International Journal of Nanomedicine (Dec 2018)
Preparation and characterization of nimodipine-loaded nanostructured lipid systems for enhanced solubility and bioavailability
Abstract
Zaijin Teng,1,* Miao Yu,1,* Yang Ding,1,* Huaqing Zhang,1 Yan Shen,1 Menglao Jiang,1 Peixin Liu,1 Yaw Opoku-Damoah,2 Thomas J Webster,3 Jianping Zhou1 1Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; 2Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia; 3Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA *These authors contributed equally to this work 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 Cmax and AUC0–∞ 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
