Çeşitli Hastalıkların Tedavisinde Kullanılan İlaçların ve İlaç Yüklü Taşıyıcıların Alveoller ve Akciğer Yüzey Aktif Maddesi İle Olası Etkileşiminin İncelenmesi

Abstract

Surfactants contains hydrophobic tail and hydrophilic head groups and they cause surface tension to decrease by being adsorbed on the liquid-air interface. Surfactants found naturally in the human body are found in the lungs. Lungs are preferred as the drug delivery route because they are in constant contact with air and have large surface areas. Drug transport from the lungs is a non-invasive method that can be used not only in the treatment of lung diseases, but also in the treatment of other diseases. After drugs reach the alveoli, they interact with the pulmonary surfactant found on the alveoli by pulmonary. It is important that both drug activity and pulmonary surfactant function are not impaired. Ciprofloxacin (antibiotic), Naproxen (antiinflammatory) and dipyridamole (cardiac) have been used as model medicines for different diseases in this study. To investigate the interaction of these drugs, dipalmitolphosphatidylcholine (DPPC), the most abundant phospholipid in the lung surfactant, and bovine natural surfactant (BNS) from bovine lung lavage were used as model surfactant. Interfacial properties, dynamic adsorption properties and interactions with each other were investigated by using different ratios with model surfactants and drugs. Interfacial properties were investigated with LB trough and fluorescence microscopy (FM). The LB trough results show that the effects of the drugs on the surface pressure-area isotherms of the monolayers are not so big and they do not change the elasticity values. The FM images show that it is seen that the monolayer reduces LC domains and fluidizes the surfactant monolayer. In addition to giving medicines in solution, it can also be delivered using a carrier. There are many particles in the literature used as drug carriers. However, nano-sized particles are preferred because the particle size is important when the drug is administered from the lungs. In order to reduce the toxic properties of the used particles, biocompatible lipid-based nanoparticles are preferred. In this study, lipid-based biocompatible and high-stability solid lipid nanoparticles (KLN) were synthesized and used. Interactions with surfactants have been investigated when KLNs used as drug carriers reach the lungs. Analysis of the interface properties of the KLNs was performed by pendant drop as well as the LB trough method. Using the highest amount of KLN worked, 0.1 Hz frequency oscillation was performed and THD (total harmonic distortion) was calculated and the effect of particles on the rheological properties of the monolayer was investigated. The addition of KLNs to the monolayer did not seem to distort the linearity much. In addition, as interactions with drug loaded KLN are important, Naproxen was chosen primarily because antiinflammatory drugs as model drugs have been used for cancer treatment in recent years. Naproxen loaded KLNs were obtained, resulting in the characterization that the resulting free KLN did not change its physical properties. Then Naproxen release studies were carried out from Naproxen loaded KLN. The Naproxen encapsulation efficiency of the KLNs was calculated as 95%. It released about 15% of Naproxen in 250 minutes, then continued to release at a decreasing rate and attacked about 25% in 24 hours. The simultaneous addition of Naproxen and KLN in the presence of a surfactant monolayer showed similar results with the addition of KLN alone, but the result of the presence of Naproxen did not appear to be as much as observed with KLN alone. This is due to the fact that Naproxen is negatively charged in ambient conditions and interacts with negatively charged KLN. In summary, the suitability of drug delivery from the lungs in the treatment of various diseases and the suitability of lipid-based KLNs for their use as carrier systems have been shown.