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Lipid- and TPGS-Based Core–Shell-Type Nanocapsules Endowed with High Paclitaxel Loading and Enhanced Anticancer Potential

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Abstract

The current study elucidates the improved drug loading of paclitaxel (PTX) in lipid- and d-α-tocopheryl polyethylene glycol succinate (TPGS)–based core–shell-type lipid nanocapsules (PTX-TPGS-LNC) for augmenting the therapeutic efficacy and curbing the toxicity. PTX-TPGS-LNCs were formulated by employing anti-solvent precipitation technique and displayed a particle size of 162.1 ± 4.70 nm and % practical drug loading of 15.04 ± 2.44%. Electron microscopy revealed that PTX-TPGS-LNCs have spherical morphology and the inner core was surrounded by a relatively lighter region, i.e., layer of lipids and TPGS. The nature of loaded PTX inside the PTX-TPGS-LNC was also confirmed using DSC and PXRD analysis. The in vitro release study showed biphasic and sustained release pattern of PTX from PTX-TPGS-LNC and it showed ~ threefold higher PTX uptake in MCF-7 cell line in comparison to free PTX. Moreover, it was apparent from the cytotoxicity assay that PTX-TPGS-LNC displayed higher cytotoxicity in MCF-7 cells and revealed ~ 2.92-fold decrease in IC50 value as against free PTX when incubated for 72 h. The apoptotic index in case of PTX-TPGS-LNC was ~ twofold higher than free PTX. The pharmacokinetic profile of PTX-TPGS-LNC revealed a ~ 3.18-fold increase in t1/2 and a ~ 2.62-fold higher AUC(0→∞) compared to Intaxel®. Finally, treatment with PTX-TPGS-LNC demonstrated significant lowering in the % tumor burden and serum toxicity markers compared to marketed formulation Intaxel®. Thus, the lipid- and TPGS-based core–shell-type LNC with high PTX loading can advance the existing standards of therapy for overshadowing cancer.

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Acknowledgements

The authors acknowledge Fresenius Kabi for providing PTX as a gift sample. The authors are also thankful to Mr. Rahul Mahajan, NIPER, S.A.S. Nagar, for his technical assistance.

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Authors and Affiliations

  1. Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Mohali, Punjab, 160062, India

    Sameer S. Katiyar, Ravindra Patil, Rohan Ghadi, Kaushik Kuche, Varun Kushwah, Chander Parkash Dora & Sanyog Jain

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  1. Sameer S. Katiyar
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  2. Ravindra Patil
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  3. Rohan Ghadi
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  4. Kaushik Kuche
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  7. Sanyog Jain
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Contributions

Sameer S. Katiyar and Ravindra Patil: responsible for conceptualizing, hypothesizing, conducting, performing, analyzing, and compiling the data for the experiments mentioned in this manuscript. Rohan Ghadi: responsible for visualizing, conceptualizing, and hypothesizing the experiments mentioned in this manuscript. Kaushik Kuche: responsible for reviewing and writing the manuscript. Varun Kushwah and Chander Parkash Dora: responsible for hypothesizing and assisting in analysis of data shown in this manuscript. Sanyog Jain: responsible for reviewing, hypothesizing, conceptualizing, and editing the final manuscript and guiding the co-authors for conducting the mentioned studies.

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Correspondence to Sanyog Jain.

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Katiyar, S.S., Patil, R., Ghadi, R. et al. Lipid- and TPGS-Based Core–Shell-Type Nanocapsules Endowed with High Paclitaxel Loading and Enhanced Anticancer Potential. AAPS PharmSciTech 23, 238 (2022). https://doi.org/10.1208/s12249-022-02389-4

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