Thymoquinone (TQ), the main active constituent of Nigella sativa, has demonstrated broad-spectrum antimicrobial, antioxidant, and anti-inflammatory effects, which suggest its potential use in secondary infections caused by COVID-19. However, clinical deployment has been hindered due to its limited aqueous solubility and poor bioavailability. Therefore, a targeted delivery system to the lungs using nanotechnology is needed to overcome limitations encountered with TQ. In this project, a novel TQ-loaded poly(ester amide) based on L-arginine nanoparticles was prepared using the interfacial polycondensation method for a dry powder inhaler targeting delivery of TQ to the lungs. The nanoparticles were characterized by FTIR and NMR to confirm the structure. Transmission electron microscopy and Zetasizer results confirmed the particle diameter of 52 nm. The high-dose formulation showed the entrapment efficiency and loading capacity values of TQ to be 99.77% and 35.56%, respectively. An XRD study proved that TQ did not change its crystallinity, which was further confirmed by the DSC study. Optimized nanoparticles were evaluated for their in vitro aerodynamic performance, which demonstrated an effective delivery of 22.7–23.7% of the nominal dose into the lower parts of the lungs. The high drug-targeting potential and efficiency demonstrates the significant role of the TQ nanoparticles for potential application in COVID-19 and other respiratory conditions.

One of the key challenges in developing a dry powder inhaler (DPI) of an inhalable potent fixed-dose combination (FDC) is the ability of the formulation to generate an effective and reproducible aerosol able to reach the lower parts of the lungs. Herein, a one-step approach is presented to expedite the synthesis of nanoaggregates made from a biocompatible and biodegradable polyamide based on L-lysine amino acid employing market-leading active pharmaceutical ingredients (fluticasone propionate (FP) and salmeterol xinafoate (SAL)) for the management of asthma. The nanoaggregates were synthesized using interfacial polycondensation that produced nanocapsules with an average particle size of 226.7 ± 35.3 nm and zeta potential of −30.6 ± 4.2 mV. Differential scanning calorimetric analysis and x-ray diffraction, as well as scanning electron microscopy of the produced FDC, revealed the ability of the produced nanocapsules to encapsulate the two actives and display the best aerodynamic performance. The FDC nanocapsules displayed 88.5% and 98.5% of the emitted dose for FP and SAL, respectively. The fine particle fraction of the nominated dose was superior to the marketed product (Seretide Diskus®, Brentford, United Kingdom). The in-vitro release study showed an extended drug release profile. Our findings suggest that nanoaggregates using polyamides based on L-lysine and interfacial polycondensation can serve as a good platform for pulmonary drug delivery of FDC systems.

Nanoaggregates made from amino acid-based polymers have been an important platform for targeted drug delivery systems such as the lungs. Therefore, the aim of the present study is to develop tyrosine-based poly(ester amide)s (Tyr-PEA) for dry powder inhaler (DPI) of a potent drug (fluticasone propionate [FP]) using interfacial polymerization. The molecular and surface profiling characteristics were evaluated using Fourier-transformed infrared spectroscopy, X-ray diffraction, transmission electron microscopy, particle size analysis, nuclear magnetic resonance, differential scanning calorimetry, and scanning electron micrographs. The aerodynamic performance was evaluated using the NGI. The results confirmed the formation of the PEA and FP-loaded Tyr-PEA with an average particle size of, 45.39 ± 6.32 nm. The produced FP/Tyr-PEA showed entrapment efficiency and encapsulation capacity of FP of 92.32% and 0.526% respectively, which enabled the delivery of this potent drug in a reasonable dose. The in-vitro performance of the FPloaded PEA was compared to a marketed product and results revealed a significant enhancement of the emitted dose (87.29% vs. 59% respectively [t-test, p < 0.05]). FP-loaded Tyr-PEA produced a higher respirable dose when compared to the marketed FP DPI (48.63 μg vs. 34.15 μg). Overall, FP-loaded Tyr-PEA was successfully prepared with optimal performance. Tyr-PEA-based nanoparticles provide a potential platform for targeted drug delivery, particularly potent actives.