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. 2020 Sep 16;25(18):4243.
doi: 10.3390/molecules25184243.

Poly-(Lactic-co-Glycolic) Acid Nanoparticles for Synergistic Delivery of Epirubicin and Paclitaxel to Human Lung Cancer Cells

Nikita Sharma  1 , R Mankamna Kumari  1 , Nidhi Gupta  2 , Asad Syed  3 , Ali H Bahkali  3 , Surendra Nimesh  1
Affiliations

Poly-(Lactic-co-Glycolic) Acid Nanoparticles for Synergistic Delivery of Epirubicin and Paclitaxel to Human Lung Cancer Cells

Nikita Sharma et al. Molecules. .

Abstract

Combination therapy using chemically distinct drugs has appeared as one of the promising strategies to improve anticancer treatment efficiency. In the present investigation, poly-(lactic-co-glycolic) acid (PLGA) nanoparticles electrostatically conjugated with polyethylenimine (PEI)-based co-delivery system for epirubicin and paclitaxel (PLGA-PEI-EPI-PTX NPs) has been developed. The PLGA-PEI-EPI-PTX NPs exhibited a monodispersed size distribution with an average size of 240.93 ± 12.70 nm as measured through DLS and 70.8-145 nm using AFM. The zeta potential of 41.95 ± 0.65 mV from -17.45 ± 2.15 mV further confirmed the colloidal stability and PEI modification on PLGA nanoparticles. Encapsulation and loading efficiency along with in vitro release of drug for nanoparticles were done spectrophotometrically. The FTIR analysis of PLGA-PEI-EPI-PTX NPs revealed the involvement of amide moiety between polymer PLGA and PEI. The effect of nanoparticles on the cell migration was also corroborated through wound healing assay. The MTT assay demonstrated that PLGA-PEI-EPI-PTX NPs exhibited considerable anticancer potential as compared to the naïve drugs. Further, p53 protein expression analysed through western blot showed enhanced expression. This study suggests that combination therapy using PLGA-PEI-EPI-PTX NPs represent a potential approach and could offer clinical benefits in the future for lung cancer patients.

Keywords: MTT; PLGA nanoparticles; epirubicin; p53; paclitaxel.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Dose response curve for (A) Paclitaxel and (B) Epirubicin in A549 cell line as a monotherapy as well as in combination (C) at 5 fixed ratios EPI:PTX (5:1, 3:1, 1:1, 1:3, 1:5), (D) Combination index (CI) values for the combination at different fraction affected (Fa) in cancer cells. Fa represents the fraction of cells that results in cell death by the drug combination. Data shown as mean ± SD (n = 3).
Figure 2
Figure 2
Illustrative DLS spectrum and AFM images of (A) DLS spectrum of void PLGA NPs here size is 95.5 nm, (B) AFM image of void PLGA NPs here average size is 70 nm, (C) DLS spectrum of PLGA-PEI-EPI-PTX NPs here size is 241.3 nm, (D) AFM image of PLGA-PEI-EPI-PTX NPs here average size is 140 nm.
Figure 3
Figure 3
FTIR spectra of (A) void PLGA NPs, and (B) PLGA-PEI NPs and (C) PLGA-PEI-EPI-PTX NPs.
Figure 4
Figure 4
In vitro drug release study of epirubicin and paclitaxel from PLGA-PEI-EPI-PTX NPs at (A) pH 7.5 and (B) pH 5.4.
Figure 5
Figure 5
Microscopic images of cellular uptake in A549 cells, Bright field (left panel, A–C) and Fluorescence images (Right panel, D–F) of (A,D) untreated cells, (B,E) free EPI-PTX, and (C,F) PLGA-PEI-EPI-PTX NPs respectively.
Figure 6
Figure 6
Microscopic images of A549 cells for apoptosis study. (A) Untreated A549 cells demonstrated normal structure (green arrows), early apoptosis (yellow arrows) such as chromatin condensation, cell membrane blebbing were observed after treatment with, (B) Free EPI-PTX and, late apoptosis (white arrows) and necrosis (red arrows) were noticed after treatment with, and (C) PLGA-PEI-EPI-PTX NPs, respectively.
Figure 7
Figure 7
Scratch assay. (A) Microscopic images of A549 cells showing reduction of scratch at different time points, and (B) Graphical representation of the scratch at 24 h and 48 h. * p < 0.05, ** p < 0.001, *** p < 0.0001.
Figure 8
Figure 8
Cell viability as determined by MTT assay. The % cell viability of A549 cells treated with PLGA-PEI-EPI NPs, PLGA-PEI-PTX NPs, EPI-PTX only and PLGA-PEI-EPI-PTX NPs, at (A) 24 h time point, (B) 48 h time point. Data are shown as mean ± SD (n = 3).
Figure 9
Figure 9
Cell viability in HEK 293 normal cell lines as determined through MTT assay. The cells were treated with (A) void PLGA nanoparticles and with (B) PLGA-PEI-EPI-PTX NPs. Data are shown as mean ± SD (n = 3).
Figure 10
Figure 10
Western blot analysis study: A549 cells treated with EPI-PTX only and PLGA-PEI-EPI-PTX NPs, showing overexpression of p53 relative to control, and normalized protein expression. GAPDH was used as a loading control. The experiments were conducted in three replicates.
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