Sorafenib loaded In-situ Self-Assembling Nanoparticle: A novel approach to increasing oral bioavailability




Dong, Xiaowei


0000-0003-1150-1647 (Mans, Jaylen C.)

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Purpose: Sorafenib (SFN), a multi-kinase inhibitor, has demonstrated potent anticancer activity. However, the efficacy of orally administered SFN is limited due to its poor water solubility, leading to low absorption and bioavailability. The novel nanotechnology, In-situ Self-assembling Nanoparticles (ISNP), has shown potential to overcome low solubility in complex drug candidates. The objective of this study was to investigate ISNP nanotechnology as an approach to overcome low solubility and bioavailability of orally administered SFN. Method: SFN-ISNP granules were prepared using D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), Miglycol-12, Aeroperl-300, and SFN powder. SFN-ISNPs were characterized by particle size, drug loading (DL), entrapment efficiency (EE%) and physical structure using DLS, HPLC, and DSC analytical methods. SFN-ISNP granules were orally administered to rats, and the SFN concentrations in blood plasma and tissues were measured using LC-MS. Results: In-vitro characterization of SFN-ISNPs resulted in particle size of 181 ± 24 nm, PDI< 0.28, DL of 8.825% ± 0.36% and EE% of >99.9%(n=4). DSC analysis indicated SFN was present in an amorphous physical state within the granule. The pharmacokinetic study results demonstrate that the ISNP nanotechnology significantly increased bioavailability. Peak plasma concentration of SFN-ISNP granules resulted in 4.5-fold increase compared to SFN powder. Biodistribution results indicate that SFN-ISNP granules significantly increased SFN distribution to tissue. Conclusion: The novel ISNP drug delivery technology is a promising innovation that has demonstrated an ability to increase drug absorption and bioavailability of orally administered SFN.


Research Appreciation Day Award Winner - 2021 Graduate School of Biomedical Sciences, Department of Pharmaceutical Sciences & Pharmacotherapeutics - 2nd Place