Paclitaxel and Erlotinib-co-loaded Solid Lipid Core Nanocapsules: Assessment of Physicochemical Characteristics and Cytotoxicity in Non-small Cell Lung Cancer

Abstract

Purpose

Lung cancer is the leading cause of cancer-related deaths. The aim of this study was to design solid lipid core nanocapsules (SLCN) comprising a solid lipid core and a PEGylated polymeric corona for paclitaxel (PTX) and erlotinib (ERL) co-delivery to non-small cell lung cancer (NSCLC), and evaluate their physicochemical characteristics and in vitro activity in NCI-H23 cells.

Methods

PTX/ERL-SLCN were prepared by nanoprecipitation and sonication and physicochemically characterized by dynamic light scattering, transmission electron microscopy, differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectroscopy. In vitro release profiles at pH 7.4 and pH 5.0 were studied and analyzed. In vitro cytotoxicity and cellular uptake and apoptosis assays were performed in NCI-H23 cells.

Results

PTX/ERL-SLCN exhibited appropriately-sized spherical particles with a high payload. Both PTX and ERL showed pH-dependent and sustained release in vitro profiles. PTX/ERL-SLCN demonstrated concentration- and time-dependent uptake by NCI-H23 cells and caused dose-dependent cytotoxicity in the cells, which was remarkably greater than that of not only the free individual drugs but also the free drug cocktail. Moreover, well-defined early and late apoptosis were observed with clearly visible signs of apoptotic nuclei.

Conclusion

PTX/ERL-SLCN could be employed as an optimal approach for combination chemotherapy of NSCLC.

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Abbreviations

ABS:

Acetate buffer solution

DDAB:

Didodecyldimethylammonium bromide

DLS:

Dynamic light scattering

DMEM:

Dulbecco’s Modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

DSC:

Differential scanning calorimetry

EGFR:

Epidermal growth factor receptor

ERL:

Erlotinib

FACS:

Fluorescence-activated cell sorting

FBS:

Fetal bovine serum

FTIR:

Fourier-transform infrared spectroscopy

GMS:

Glyceryl monostearate

HPLC:

High-performance liquid chromatography

LC:

Loading capacity

LE:

Loading efficiency

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

MWCO:

Molecular weight cut-off

NSCLC:

Non-small cell lung cancer

PBS:

Phosphate-buffered saline

PDI:

Polydispersity index

PEG:

Poly(ethylene glycol)

PTX:

Paclitaxel

SCLC:

Small cell lung cancer

SL:

Soya lecithin

SLCN:

Solid lipid core nanocapsules

TEM:

Transmission electron microscopy

TKI:

Tyrosine kinase inhibitor

XRD:

X-ray diffraction

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Acknowledgments and Disclosures

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1A2A2A01004118, 2015R1A2A2A04004806, and by the Medical Research Center Program (2015R1A5A2009124) through the NRF funded by MSIP).

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Correspondence to Chul Soon Yong or Jong Oh Kim.

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Gupta, B., Poudel, B.K., Regmi, S. et al. Paclitaxel and Erlotinib-co-loaded Solid Lipid Core Nanocapsules: Assessment of Physicochemical Characteristics and Cytotoxicity in Non-small Cell Lung Cancer. Pharm Res 35, 96 (2018). https://doi.org/10.1007/s11095-017-2337-6

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Key Words

  • Erlotinib
  • paclitaxel
  • solid lipid core nanocapsules
  • non-small cell lung cancer