In vivo and in vitro evaluation of pulmonary administration of itraconazole nanostructured lipid carriers for pulmonary aspergillosis.

OBJECTIVE: Pulmonary aspergillosis, which is a secondary complication of fungal pneumonia, is widely considered to have an increasing incidence and high mortality. Itraconazole (Itz) can inhibit ergosterol biosynthesis to treat pulmonary aspergillosis. Nevereless, Itz's clinical application is limited because of its poor water solubility, low oral bioavailability, and systemic hepatotoxicity. In this study, Itz-loaded nanostructured lipid carriers (Itz-NLCs) were developed to improve the in vitro permeability and bioavailability of Itz via pulmonary administration. METHODS: Itz-NLCs were prepared by the emulsification-evaporation method using oleic acid and glycerol monostearate as liquid and solid lipids, respectively. RESULTS: The Itz-NLCs were optimized with tiny particle size, uniform distribution, and excellent entrapment efficiency (EE, 97.57% ± 0.45%). A Xenopus alveolar membrane was used in the permeation study, and the cumulative permeation percentage of Itz was 10% for Itz-NLCs at 8 h, which was 2.50-fold higher than that for Itz suspensions (4%, p < .001). A rabbit pharmacokinetic investigation revealed that Itz-NLCs have an 83.05% absolute bioavailability after intratracheal instillation. CONCLUSIONS: The purpose of Itz-NLCs is to enhance the bioavailability and permeability of Itz in vitro for administration via the lungs.

Deep femoral artery third perforating flap for repair tissue defected of arrounding Pilon fracture in I stage / 中华显微外科杂志

Objective:To investigate the clinical effect of free deep femoral artery third perforating flap repaired soft tissue loss after Pilon fracture surgery in I stage.Methods:Fifteen patients were treated from April, 2013 to January, 2020. Miller AO classification: 8 cases 43-C1, 4 cases 43-C2 and 3 cases 43-C3. All cases were accompanied with severe soft tissue contusion and skin necrosis. After fracture reduction, soft tissue defects, internal fixation exposure and tendon exposure around the wound. Free deep femoral artery third perforating flap (3.5 cm ×15.5 cm to 5.5 cm×12.5 cm) for the repair of soft tissue defects around ankle in the I stage, the blood vessels of the flap were end-to-side anastomosed with vessels of the posterior tibial or anterior tibial. Regular follow-up after surgery.Results:One case of venous crisis occurred, other 14 cases survived, were followed-up from 5 to 18 months, the ankle joint function was good, did not affect the foot shoes, with excellent color and texture, the flap restored protective sensation, and leaving only linear scar, no muscle adhesion.Conclusion:Free deep femoral artery third perforating flap repaired soft tissue loss of surgical incision after fracture operated than significantly reduce the postoperative fracture infection and protect the blood supply around the fracture. It is an effective method of repair.