Nanoradioliposomes molecularly modulated to study the lung deep lymphatic drainage.

UNLABELLED: Lung deep lymphatic drainage (LDLD) plays an important role in the removal of foreign materials from lungs being alveolar macrophages the first line of phagocytic defence with high affinity for pathogenic microorganisms. Bacillus subtilis is a well-known genome- decoded saprophyte of the human respiratory tract used in research and in the biotechnology industry. Lung deep lymphatic chains (LDLC) constitute one of the first sites of lung tumours' dissemination. In this work we intended to develop and validate a non-invasive method for assessing LDLC by nanoradioliposomes aerosolised modulated on the Bacillus subtilis spore wall. The final goal was to produce a nanoradioliposome formulation that can mimics the dynamics of preferential removal of spores by LDLD and present the ideal properties as a tracer for molecular imaging studies. Seven different liposomal formulations were tested, and the formulation-F demonstrated physicochemical and radiopharmaceutical properties that make it an ideal candidate as an in vivo probe for molecular imaging studies of the LDLC. Nanoradioliposomes of the formulation-F after labelling with 99mTc-HMPAO were administered as aerosols to 20 Sus scrofa. Hilar and interpulmonary communications were visualized in first 5 minutes post-inhalation, infradiaphragmatic chains between 10 and 20 minutes, the ganglia of the aortic chain at 20 minutes and those of the renal hilar region at 30 minutes. CONCLUSION: the proposed method enables visualization of deep lymphatic lung network and lymph nodes. Besides, this technique involving the modulation of nanoradioliposomes targeting specific organs or tissues may be an important tool for diagnostic or even for therapeutic purposes.

Prenatal administration of vitamin A alters pulmonary and plasma levels of vascular endothelial growth factor in the developing mouse.

Vitamin A and the retinoids play a unique role in mammalian embryonic and foetal development and are essential for both cellular differentiation and the establishment of normal morphogenesis. Vascular endothelial growth factor (VEGF) is a known potent mitogenic factor that plays a key role in lung development and function maintenance. In order to contribute to a better knowledge of the modulating effects of vitamin A in lung development, we investigated the effects of the antenatal administration of vitamin A on VEGF expression in lungs and plasma from foetuses and neonates. Pregnant mice were subjected to subcutaneous administration of vitamin A on the 12th gestational day. The lungs and plasma from foetuses and neonates were collected daily from the 15th gestational day till the day of birth. Our results show that vitamin A modulates VEGF concentrations both in lungs and plasma. Statistically significant differences were observed at gestational days 15 (P = 0.004 for lungs; P < 0.0001 for plasma), 16 (P < 0.0001 for lungs and plasma) and 18 (P < 0.0001 for lungs; P < 0.05 for plasma). Vitamin A tends to increase the expression of this factor in the lung, particularly during the critical period of perinatal adaptation to postnatal life. These effects seem to be spatial and temporally regulated, and point out to the important role of vitamin A during lung development.