Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
Int J Pharm. 2019 Oct 5;569:118524. doi: 10.1016/j.ijpharm.2019.118524. Epub 2019 Jul 15.
The treatment and management of COPD by inhalation to the lungs has emerged as an attractive alternative route to oral dosing due to higher concentrations of the drug being administered to site of action. In this study, Nanocomposite Microparticles (NCMPs) of microRNA (miR-146a) containing PGA-co-PDL nanoparticles (NPs) for dry powder inhalation were formulated using l-leucine and mannitol. The spray-drying (Buchi B290) process was optimised and used to incorporate NPs into NCMPs using mix of l-leucine and mannitol excipients in different ratios (F1; 100:0% w/w, F2; 75:25% w/w, F3; 50:50% w/w, F4; 25:75% w/w, F5; 0:100% w/w) to investigate yield %, moisture content, aerosolisation performance and miR-146a biological activity. The optimum condition was performed at feed rate 0.5 ml/min, aspirator rate 28 m/h, atomizing air flow rate 480 L/h, and inlet drying temperature 70 °C which produced highest yield percentage and closest recovered NPs size to original prior spray-drying. The optimum formulation (F4) had a high yield (86.0 ± 15.01%), recovered NPs size after spray-drying 409.7 ± 10.05 nm (initial NPs size 244.8 ± 4.40 nm) and low moisture content (2.02 ± 0.03%). The aerosolisation performance showed high Fine Particle Fraction (FPF) 51.33 ± 2.9%, Emitted Dose (ED) of 81.81 ± 3.0%, and the mass median aerodynamic diameter (MMAD) was ≤5 µm suggesting a deposition in the respirable region of the lungs. The biological activity of miR-146a was preserved after spray-drying process and miR-146a loaded NCMPs produced target genes IRAK1 and TRAF6 silencing. These results indicate the optimal process parameters for the preparation of NCMPs of miR-146a-containing PGA-co-PDL NPs suitable for inhalation in the treatment and management of COPD.
采用吸入肺部的方式治疗和管理 COPD 已成为一种有吸引力的替代口服给药途径，因为与口服给药相比，肺部能够输送更高浓度的药物。在这项研究中，采用左旋亮氨酸和甘露醇制备了载有 miR-146a 的 PGA-co-PDL 纳米颗粒（NPs）的纳米复合微粒（NCMPs）干粉吸入剂。通过喷雾干燥（Buchi B290）工艺对其进行了优化，并使用左旋亮氨酸和甘露醇赋形剂以不同比例（F1；100：0%w/w、F2；75：25%w/w、F3；50：50%w/w、F4；25：75%w/w、F5；0：100%w/w）将 NPs 合并到 NCMPs 中，以研究收率、水分含量、雾化性能和 miR-146a 的生物学活性。优化条件为进料速度 0.5ml/min、吸气速度 28m/h、雾化空气流速 480L/h、进口干燥温度 70°C，在此条件下，收率最高，且喷雾干燥后回收的 NPs 粒径最接近原始 NPs（喷雾干燥前为 409.7±10.05nm，原始 NPs 粒径为 244.8±4.40nm），水分含量最低（2.02±0.03%）。雾化性能显示出高的细颗粒分数（FPF）51.33±2.9%、发射剂量（ED）81.81±3.0%和质量中值空气动力学直径（MMAD）≤5μm，提示药物在肺部可呼吸区域沉积。miR-146a 经喷雾干燥后仍保持生物活性，负载 miR-146a 的 NCMPs 能使 IRAK1 和 TRAF6 靶基因沉默。这些结果表明，优化后的参数可用于制备适合治疗和管理 COPD 的载 miR-146a PGA-co-PDL NPs 的 NCMPs。
