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QbD Enabled Development and Evaluation of Pazopanib Loaded Nanoliposomes for PDAC Treatment

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal types of cancer with high mortality/incidence. Considering the crucial role of vascular endothelial growth factor (VEGF) in PDAC progression, its inhibition can be a viable strategy for the treatment. Pazopanib, a second-generation VEGF inhibitor, is approved for the treatment of various oncological conditions. However, due to associated limitations like low oral bioavailability (14–39%), high inter/intra-subject variability, stability issues, etc., high doses (800 mg) are required, which further lead to non-specific toxicities and also contribute toward cancer resistance. Thus, to overcome these challenges, pazopanib-loaded PEGylated nanoliposomes were developed and evaluated against pancreatic cancer cell lines. The nanoliposomes were prepared by thin-film hydration method, followed by characterization and stability studies. This QbD-enabled process design successfully led to the development of a suitable pazopanib liposomal formulation with desirable properties. The % entrapment of PZP-loaded non-PEGylated and PEGylated nanoliposomes was found to be 75.2% and 84.9%, respectively, whereas their particle size was found to be 129.7 nm and 182.0 nm, respectively. The developed liposomal formulations exhibited a prolonged release and showed desirable physicochemical properties. Furthermore, these liposomal formulations were also assessed for in vitro cell lines, such as cell cytotoxicity assay and cell uptake. These studies confirm the effectiveness of developed liposomal formulations against pancreatic cancer cell lines. The outcomes of this work provide encouraging results and a way forward to thoroughly investigate its potential for PDAC treatment.

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Data Availability

All the relevant data are reported within the paper and/or supplementary file. The data presented in this study are available on request to the corresponding author.

Abbreviations

ANOVA :

Analysis of variance

CCD:

Central composite design

CMA:

Critical material attributes

CPP:

Critical process parameters

CQA:

Critical quality attributes

DSPG-Na:

1,2-Distearoyl-sn-glycero-3-phospho-rac-glycerol, sodium salt

HSPC:

Hydrogenated soy phosphatidylcholine

mPEG-2000-DSPE:

N-(Carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine

PDAC:

Pancreatic ductal adenocarcinoma

PZP:

Pazopanib hydrochloride

PZP-LIP:

Pazopanib-loaded liposomes

PZP-LIP-PEG:

PEGylated pazopanib-loaded liposomes

QbD:

Quality-by-Design

QTPP:

Quality target product profile

RSM:

Response surface methodology

VEGF:

Vascular endothelial growth factor

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Acknowledgements

The author (Dr. Akash Chaurasiya) is grateful to Parenteral Drug Association, India Chapter, for extending financial support. The authors are also thankful to use the facilities at the DST-FIST facility, Department of Pharmacy and Central Analytical Laboratory at BITS Pilani, Hyderabad Campus.

Funding

This study was funded by Parenteral Drug Association, India Chapter.

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Authors and Affiliations

  1. Translational Pharmaceutics Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science, Hyderabad, Pilani, India

    Aishwarya Shinde, Kanan Panchal, Parameswar Patra, Sonali Singh, Sucharitha Enakolla & Akash Chaurasiya

  2. Nanomedicine and Bioengineering Research Laboratory, Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, India

    Rishi Paliwal

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  1. Aishwarya Shinde
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Contributions

The idea for the article was conceptualized by Akash Chaurasiya. The experimental work and data analysis was done by Aishwarya Shinde, Kanan Panchal, Sucharitha Enakolla, Sonali Singh, Parameswar Patra and was supervised by Akash Chaurasiya and Kanan Panchal. The article was drafted by Aishwarya Shinde, Kanan Panchal & Akash Chaurasiya. The article is critically reviewed and revised by Rishi Paliwal and Akash Chaurasiya.

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Correspondence to Akash Chaurasiya.

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Aishwarya Shinde and Kanan Panchal contributed equally to this paper (Co-First Authors).

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Shinde, A., Panchal, K., Patra, P. et al. QbD Enabled Development and Evaluation of Pazopanib Loaded Nanoliposomes for PDAC Treatment. AAPS PharmSciTech 25, 97 (2024). https://doi.org/10.1208/s12249-024-02806-w

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