چكيده لاتين
Lung tissue is highly susceptible to disease due to constant exposure to inhaled pathogens, particles, pollutants, and allergens. With the help of two innate and acquired immune systems, airways are protected against infection and inflammation. However, these defense systems are incompletely developed in premature infants. This immaturity in infants leads to respiratory and inflammatory diseases such as bronchopulmonary dysplasia (BPD). According to the progress in the field of treatment of newborns, there is still no definitive treatment that can effectively reduce the symptoms of this disease. Treatment with steroids has been done as a preventive treatment for this disease. Although this method has reduced the disease rate; it has many side effects such as hyperglycemia, high blood pressure, and growth arrest. Based on studies, it has been found that surfactant protein type D present in pulmonary surfactant (SP-D) plays a key role in lung innate immune defense and a protective role against lung infections such as allergies, asthma, and inflammation; Therefore, due to the many properties of these proteins and on the other hand due to the many side effects of using steroids systemically, this approach is created with the help of drug delivery science to design a drug delivery system based on this type of proteins along with steroid drugs inside nanoparticles that can increase the duration of the medicine in the lung. It is obvious that by increasing the shelf life of the drug in the lung environment, the need to extend the dose of the steroid drug is reduced and it reduces the side effects of chemical drugs. In this research, the amniotic fluid of the fetus, which is a source of SP-D, was prepared and the proteins in the liquid that contains the aforementioned protein D are separated after several stages of purification and separation of unwanted particles. Then, with the help of the SDS-PAGE test, the SP-D band was estimated in the target area (below 60 kilodaltons). In the next step, nanoliposomes containing budesonide and proteins containing SP-D were designed by thin layer hydration method and their physicochemical properties were investigated for use in the respiratory system. Based on the results of the Zetasizer device, the average size of nanoparticles was 135.4 nm which was in accordance with the desired size for the particles to reach deep lung areas. The surface charge of nanoparticles was measured with the help of a Zetasizer device in a negative way and in the range of -2.9 mv, which results indicate that it is suitable for respiratory release. According to the drug release studies after 24 hours, the release rate of the drug was 88.57%, which showed that the liposomal form of budesonide maintains the release of the drug for 24 hours or more. As a result, it reduces the need to extend the dose of steroid drugs. Finally, to measure the performance of the system in reducing inflammation in the culture medium, mouse macrophage cell line (RAW264.7) was used for 24 hours and the results indicate a decrease of 25.12% and 19.71% in TNF-α and IL-6 pro-inflammatory factors while using budesonide /proteins containing SP-Dsystem. As a general conclusion, it can be acknowledged that SP-D, due to its anti-inflammatory properties, can be a good candidate to be added to drugs and pulmonary surfactant to control inflammatory diseases.
