Preparation and Optimization of pH-Sensitive Nintedanib Liposomes for Inhalation
10.3870/j.issn.1004-0781.2024.11.013
- VernacularTitle:吸入用pH敏感型尼达尼布脂质体的制备与优化
- Author:
Wei TIAN
1
,
2
,
3
;
Xinru WANG
;
Lingyun BAO
;
Tong LIU
;
Shujun WANG
;
Rui YANG
;
Tiantian YE
Author Information
1. 江西中医药大学药学院,南昌 330000
2. 江苏艾迪纳米生物医药有限公司制剂部,南通 226133
3. 南通市海门长三角药物高等研究院,南通 226133
- Keywords:
Nintedanib;
Idiopathic pulmonary fibrosis;
pH-sensitive liposomes;
Pulmonary inhalation preparations
- From:
Herald of Medicine
2024;43(11):1774-1781
- CountryChina
- Language:Chinese
-
Abstract:
Objective To design a pH-sensitive nintedanib liposomes(Nb-Lips)which targeted the acidic microenvironment of pulmonary fibrosis.The entrapment efficiency(EE%)was optimized by the formulation process.Methods Nintedanib liposomes were prepared by membrane hydration method,and the formulation of nintedanib liposomes were optimized by single factor experiments and response surface method(RSM).The particle size,polymer dispersity index(PDI),Zeta potential and encapsulation rate was investigated by dynamic light scattering technique and microcolumn centrifugation method.The release behavior of nintedanib liposomes in artificial lung fluid with pH 7.4 and artificial lung fluid with pH 5.3 was investigated by dialysis method.Nintedanib liposomes were atomized with a compressed air atomizer and its atomization stability and aerodynamic particle size were investigated.Results The particle size of nintedanib liposomes was(100.651±7.315)nm,the PDI was(0.328±0.026),the zeta potential was(21.633±2.004)mV,and the encapsulation rate was higher than 80%.Compared with nintedanib solution at pH 7.4,the total release of nintedanib liposomes in pH 5.3 artificial lung solution was 60.78%higher,and the release of nintedanib liposomes in pH 5.3 artificial lung solution was 48h delayed,which was much higher than that of nintedanib solution.The data reveals no significant differences in particle size,potential and PDI before and after atomization of nintedanib liposomes,and the encapsulation rate decreased 4.25%.The fine particle fraction of the atomized droplets was 37.49%.Conclusion The response surface method can effectively improve the encapsulation rate of nintedanib liposomes,and successfully prepare nintedanib liposomes that are sensitive to acidic environment,and can be inhaled and released slowly.
