Preparation and characterization of nimodipine-loaded nanostructured lipid systems for enhanced solubility and bioavailability

Abstract

Purpose

Nimodipine (NMP) is a clinical dihydropyridine calcium antagonist. However, the clinical application of NMP is limited by poor water solubility and low oral bioavailability. To overcome these drawbacks, this study designed optimal NMP-incorporated nanostructured lipid carriers (NLCs).

Methods

High-pressure homogenization was successfully applied to prepare NMP-NLC, and the nanoparticle morphology was observed by a transmission electron microscope. The existence form of NMP in NMP-NLC was investigated by powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy, respectively. The in vitro release study was performed by the dialysis method, and in vivo studies including in situ intestinal perfusion and pharmacokinetics were investigated in rats with NMP detected by high-performance liquid chromatography.

Results

The obtained NMP-NLC shared a spherical shape of ~70 nm with a smooth surface and high encapsulation efficiency of 86.8%±2.1%. Spectroscopy indicated that the drug was in an amorphous state. The NMP-NLC exhibited a sustained release and diverse release profiles under different release medium, which mimicked the physiological environment. Moreover, an in situ intestinal perfusion experiment revealed that NMP-NLC could be mainly absorbed by the small intestine. Remarkable improvements in C_max and AUC_0–∞ from NMP-NLC were obtained from pharmacokinetic experiments, and the relative bioavailability of NMP-loaded nanostructured lipid systems was 160.96% relative to NMP suspensions.

Conclusion

Collectively, the NLCs significantly enhanced the oral bioavailability of NMP and might provide a promising nanoplatform for hydrophobic drug delivery.

Keywords:

• nimodipine
• nanostructured lipid carriers
• increased drug solubility
• bioavailability improvement

Acknowledgments

The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (No 81573379 and 81501582), Natural Science Foundation of Jiangsu Province (No BK20171390), and National Key Research and Development Program (2017YFD0501403). This study was also supported by the Project of State Key Laboratory of Natural Medicines, China Pharmaceutical University (No SKLNMZZCX201816), the National Science and Technology Major Project (2017ZX09101001), the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_0762), and the financial support from Development Funds for Priority Academic Programs in Jiangsu Higher Education Institutions. The authors thank the Public Platform of State Key Laboratory of Natural Medicines for assistance with HPLC.

Disclosure

The authors report no conflicts of interest in this work.