Pazopanib-laden lipid based nanovesicular delivery with augmented oral bioavailability and therapeutic efficacy against non-small cell lung cancer

The present investigation deals with the pazopanib-loaded solid lipid nanoparticles (Pazo-SLNs) and their in-vitro and in-vivo assessments. Quality by design approach employing the Plackett-Burman and central composite design was used to identify the formulation variables, including drug/lipid ratio, organic/aqueous phase ratio, and surfactant concentration with a significant impact on the process and to fabricate a safe and efficacious novel oral dosage form of pazopanib. Particle size, drug loading, entrapment efficiency, and zeta potential of optimal Pazo-SLNs formulation were 210.03 ± 7.68 nm, 13.35 ± 0.95 %, 79.05 ± 2.55 % and −18.29 ± 1.89 mV (n = 3) respectively.

Highlights

Pazopanib loaded solid lipid nanoparticles (pazo-SLNs) were prepared & characterized.

Pazo-SLNs were optimized using the Placket-Burman & the central composite design.

Controlled release pattern and stable lyophilized powder were achieved.

Boosted cytotoxicity, high cellular uptake with augmented apoptosis in A-549 cells.

SLNs ameliorated the bioavailability of pazopanib by 9.5 folds.

FTIR study affirmed the absence of incompatibilities between the drug and the excipients. DSC and XRD measurements substantiated the amorphous form of pazopanib entrapped within the SLNs. Pazo-SLNs demonstrated high cellular uptake, showed substantial cytotoxicity to A-549 lung cancer cells due to apoptotic mode and inhibited tyrosine kinase in-vitro. Pazo-SLNs were found to be stable for three months. SLNs greatly ameliorated the pharmacokinetic behavior and bioavailability (9.5 folds) of pazopanib with a sustained-release pattern (92.67 ± 4.68 % within 24 h). A biodistribution study corroborated the lung targeting potential of Pazo-SLNs. Thus, SLNs could potentially boost the oral route efficacy of pazopanib against cancer cells.

Sameer J. Nadaf, Suresh G. Killedar, Vijay M. Kumbar, Durgacharan A. Bhagwat, Shailendra S. Gurav, Pazopanib-laden lipid based nanovesicular delivery with augmented oral bioavailability and therapeutic efficacy against non-small cell lung cancer, International Journal of Pharmaceutics, Volume 628, 2022, 122287, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2022.122287.

excipients formulation