| Nanocarrier materials play an important role in drug delivery.Solid lipid nanoparticles are a commonly used drug delivery carrier,which has long-term circulation and sustained drug release in vivo,and has good targeting to inflammation,tumors and other parts.Dexamethasone palmitate(Dxp)is the most commonly used drug to treat Acute Lung Injury(ALI),but it has the disadvantages of poor water solubility,short blood half-life and no specific targeting.These problems can be effectively solved by encapsulating dexamethasone palmitate in solid lipid nanoparticles to prepare targeted nano-preparations.Based on the principle of abnormal vascular endothelial cells at the site of pulmonary inflammation and increased vascular permeability,dexamethasone palmitate solid lipid nanoparticles(SLNs-Dxp)were prepared,which can passively target to the site of pulmonary inflammation and slowly release dexamethasone palmitate.The specific idea was that SLNs-Dxp was prepared by film dispersion-ultrasonic method.After single-factor investigation on the preparation process and prescription,the optimal preparation process and prescription was obtained.Then the morphology,particle size,drug embedding rate,and Zeta potential of SLNs-Dxp were characterized.The results showed that the particle size of SLNs-Dxp was 116.8 ± 1.34 nm,the polydispersity index was 0.224 ± 0.003,and the Zeta potential was-42 ± 1.21 m V.The particle size was good,the dispersibility coefficient was less than 0.3,the Zeta potential was greater than-25 m V,and the encapsulation efficiency was 95.7% ± 1.03.Stability studies showed that SLNs-Dxp was stable at 4 ℃ for one week,followed by 25 ℃ and 37 ℃.The in vitro release results showed that the cumulative release rate of SLNs-Dxp within 72 h was less than 10%,indicating that the SLNs-Dxp encapsulated drug was stable and had a long sustained release effect.In addition,the observation under the transmission electron microscope,scanning electron microscope and atomic force microscope showed that the prepared SLNs-Dxp was round and spherical,and no free drug crystals were observed.Then,taking acute lung injury as a disease model,the distribution of SLNs-Di D in vivo was investigated.Fluorescence quantification showed that the fluorescence intensity of SLNs-Di D in LPS-stimulated lung was 3-5 times that of unstimulated lung and 4-6 times that of free Di D.Pharmacodynamic experiments show that SLNs-Dxp administered continuously for 5 times can significantly reduce the edema of acute lung injury compared with once.HE staining showed that SLNs-Dxp could better avoid lung tissue consolidation and reduce inflammatory reaction.The cytotoxicity experiment on human umbilical vein endothelial cells(HUVEC)confirmed that the blank solid lipid nanoparticles had almost no cytotoxicity in the material concentration range of 25 μg/m L-400 μg/m L.The in vivo safety test of the preparation proved that after continuous administration for 7 days,SLNs-Dxp did not cause blood sugar increase after intravenous injection,had little effect on the weight of mice,did not produce anemia in vivo,and did not cause inflammatory reactions in normal lungs and other organs.This study not only provides a theoretical basis for the application of solid lipid nanoparticles in targeted therapy of inflammation,but also provides a new safe and reliable scheme for targeted therapy of acute lung injury. |
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