Abstract
The present study aimed to prepare stable dl-tetrahydropalmatine (dl-THP) nanosuspensions of optimized formulation with PEGylated chitosan as a multifunctional stabilizer using the antisolvent precipitation method. A central composite design project of three factors and five-level full factorial (53) was applied to design the experimental program, and response surface methodology analysis was used to optimize the experimental conditions. The effects of critical influencing factors such as PEGylated chitosan concentration, operational temperature, and ultrasonic energy on particle size and zeta potential were investigated. Under the optimization nanosuspension formulation, the particle size was 269 nm and zeta potential was at 37.4 mV. Also, the dl-THP nanosuspensions maintained good physical stability after 2 months, indicating the potential ability of the multifunctional stabilizer for stable nanosuspension formulation. Hence, the present findings indicated that PEGylated chitosan could be used as the ideal stabilizer to form a physically stable nanosuspension formulation.
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Abbreviations
- dl-THP:
-
dl-Tetrahydropalmatine
- QbD:
-
Quality-by-design
- DoE:
-
Design of experiments
- CCD-RSM:
-
Central composite design-response surface methodology
- PEG-Chs:
-
PEGylated chitosan
- DMF:
-
N,N-Dimethylformamide
- PHA:
-
Phthalic anhydride
- SOCl2 :
-
Thionyl chloride
- NaH:
-
Sodium hydride
- THF:
-
Tetrahydrofuran
- FT-IR:
-
Fourier-transformed infrared spectroscopy
- PDI:
-
Polydispersity index
- SEM:
-
Scanning electron microscope
- TEM:
-
Transmission electron microscope
- AFM:
-
Atomic force microscope
- DSC:
-
Differential scanning calorimeter
- PXRD:
-
Powder X-ray diffraction
- SD:
-
Standard deviations
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Acknowledgements
This work was supported by the Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources (2060302) and the Natural Science Foundation Program of Shandong Province (no. ZR2012HM071).
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Yan, B., Wang, Y., Wang, L. et al. Design and synthesis of a novel multifunctional stabilizer for highly stable dl-tetrahydropalmatine nanosuspensions and in vitro study. Appl Nanosci 8, 1285–1297 (2018). https://doi.org/10.1007/s13204-018-0811-z
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DOI: https://doi.org/10.1007/s13204-018-0811-z