Dolci Luisa Stella, Perone Rosaria Carmela, Di Gesù Roberto, Kurakula Mallesh, Gualandi Chiara, Zironi Elisa, Gazzotti Teresa, Tondo Maria Teresa, Pagliuca Giampiero, Gostynska Natalia, Baldassarro Vito Antonio, Cescatti Maura, Giardino Luciana, Focarete Maria Letizia, Calzà Laura, Passerini Nadia, Bolognesi Maria Laura
Department of Pharmacy and BioTechnology, Alma Mater Studiorum-University of Bologna, Via S. Donato 15, 40127 Bologna, BO, Italy.
Interdepartmental Center for Health Sciences & Technologies (HST), CIRI-SDV, Alma Mater Studiorum-University of Bologna, Via Tolara di Sopra 41/E, 40064 Ozzano Emilia, BO, Italy.
Pharmaceutics. 2021 Jun 8;13(6):848. doi: 10.3390/pharmaceutics13060848.
Vascular and traumatic injuries of the central nervous system are recognized as global health priorities. A polypharmacology approach that is able to simultaneously target several injury factors by the combination of agents having synergistic effects appears to be promising. Herein, we designed a polymeric delivery system loaded with two drugs, ibuprofen (Ibu) and thyroid hormone triiodothyronine (T3) to in vitro release the suitable amount of the anti-inflammation and the remyelination drug. As a production method, electrospinning technology was used. First, Ibu-loaded micro (diameter circa 0.95-1.20 µm) and nano (diameter circa 0.70 µm) fibers were produced using poly(l-lactide) PLLA and PLGA with different lactide/glycolide ratios (50:50, 75:25, and 85:15) to select the most suitable polymer and fiber diameter. Based on the in vitro release results and in-house knowledge, PLLA nanofibers (mean diameter = 580 ± 120 nm) loaded with both Ibu and T3 were then successfully produced by a co-axial electrospinning technique. The in vitro release studies demonstrated that the final Ibu/T3 PLLA system extended the release of both drugs for 14 days, providing the target sustained release. Finally, studies in cell cultures (RAW macrophages and neural stem cell-derived oligodendrocyte precursor cells-OPCs) demonstrated the anti-inflammatory and promyelinating efficacy of the dual drug-loaded delivery platform.
中枢神经系统的血管和创伤性损伤被视为全球卫生重点。一种能够通过具有协同作用的药物组合同时针对多种损伤因素的多药理学方法似乎很有前景。在此，我们设计了一种负载两种药物（布洛芬（Ibu）和甲状腺激素三碘甲状腺原氨酸（T3））的聚合物递送系统，以在体外释放适量的抗炎和髓鞘再生药物。作为一种生产方法，使用了静电纺丝技术。首先，使用具有不同丙交酯/乙交酯比例（50:50、75:25和85:15）的聚（L-丙交酯）PLLA和PLGA制备负载Ibu的微纤维（直径约0.95-1.20 µm）和纳米纤维（直径约0.70 µm），以选择最合适的聚合物和纤维直径。基于体外释放结果和内部知识，然后通过同轴静电纺丝技术成功制备了同时负载Ibu和T3的PLLA纳米纤维（平均直径 = 580 ± 120 nm）。体外释放研究表明，最终的Ibu/T3 PLLA系统将两种药物的释放延长了14天，实现了目标缓释。最后，细胞培养研究（RAW巨噬细胞和神经干细胞衍生的少突胶质细胞前体细胞-OPCs）证明了双载药递送平台的抗炎和促髓鞘形成功效。
