Construction of paclitaxel-loaded poly (2-hydroxyethyl methacrylate)-g-poly (lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer nanoparticle delivery system and evaluation of its anticancer activity

Figures & data

Figure 1 Fourier transform infrared spectra of (A) PHEMA, (B) PHEMA-PLA, (C) PHEMA-PLA-pNP, and (D) PHEMA-g-(PLA-DPPE).

Abbreviations: PHEMA, poly (2-hydroxyethyl methacrylate; PLA, poly (lactide)-1; DPPE, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine; pNP, 4-nitrophenyl chloroformate.

Figure 2 ¹H NMR spectra of (A) PHEMA, (B) PHEMA-PLA, and (C) PHEMA-PLA-DPPE, and (D) ³¹P NMR spectrum of (E) DPPE and PHEMA-g-(PLA-DPPE) copolymer.

Abbreviations: PHEMA, poly (2-hydroxyethyl methacrylate; PLA, poly (lactide)-1; NMR, nuclear magnetic resonance; DPPE, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine; pNP, 4-nitrophenyl chloroformate.

Figure 3 Schematic illustration of paclitaxel encapsulation into nanoparticles with the PHEMA-g-(PLA-DPPE) copolymer by emulsion/solvent evaporation (A) and transmission electron microscopy and dynamic light scattering characterization of empty and paclitaxel-loaded nanoparticles made by the emulsion/solvent evaporation method (B). Transmission electron microscopic image (a) and dynamic light scattering histogram, (b) of empty nanoparticles; transmission electron microscopic image (c) and dynamic light scattering histogram (d) of paclitaxel-loaded nanoparticles.

Abbreviations: PHEMA, poly (2-hydroxyethyl methacrylate; PLA, poly (lactide)-1; DPPE, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine.

Table 1 Effects of formulation parameters on size, size distribution, loading content of paclitaxel, and encapsulation efficiency of paclitaxel-loaded PHEMA-g-(PLA-DPPE) nanoparticles

Copolymer:drug ratio	100:1	70:1	50:1
0.5%PVA
Mean diameter (nm)	239.8 ± 2.1	249.2 ± 1.6	257.3 ± 3.1
PDI	0.114 ± 0.006	0.133 ± 0.008	0.189 ± 0.011
EE (%)	53.90 ± 1.4	57.30 ± 1.2	67.00 ± 2.3
LC (%)	0.60 ± 0.15	0.98 ± 0.17	1.65 ± 0.13
1%PVA
Mean diameter (nm)	250.0 ± 2.3	259.5 ± 3.1	269.0 ± 4.0
PDI	0.106 ± 0.004	0.151 ± 0.012	0.243 ± 0.010
EE (%)	48.00 ± 1.2	51.00 ± 1.7	63.00 ± 2.5
LC (%)	0.52 ± 0.13	0.85 ± 0.12	1.34 ± 0.16
2%PVA
Mean diameter (nm)	269.2 ± 3.4	295.6 ± 2.5	301.2 ± 2.2
PDI	0.211 ± 0.013	0.224 ± 0.009	0.253 ± 0.120
EE (%)	42.40 ± 2.1	50.60 ± 1.9	61.00 ± 2.4
LC (%)	0.39 ± 0.11	0.67 ± 0.13	1.18 ± 0.12

Abbreviations: PHEMA, poly (2-hydroxyethyl methacrylate; PLA, poly (lactide)-1; DPPE, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine.

Figure 4 (A) Accumulative release profiles of paclitaxel and paclitaxel-loaded nanoparticles at different pH values (copolymer/drug 100:1, polyvinyl alcohol 0.5%). (B) Effects of PHEMA-g-(PLA-DPPE) nanoparticles on erythrocyte morphology. Control: erythrocyte morphology in normal mice blood (a); erythrocyte morphology in mice after receiving blank PHEMA-g-(PLA-DPPE) nanoparticle treatment via intraperitoneal injection (b); erythrocyte morphology of mice blood after incubating the blood with a final concentration of 5 mg/mL PHEMA-g-(PLA-DPPE) copolymers for 3 hours (c), erythrocyte morphology of mice blood after incubating the blood with a final concentration of 15 mg/mL PHEMA-g-(PLA-DPPE) copolymer for 3 hours.

Abbreviations: PHEMA, poly (2-hydroxyethyl methacrylate; PLA, poly (lactide)-1; DPPE, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine.

Figure 5 (A) Inhibition of cancer cell proliferation by free paclitaxel and paclitaxel-loaded PHEMA-PLA-DPPE nanoparticles. Inhibition of MCF-7 cell proliferation by free paclitaxel, paclitaxel-loaded nanoparticles, or empty nanoparticles after 48 hours of incubation at 37°C. The concentration of empty nanoparticles used was equal to the concentration of paclitaxel-loaded nanoparticles. Tumor volume (B) and tumor weight (C) of MCF-7 tumor-bearing female nude mice treated with saline, paclitaxel, or paclitaxel-loaded PHEMA-g-(PLA-DPPE) nanoparticles. Data are presented as the mean ± standard deviation (n = 4). (D) Representative images of excised tumors from mice treated with saline, free paclitaxel, or paclitaxel-loaded PHEMA-g-(PLA-DPPE) nanoparticles.

Abbreviations: PHEMA, poly (2-hydroxyethyl methacrylate; PLA, poly (lactide)-1; DPPE, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine.

Schema 1 Synthetic route for (A) PHEMA-PLA, (B) PHEMA-PLA-pNP, and (C) PHEMA-g-(PLA-DPPE).

Abbreviations: PHEMA, poly (2-hydroxyethyl methacrylate; PLA, poly (lactide)-1; DPPE, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine; pNP, 4-nitrophenyl chloroformate.

Figure S1 ¹³C NMR spectra of PHEMA (A), PHEMA-PLA (B), and PHEMA-g-(PLA-DPPE) copolymers (C).

Abbreviations: PHEMA, poly (2-hydroxyethyl methacrylate; PLA, poly (lactide)-1; DPPE, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine.

Figure S2 Thermogravimetric analysis profiles of (A) PHEMA, (B) PHEMA-PLA, and (C) PHEMA-g-(PLA-DPPE) copolymers.

Abbreviations: PHEMA, poly (2-hydroxyethyl methacrylate; PLA, poly (lactide)-1; DPPE, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine.