RESUMO
Lung cancer is known as the most common cancer. Although the Ramucirumab antibody is a second-line treatment for lung cancer, the high interstitial fluid pressure limits the antibody's performance. In this way, Imatinib is a chemotherapeutic drug to reduce the interstitial fluid pressure. Up to now, unfortunately, both Ramucirumab and imatinib have not been reported in one nanosystem for cancer therapy. To fulfill this shortcoming, this paper aims to design a chitosan nanocarrier that loads imatinib and attaches to Ramucirumab for selective bonding to A549. Therefore, this paper aims to develop a polymeric nanosystem for non-small cell lung cancer (NSCLC) treatment. In first, the chitosan polyethylene glycol nanoparticle is synthesized, loaded with imatinib, and then targeted using Ramucirumab. Afterwards, the CS-PEG-Ab-Im by FTIR, TEM, DLS, zeta potential, and TGA techniques are characterized. The size of CS-PEG-Ab-Im was 25-30 nm, its surface charge was 13.1 mV, and the shape of CS-PEG-Ab-Im was nearly spherical and cylindrical. The therapeutic potential of CS-PEG-Ab-Im was assessed using the A549 cell line. According to the obtained results, the cell viability was 48% after 48 h of treatment of A549 cells using the IC50 concentration of CS-PEG-Ab-Im (100 nanomolar). Moreover, the apoptosis and cell cycle arrest percentages were increased by 3 and 6 times, respectively, as compared to free imatinib. Furthermore, the release rate of imatinib from CS-PEG-Ab-Im in an acidic medium was 17% during 1 h, indicating five times the imatinib release in the natural medium. Eventually, the result of flow cytometry indicates the more apoptotic effect of nanosystem to free imatinib and CS-PEG-Ab. Besides, cell arresting result exhibits the CS-PEG-Ab-Im and causes cell arrested at G1 by %8.17. Thus, it can be concluded that CS-PEG-Ab-Im can be an ideal nanosystem in NSCLC treatment.
Assuntos
Quitosana , Mesilato de Imatinib , Neoplasias Pulmonares , Polietilenoglicóis , Humanos , Mesilato de Imatinib/farmacologia , Quitosana/química , Polietilenoglicóis/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Células A549 , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/química , Portadores de Fármacos/química , Linhagem Celular Tumoral , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismoRESUMO
BACKGROUND: The neonatal mortality rate is a main indicator of the health and development of a country. Having insight into the cause of neonatal deaths may be the first step to reducing it. This paper depicts the cause of newborn deaths in Iran. METHODS: This cross-sectional study was performed on data from the national Iranian Maternal And Neonatal network to investigate all neonatal deaths in the country during the year 2019. The cause of death data were reported according to categories of birth weight, gestational age (GA), death time and place. RESULTS: The main causes of the 9959 neonatal deaths during the study period were respiratory distress syndrome (RDS) (37%), malformation (21%), prematurity of <26 weeks (20%), others (12%), asphyxia (7%) and infection (3%). The major causes of neonatal mortality in delivery rooms were prematurity of <26 weeks and in the inpatient wards the RDS. By increasing the GA and birth weight towards term babies, the rate of RDS gets lower, while that of malformation gets higher. CONCLUSIONS: RDS was the main cause of neonatal mortality in Iran which is seen mainly in preterm babies. Prematurity of <26 weeks was another main cause. Thus, suggestions include reducing prematurity by preconception and pregnancy care and, on the other hand, improving the care of preterm infants in delivery rooms and inpatient wards.