Rivaroxaban-loaded SLNs with treatment potential of deep vein thrombosis: in-vitro, in-vivo, and toxicity evaluation

Abstract

Objectives

Rivaroxaban (RXB), a novel Xa inhibitor having groundbreaking therapeutic potential. However, this drug is associated with few limitations, including its pharmacokinetics related toxicities. Here, we developed RXB-loaded SLNs (RXB-SLNs) to improve its biopharmaceutical profile. Methods: High pressure homogenizer was used to prepare RXB-SLNs, followed by their particle characterization, Transmission electron microscopy (TEM), Dynamic light scattering (DSC), and Powder X-ray diffraction (PXRD) analysis. Beside this, in-vitro, ex-vivo, and in-vivo evaluation, prothrombin time assessment and toxicity was investigated.

Results

RXB-SLNs had their particle size in nano range (99.1 ± 5.50 nm) with excellent morphology and low polydispersity index (0.402 ± 0.02) and suitable zeta potential (−25.9 ± 1.4 mV). The incorporation efficiency was observed around 95.9 ± 3.9%. In-vitro release profiles of the RXB-SLNs exhibited enhanced dissolution (89 ± 9.91%) as compared to pure drug (11 ± 1.43%) after 24 h of the study. PK study demonstrated a seven times enhanced bioavailability of RXB-SLNs when compared with pure drug. Furthermore, RXB-SLNs exhibited an expressive anti-coagulant behavior in human and rat blood plasma. Also, the final formulation exhibited no toxicity after oral administration of the SLNs.

Conclusions

All together, these studies revealed the capability of the SLNs for carrying the RXB with enhanced therapeutic efficacy and no toxicity, most importantly for the treatment of deep vein thrombosis.

Keywords:

• Rivaroxaban (RXB)
• solid lipid nanoparticles (SLNs)
• deep vein thrombosis (DVT)
• bioavailability
• toxicity

Acknowledgement

The authors acknowledge Higher Education Commission (HEC) Pakistan for funding this study.

Ethics statement

Animal studies reported in this study were as per the approved ethical guidelines of NIH and ARRIVE guidelines and were duly recommended by the ethical commission of animal testing, Quaid-I-Azam University Islamabad Pakistan with the endorsement no QAU/FBS/2021-324.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The research work was funded by HEC through its grant No: 20-14604/NRPU/R&D/HEC/2021.