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

  • Biki Gupta
  • Bijay Kumar Poudel
  • Shobha Regmi
  • Shiva Pathak
  • Hima Bindu Ruttala
  • Milan Gautam
  • Gyeong Jin An
  • Jee-Heon Jeong
  • Han-Gon Choi
  • Chul Soon Yong
  • Jong Oh Kim
Research Paper
  • 126 Downloads

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.

Key Words

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

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

Notes

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).

Compliance with Ethical Standards

Conflict of Interest

The authors have no conflict of interest to declare.

Supplementary material

11095_2017_2337_MOESM1_ESM.docx (1.2 mb)
ESM 1 (DOCX 1178 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.College of PharmacyYeungnam UniversityGyeongsanSouth Korea
  2. 2.College of Pharmacy, Institute of Pharmaceutical Science and TechnologyHanyang University,AnsanSouth Korea

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