Formulation and characterization of bufadienolides-loaded nanostructured lipid carriers

Abstract

Objective: The aim of this study was to design bufadienolides-loaded nanostructured lipid carriers (BU-NLCs) to reduce the degradation of drugs in rat plasma. Methods: BU-NLCs were prepared by a modified melt-emulsification ultrasonic technique and then characterized by particle size distribution, zeta potential, entrapment efficiency, differential scanning calorimetry, and X-ray diffraction. Results: The optimal formulation consisted of glyceryl monostearate 1.8%, medium-chain triglyceride 0.75%, oleic acid 0.45%, Lipoid E-80® 1.5%, Pluronic F68 1.0%, and sodium deoxycholate 0.25%. The particle size distribution and the range of zeta potential of BU-NLCs were 104.1 ± 51.2 nm and −15 to −20 mV, respectively. The entrapment efficiencies of the bufadienolides were all above 85%. In the enzymolysis study, the chemical stability of cinobufagin (C) in BU-NLCs was enhanced by being encapsulated in particles of NLC and adjusting the pH of the surrounding environment to 7.0. The half-life of C was 17-fold longer than that in bufadienolides solution. The in vitro release showed that the release from BU-NLCs was slower than from bufadienolides solution and followed the Weibull equation. Differential scanning calorimetry and X-ray diffraction showed that BU-NLC was in an amorphous state after lyophilization. Conclusion: These results indicated that NLC could be developed as a carrier with improved drug plasma stability and offering controlled drug release.

Keywords:

• Bufadienolides
• differential scanning calorimetry
• enzymolysis
• in vitro release
• nanostructured lipid carriers
• X-ray diffraction

Acknowledgments

Dr. David B Jack is gratefully thanked for correcting the manuscript. We would also thank Li Zheng from the central laboratory for her kind assistance in the experimental work. We wish to acknowledge the support (Grant 06-07ZP04) of the state administration of traditional Chinese medicine of the P.R. China.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.