Ribeiro Lígia N M, Rodrigues da Silva Gustavo H, Couto Verônica M, Castro Simone R, Breitkreitz Márcia C, Martinez Carolina S, Igartúa Daniela E, Prieto Maria J, de Paula Eneida
Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.
Department of Analytical Chemistry, Institute of Chemistry, University of Campinas, Campinas, Brazil.
Front Chem. 2020 Nov 12;8:589503. doi: 10.3389/fchem.2020.589503. eCollection 2020.
In recent years, advanced nanohybrid materials processed as pharmaceuticals have proved to be very advantageous. Triptans, such as the commercially available intranasal sumatriptan (SMT), are drugs employed in the treatment of painful migraine symptoms. However, SMT effectiveness by the intranasal route is limited by its high hydrophilicity and poor mucoadhesion. Therefore, we designed hybrid nanoemulsions (NE) composed of copaiba oil as the organic component plus biopolymers (xanthan, pectin, alginate) solubilized in the continuous aqueous phase, aiming at the intranasal release of SMT (2% w/v). Firstly, drug-biopolymer complexes were optimized in order to decrease the hydrophilicity of SMT. The resultant complexes were further encapsulated in copaiba oil-based nanoparticles, forming NE formulations. Characterization by FTIR-ATR, DSC, and TEM techniques exposed details of the molecular arrangement of the hybrid systems. Long-term stability of the hybrid NE at 25°C was confirmed over a year, regarding size (~ 120 nm), polydispersity (~ 0.2), zeta potential (~ -25 mV), and nanoparticle concentration (~ 2.10 particles/mL). SMT encapsulation efficiency in the formulations ranged between 41-69%, extending the release time of SMT from 5 h (free drug) to more than 24 h. The alginate-based NE was selected as the most desirable system and its nanotoxicity was evaluated in a zebrafish model. Hybrid NE treatment did not affect spontaneous movement or induce morphological changes in zebrafish larvae, and there was no evidence of mortality or cardiotoxicity after 48 h of treatment. With these results, we propose alginate-based nanoemulsions as a potential treatment for migraine pain.
近年来，作为药物加工的先进纳米杂化材料已被证明具有很大优势。曲坦类药物，如市售的鼻内舒马曲坦（SMT），是用于治疗偏头痛疼痛症状的药物。然而，SMT通过鼻内途径的有效性受到其高亲水性和差的粘膜粘附性的限制。因此，我们设计了由巴西香脂油作为有机成分加溶解在连续水相中的生物聚合物（黄原胶、果胶、藻酸盐）组成的混合纳米乳液（NE），旨在实现SMT（2% w/v）的鼻内释放。首先，对药物 - 生物聚合物复合物进行优化以降低SMT的亲水性。所得复合物进一步封装在基于巴西香脂油的纳米颗粒中，形成NE制剂。通过FTIR - ATR、DSC和TEM技术进行的表征揭示了杂化系统分子排列的细节。在25°C下，混合NE的长期稳定性在一年多的时间里得到证实，涉及粒径（约120 nm）、多分散性（约0.2）、zeta电位（约 - 25 mV）和纳米颗粒浓度（约2.10颗粒/mL）。制剂中SMT的包封效率在41 - 69%之间，将SMT的释放时间从5小时（游离药物）延长至超过24小时。基于藻酸盐的NE被选为最理想的系统，并在斑马鱼模型中评估了其纳米毒性。混合NE处理不影响斑马鱼幼虫的自发运动或诱导形态变化，并且在处理48小时后没有死亡或心脏毒性的证据。基于这些结果，我们提出基于藻酸盐的纳米乳液作为偏头痛疼痛的潜在治疗方法。
