Development and Evaluation of Aloperine-Loaded Nanostructured Lipid Carriers for the Treatment of Pulmonary Arterial Hypertension

Hui Liu,1,* Siyun Liu,1,* Pengsheng Ma,1 Long Ma,1 Yuxin Liu,1 Fang Zhao,2 Ru Zhou1,3,4 1School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 3NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 4Ningxia Characteristic Traditional Chinese Medicine Modernization Engineering Technology Research Center, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ru Zhou, School of Pharmacy, Ningxia Medical University, Xingqing, Ningxia, Yinchuan, 750004, People’s Republic of China, Email [email protected] Fang Zhao, General Hospital of Ningxia Medical University, Xingqing, Ningxia, Yinchuan, 750004, People’s Republic of China, Email [email protected]: This study focuses on the development and evaluation of nanostructured lipid carriers (NLCs) loaded with aloperine as a potential therapeutic approach for the treatment of pulmonary arterial hypertension.Methods: The NLCs were designed to enhance the solubility, stability, and bioavailability of aloperine, a compound with vasodilatory and anti-inflammatory properties. Through a series of experiments including single-factor experimentation, transmission electron microscopy, high-performance liquid chromatography, in vivo pharmacokinetics, and tissue distribution studies, we assessed the physicochemical properties, drug release profiles, and in vitro and in vivo performance of this novel nanocarrier.Results: The prepared aloperine-loaded NLCs exhibited a milky white and translucent suspension appearance, presenting a quasi-spherical shape under a transmission electron microscope, with an average particle size of (509.48± 30.04) nm and an entrapment efficiency of (64.18± 1.14)%. The drug release profile demonstrated good sustained-release characteristics in vitro, and the formulation remained stable for up to 15 days when stored at 4°C. Compared to the aloperine solution group, the t1/2, AUC(0→t), AUC(0→∞), MRT(0→t), and clearance rate of the aloperine-loaded NLCs were 2.3, 2.96, 3.06, 3.03, and 0.22 times higher, respectively. This indicates that formulating aloperine into NLCs can prolong its circulation time in the body. Furthermore, the concentrations of aloperine in the lungs of the NLCs group were 1.79, 3.78, and 2.30 times higher than those in the solution group at three time points (0.25 h, 1.5 h, 4 h), suggesting that NLCs can increase the accumulation of aloperine in the lungs.Conclusion: Our findings suggest that NLCs loaded with aloperine could offer a promising strategy for the treatment of pulmonary arterial hypertension.Keywords: aloperine, nanostructured lipid carrier, aerosol inhalation, pharmacokinetics