The pulmonary direction for drug transport gives more than one benefit over different routes of drug management as a result of its huge surface area, excessive vascularization, and thin blood-alveolar barrier. This method of drug delivery is more convenient for patients, less harmful (non-invasive), and can be used to administer active pharmaceutical ingredients both locally and systemically (APIs). The use of dry powder inhalers (DPI) enables the delivery of APIs to the lung with favorable properties. To do that, the powder should possess critical quality attributes pertinent to size and the ability to reach the lower parts of the respiratory system. Nanocomposite formulations are suitable technology that enables the development of successful DPIs. The methotrexate (MTX) was used as a model to form MTX-Polymer nanocomposites. The MTX-polyamide-disulfide nanocomposites were made by ionic chelation method using different amounts of the independent variable MTX and polymer at two pH levels with varying amounts of ferric chloride (FeCl3) as an across-linker. The loading efficiency and particle size were the dependent variables. These nanocomposites were evaluated using Fourier Transform Infrared (FTIR) and vitro drug release research after they were obtained. The functional groups of the MTX-Polymer nanocomposite were estimated using FTIR. The optimized formula can be collected with the highest loading efficiency (58%) and optimum particle size (120 nm). This formula can be prepared using 0.025 g of drug, 0.0791 g of polymer, 0.05 g of FeCl3, and finally, PH=6.7. The release of MTX from the nanocomposites occurs in two release steps; the first release step started from the beginning up to 60 minutes with maximum release 50%. The second-stage release occurred up to 1400 minutes with complete releases of 80%. The results of this thesis demonstrate that the methotrexate-polymer nanocomposites have a great potential for use as drug delivery systems and pulmonary route.

Methotrexate-Polymer Nanocomposites for Targeted Pulmonary Drug Delivery