Nano-encapsulated metformin-curcumin in PLGA/PEG inhibits synergistically growth and hTERT gene expression in human breast cancer cells

Figures & data

Table 1. Characterization of PLGA/PEG amphiphilic copolymers and drug-loaded NPs.

Groups	Particle size (nm)^a	Polydispersity	Zeta potential (mV)^a
PLGA/PEG NPs	202 ± 9.23	0.176	−7.23 ± 0.43
Met-loaded PLGA/PEG NPs	209 ± 10.56	0.166	−6.1 ± 2.2
Cur-loaded PLGA/PEG NPs	223 ± 10.43	0.132	−5.7 ± 2.4
Met–Cur-loaded PLGA/PEG NPs	257 ± 11.38	0.112	−3.2 ± 1.2

^a Measured using dynamic light scattering (DLS). Nanoparticles were prepared by directly dissolving copolymers or drug-loaded n in distilled water at a concentration of .5 mg/ml followed by 10 min sonication. Results means ± SD (n = 3).

Figure 1. Dynamic light scattering (DLS), Transmission electron microscopy (TEM) and Field emission scanning electron microscopy (FESEM) characterization of Met–Cur–PLGA/PEG NPs showing the core-shell structure of NPs. (A) DLS histogram of Met–Cur NPs, (B) TEM and (C) FE-SEM images.

Figure 2. Infrared spectra of (A) Cur NPs and (B) Met NPs (C) Met–Cur NPs.

Figure 3. Stability of Met–Cur PLGA/PEG NPs in different pH as judged by their diameter.

Figure 4. Drug release profiles of free Met, free Cur and Met and Cur from PLGA/PEG NPs in PBS at pH 7.4. The data are presented as mean ± SD (n = 3).

Figure 5. In vitro cytotoxicity of free Met, free Cur, free Met–Cur and Met–Cur–PLGA/PEG NPs against T47D cells incubated for 72 h. The cytotoxicity of formulations was evaluated by MTT assay. The data are presented as mean ± SD (n = 3).

Figure 6. Synergistic effects of free Met–Cur (A) and Met–Cur–PLGA/PEG NPs (B) on T47D cell proliferation. CI =1, additive effect; CI <1, synergistic effect; CI >1, antagonistic effect. Data represented are from three independent experiments.

Figure 7. Real-time PCR analysis. Cur–PLGA/PEG (A) and Met–PLGA/PEG (B) inhibited hTERT expression in higher concentration (8 and 8000 μm) compared to pure components (p < .05). Whereas Met–Cur and Met–Cur–PLGA/PEG NPs decreased hTERT mRNA expression in in a dose dependent manner (C). Nano-combination in relative to free combination could further decline in hTERT expression in all concentration (p < .05).