(M1130-07-38) Evaluation of Surface-Modified PLGA Nanoparticles to Enhance Absorption of Sorafenib for the Treatment of Liver Cancer

Purpose: Sorafenib tosylate (SFN) belongs to the BCS class II drug with low solubility and undergoes first-pass metabolism, which leads to reduced bioavailability of 38% [1]. Due to the lack of tumor specificity, oral-systemic administration of sorafenib often leads to high toxicity and severe side effects. For this reason, the approach to nanoparticles (NPs) and surface modification needs for overcome the limitation of SFN. Polylactide-co-glycolide (PLGA) has advantageous advantages for water-soluble and poorly-soluble drug delivery, and has low toxicity, biodegradability and controlled release. it has sustained-release properties, so it can be continuously supplied to the body for a long period of time, and absorption can be improved through solubilization of the drug [2].

Methods: SFN-PLGA NPs were prepared by solvent evaporation and D-α-tocopherol polyethylene glycol (TPGS) or chitosan (75-85% deacetylated) was used for biomimetic surface modification. Formulations were prepared according to the amount of PLGA, and formulations of SFN-PLGA-NPs were evaluated through size, zeta potential, polydispersity index, drug loading, encapsulation rate and drug release pattern. Differential scanning calorimetry, X-ray diffraction and Fourier transform infrared spectroscopy were used to evaluate the physicochemical properties of SFN-PLGA-NPs.

Results: The particle size of SFN-PLGA NPs prepared with PVA and TPGS was 178 to 236 nm, and the zeta potential ranged from -10 to -32 mV. The size of SFN-PLGA NPs prepared with chitosan was 387 to 559.3 nm, and the zeta potential was 54 to 78 mV, confirming that it was changed by chitosan. It was confirmed that SFN was encapsulated in the PLGA NPs in an amorphous form through DSC, XRD, and FT-IR. The encapsulation efficiency showed different patterns depending on the surface modification, and the highest encapsulation efficiency was 80.82% for SFN-PLGA NPs, 83.78% for SFN-PLGA NPs-TPGS, and 79.29% for SFN-PLGA NPs-chitosan. The drug release pattern showed a cumulative release amount of 24.16% to 51.09% for 5 days in all groups, confirming sustained release. The absorption of SFN-PLGA NPs will be evaluated in further study.

Conclusion: Overall, this study confirmed that PLGA NPs could be a viable strategy for sustained targeting delivery of SFN in vivo.

References: 1. .Pamu Sandhya 1, Pamu Poornima 2, Darna V R N Bhikshapathi , Self Nanoemulsifying Drug Delivery System of Sorafenib Tosylate: Development and In Vivo Studies, Pharm Nanotechnol, 2020;8(6):471-484.
2. Bala, Indu, Sarita Hariharan, and MNV Ravi Kumar. "PLGA nanoparticles in drug delivery: the state of the art." Critical Reviews™ in Therapeutic Drug Carrier Systems 21.5 (2004).