已使用专门为牛奶/食品混合物应用设计的喷雾干燥程序成功合成了由Levan和Dolutegravir(DTG)组成的纳米颗粒。Levan,从枯草芽孢杆菌微生物中获得,使用MALDI-TOF和固态NMR技术彻底表征以确认其性质。在本研究中,这种分离的Levan被用作药物递送应用的载体。优化的喷雾干燥纳米颗粒表现出光滑的表面形态,粒径范围为195至329nm。在水介质中进行的体外药物释放实验中,喷雾干燥的纳米粒子显示出100%的释放,而未加工的药物在24小时结束时仅表现出50%的释放。值得注意的是,牛奶中的药物释放量与普通介质中的药物释放量相当,说明兼容性。观察到的纳米颗粒的改善的溶解速率可归因于DTG从其结晶状态到无定形状态的固态转化(通过XRD分析证实)。使用傅里叶变换红外光谱和热重-差示扫描量热分析验证药物的稳定性。为了评估体外细胞毒性,3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴化物(MTT)测定,这表明未加工DTG的CC50值为88.88±5.10µg/mL,DTG纳米颗粒的CC50值为101.08±37.37µg/mL。这些结果表明纳米颗粒的毒性与未加工的药物相当。此外,发现纳米粒子在人类细胞系中的抗HIV活性与纯药物相似,强调DTG在对抗HIV中的治疗功效。
Nanoparticles composed of
Levan and Dolutegravir (DTG) have been successfully synthesized using a spray drying procedure specifically designed for milk/food admixture applications.
Levan, obtained from the microorganism Bacillus subtilis, was thoroughly characterized using MALDI-TOF and solid-state NMR technique to confirm its properties. In the present study, this isolated
Levan was utilized as a carrier for drug delivery applications. The optimized spray-dried nanoparticles exhibited a smooth surface morphology with particle sizes ranging from 195 to 329 nm. In the in-vitro drug release experiments conducted in water media, the spray-dried nanoparticles showed 100 % release, whereas the unprocessed drug exhibited only 50 % release at the end of 24 h. Notably, the drug release in milk was comparable to that in plain media, indicating the compatibility. The improved dissolution rate observed for the nanoparticles could be attributed to the solid-state conversion (confirmed by XRD analysis) of DTG from its crystalline to amorphous state. The stability of the drug was verified using Fourier Transform Infra-Red Spectroscopy and Thermogravimetry-Differential Scanning Calorimetry analysis. To evaluate the in-vitro cellular toxicity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted, which revealed the CC50 value of 88.88 ± 5.10 µg/mL for unprocessed DTG and 101.08 ± 37.37 µg/mL for DTG nanoparticles. These results indicated that the toxicity of the nanoparticles was comparable to the unprocessed drug. Furthermore, the anti-HIV activity of the nanoparticles in human cell lines was found to be similar to that of the pure drug, emphasizing the therapeutic efficacy of DTG in combating HIV.