Pharmacokinetics and Biodistribution of Thymoquinone-loaded Nanostructured Lipid Carrier After Oral and Intravenous Administration into Rats

• Published in: International journal of nanomedicine 2020-01, Vol.15, p.7703-7717
• Main Authors: Zakarial Ansar, Fatin Hannani, Latifah, Saiful Yazan, Wan Kamal, Wan Hamirul Bahrin, Khong, Khei Choong, Ng, Yen, Foong, Jia Ning, Gopalsamy, Banulata, Ng, Wei Keat, How, Chee Wun, Ong, Yong Sze, Abdullah, Rasedee, Aziz, Mohd Yusmaidie
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Administration, Oral; Animals; Antioxidants (Nutrients); Benzoquinones - administration & dosage; Benzoquinones - pharmacokinetics; bioavailability; biodistribution; Biological Availability; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Delivery Systems - methods; Drug Liberation; Drug Stability; Efficiency; Hemodialysis; Hydrogenation; Lipids; Lipids - chemistry; Male; Nanoparticles; nanostructured lipid carrier; Nanostructures - administration & dosage; Nanostructures - chemistry; Nitrogen; Nuclear medicine; Original Research; Particle Size; Pharmacokinetics; Physiological aspects; Radioisotopes; Rats, Sprague-Dawley; Solubility; thymoquinone; Tissue Distribution
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S262395

Thymoquinone (TQ), an active compound isolated from , has been proven to exhibit various biological properties such as antioxidant. Although oral delivery of TQ is valuable, it is limited by poor oral bioavailability and low solubility. Recently, TQ-loaded nanostructured lipid carrier (TQ-NLC) was formulated with the aim of overcoming the limitations. TQ-NLC was successfully synthesized by the high-pressure homogenization method with remarkable physiochemical properties whereby the particle size is less than 100 nm, improved encapsulation efficiency and is stable up to 24 months of storage. Nevertheless, the pharmacokinetics and biodistribution of TQ-NLC have not been studied. This study determined the bioavailability of oral and intravenous administration of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) in rats and its distribution to organs. TQ-NLC was radiolabeled with technetium-99m before the administration to the rats. The biodistribution and pharmacokinetics parameters were then evaluated at various time points. The rats were imaged at time intervals and the percentage of the injected dose/gram (%ID/g) in blood and each organ was analyzed. Oral administration of TQ-NLC exhibited greater relative bioavailability compared to intravenous administration. It is postulated that the movement of TQ-NLC through the intestinal lymphatic system bypasses the first metabolism and therefore enhances the relative bioavailability. However, oral administration has a slower absorption rate compared to intravenous administration where the AUC was 4.539 times lower than the latter. TQ-NLC had better absorption when administered intravenously compared to oral administration. However, oral administration showed greater bioavailability compared to the intravenous route. This study provides the pharmacokinetics and biodistribution profile of TQ-NLC in vivo which is useful to assist researchers in clinical use.