Freeze-dried lopinavir-loaded nanostructured lipid carriers for enhanced cellular uptake and bioavailability: statistical optimization, in vitro and in vivo evaluations.

• Main Authors: Khan, Arshad Ali, Mudassir, Jahanzeb, Akhtar, Safia, Murugaiyah, Vikneswaran, Yusrida, Darwis
• Format: Article
• Language: English
• Published: MDPI 2019
• Subjects: QP Physiology
• Online Access: http://umpir.ump.edu.my/id/eprint/24708/1/Freeze-Dried%20Lopinavir-Loaded%20Nanostructured%20Lipid%20Carriers%20for%20Enhanced%20Cellular.pdf; http://umpir.ump.edu.my/id/eprint/24708/; https://doi.org/10.3390/pharmaceutics11020097; https://doi.org/10.3390/pharmaceutics11020097

Nanostructured lipid carriers (NLCs) loaded with lopinavir (LPV) were prepared by the high-shear homogenization method. The LPV-NLCs formulations were freeze-dried using trehalose as a cryoprotectant. In vitro release studies in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8) showed a burst release. The optimized freeze-dried formulation (LPV-NLC-7-Tres) had a particle size (PS), polydispersity index (PdI), zeta potential (ZP) and % entrapment efficiency (%EE) of 286.8 ± 1.3 nm, 0.413 ± 0.017, −48.6 ± 0.89 mV and 88.31 ± 2.04%, respectively. The optimized formulation observed by transmission and scanning electron microscopes showed a spherical shape. Differential scanning calorimetry study revealed the absence of chemical interaction between the drug and lipids. In vitro cellular uptake study using Caco-2 cell line showed a higher LPV uptake from LPV-NLC-7-Tres formulation compared to the free LPV-suspension. The 6-month stability study showed a minimum rise of ~40 nm in PS, while no significant changes in PdI, ZP and drug content of the LPV-NLC-7-Tres formulation stored at 5 °C ± 3 °C. The bioavailability of LPV following oral administration of LPV-NLC-7-Tres in male Wistar rats was found 6.98-fold higher than the LPV-suspension. In conclusion, the nanostructure lipid carriers are potential carriers for improving the oral bioavailability of lopinavir.