-ENSCM, Place Eugène Bataillon, 34095 Montpellier Cedex 5, France.
Int J Pharm. 2017 Nov 5;532(2):790-801. doi: 10.1016/j.ijpharm.2017.07.074. Epub 2017 Jul 27.
Combined therapy is a global strategy developed to prevent drug resistance in cancer and infectious diseases. In this field, there is a need of multifunctional drug delivery systems able to co-encapsulate small drug molecules, peptides, proteins, associated to targeting functions, nanoparticles. Silylated hydrogels are alkoxysilane hybrid polymers that can be engaged in a sol-gel process, providing chemical cross linking in physiological conditions, and functionalized biocompatible hybrid materials. In the present work, microgels were prepared with silylated (hydroxypropyl)methyl cellulose (Si-HPMC) that was chemically cross linked in soft conditions of pH and temperature. They were prepared by an emulsion templating process, water in oil (W/O), as microreactors where the condensation reaction took place. The ability to functionalize the microgels, so-called FMGs, in a one-pot process, was evaluated by grafting a silylated hydrophilic model drug, fluorescein (Si-Fluor), using the same reaction of condensation. Biphasic microgels (BPMGs) were prepared to evaluate their potential to encapsulate lipophilic model drug (Nile red). They were composed of two separate compartments, one oily phase (sesame oil) trapped in the cross linked Si-HPMC hydrophilic phase. The FMGs and BPMGs were characterized by different microscopic techniques (optic, epi-fluorescence, Confocal Laser Scanning Microscopy and scanning electronic microscopy), the mechanical properties were monitored using nano indentation by Atomic Force Microscopy (AFM), and different preliminary tests were performed to evaluate their chemical and physical stability. Finally, it was demonstrated that it is possible to co-encapsulate both hydrophilic and hydrophobic drugs, in silylated microgels, that were physically and chemically stable. They were obtained by chemical cross linking in soft conditions, and without surfactant addition during the emulsification process. The amount of drug loaded was in favor of further biological activity. Mechanical stimulations should be necessary to trigger drug release.
联合疗法是一种为防止癌症和传染病产生抗药性而开发的全球策略。在该领域，需要多功能药物输送系统，能够共同封装小分子药物、肽、蛋白质，并与靶向功能相结合，还需要纳米颗粒。硅烷化水凝胶是烷氧基硅烷杂化聚合物，可以参与溶胶-凝胶过程，在生理条件下提供化学交联，并提供功能化的生物相容性杂化材料。在本工作中，通过乳液模板法（W/O），使用相同的缩合反应，在温和的 pH 和温度条件下将硅烷化（羟丙基）甲基纤维素（Si-HPMC）化学交联制备微凝胶。通过一锅法评估了微凝胶（FMG）的功能化能力，即用硅烷化的亲水性模型药物荧光素（Si-Fluor）进行接枝，使用相同的缩合反应。为了评估它们封装亲脂性模型药物（Nile red）的潜力，制备了双相微凝胶（BPMGs）。它们由两个独立的隔室组成，一个是油性相（芝麻油）被困在交联的 Si-HPMC 亲水相中。通过不同的显微镜技术（光学、荧光、共聚焦激光扫描显微镜和扫描电子显微镜）对 FMG 和 BPMG 进行了表征，通过原子力显微镜（AFM）的纳米压痕监测了机械性能，并进行了不同的初步测试以评估其化学和物理稳定性。最后，证明了在物理和化学上稳定的硅烷化微凝胶中，可以共同封装亲水性和疏水性药物。这些微凝胶是通过在温和条件下化学交联得到的，并且在乳化过程中没有添加表面活性剂。负载的药物量有利于进一步的生物活性。机械刺激可能是触发药物释放所必需的。
