Novel Thymoquinone Nanoparticles Using Poly(ester amide) Based on L-Arginine-Targeting Pulmonary Drug Delivery

Abstract

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.

Taste Masking of Promethazine Hydrochloride Using l-Arginine Polyamide-Based Nanocapsules

“…However, it should be noted that the polymer exhibited a slight degree of crystallinity as small sharp peaks appeared at around 32° and 45°. Similar results were reported for the slight crystalinity of l -arginine based polymers [ 23 ]. It is clear from Figure 6 c that the superposition of both the drug and polymer peaks was obtained upon physically mixing the polymer and the drug.…”

“…On the other hand, a strong stretching vibration band for the formed amide group C=O was observed at around 1653 cm −1 , and IR bands of the N-H bond appeared at 3160 cm −1 , as shown in Figure 2 b. The results of the l -arginine-based PA are reported in [ 23 ]. A comparison between PMZ/Arg-PA NCs and Arg-PA FTIR spectra shows the same characteristic bands ( Figure 2 b,c).…”

“…The release pattern was fitted using various models according to [ 23 , 54 , 55 ]. The release profile best fits the Higuchi model (see Table 7 , and Figures S3–S7 ).…”

“…IP is built on the reaction of a hydrophilic monomer with a lipophilic monomer at the interface of the two immiscible solvents. Characteristically, in the synthesis of polyamide, the water phase contains the diamine and the organic phase consists of the diacid chloride and an organic solvent [ 23 , 24 ].…”

“…The synthesis of Arg-PA using IP has not been previously reported. Our previous work using arginine-based amino acid poly esteramide was used for the encapsulation of thymoquinone for pulmonary drug delivery [ 23 ]. We also investigated the use of IP to develop polyamides using cystine and tyrosine amino acids [ 24 , 25 ].…”