Pulmonary Delivery of Nanocomposite Microparticles (NCMPs) incorporating miR-146a for Treatment of COPD

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 m3/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 ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research