Polyethylene sebacate doxorubicin nanoparticles: role of carbohydrate anchoring on in vitro and in vivo anticancer efficacy

Figures & data

Figure 1. SEM images of (A) NPs, (B) Pul NPs, (C) AGn NPs, and (D) Pul–AGn NPs.

Figure 2. FTIR spectra.

Figure 3. (A) Differential scanning calorimetry thermograms and (B) powder X-ray diffraction crystallographs of (1) Dox, (2) Gantrez® AN 119, (3) PES, (4) NPs, (5) Pul NPs (6) AGn NPs, and (7) Pul–AGn NPs.

Figure 4. In vitro release of Dox from various Dox formulations (mean ± S.D.; n = 3). (A) Phosphate buffer, pH 7.4. (B) Acetate buffer, pH 5.5.

Table 1. Kinetic models for in vitro drug release.

	Model	Zero order			First order			Higuchi			Korsmeyer–Peppas
Dox formulation	Release media/pH	r^2	Slope	Intercept	r^2	Slope	Intercept	r^2	Slope	Intercept	r^2	Slope	Intercept
Dox solution	PBS 7.4	0.842	1.047	2.23	0.662	0.05	0.419	0.883	5.609	−2.51	0.947	0.713	0.446
	Acetate buffer 5.5	0.592	3.07	29.55	0.489	0.025	1.48	0.806	16.58	18.28	0.924	0.407	1.48
NPs	PBS 7.4	0.853	1.07	2.18	0.663	0.052	0.403	0.898	5.74	−2.7	0.962	0.74	0.429
	Acetate buffer 5.5	0.911	2.21	5.33	0.721	0.048	0.805	0.977	11.85	−4.61	0.986	0.661	0.837
Pul NPs	PBS 7.4	0.858	1.08	2.16	0.628	0.055	0.359	0.915	5.86	−2.85	0.961	0.807	0.378
	Acetate buffer 5.5	0.34	2.35	5.09	0.769	0.047	0.826	0.976	12.48	−5.27	0.919	0.613	0.875
AGn NPs	PBS 7.4	0.915	1.21	3.29	0.48	0.051	0.496	0.970	6.41	−1.93	0.821	0.795	0.495
	Acetate buffer 5.5	0.916	2.19	5.04	0.728	0.048	0.785	0.979	11.73	−4.81	0.975	0.665	0.82
Pul-AGn NPs	PBS 7.4	0.956	2.6	0.82	0.619	0.049	0.54	0.965	6.81	−2.25	0.979	0.735	0.56
	Acetate buffer 5.5	0.929	2.46	6.14	0.670	0.048	0.853	0.993	13.15	−4.77	0.991	0.691	0.874

NPs, PES Gantrez® AN 119 Dox NPs; Pul NPs, pullulan-anchored NPs; AGn NPs, Arabinogalactan-anchored NPs; Pul-AGn NPs, Pul-AGn-anchored NPs.

Figure 5. (A) In vitro hemolysis and (B) In vitro serum stability of Dox nanoparticles (mean ± S.D.; n = 3).

Figure 6. Plasma concentration versus time profiles of Dox following intravenous administration of Dox formulations (mean ± S.D.; n = 6).

Table 2. Pharmacokinetic parameters of Dox solution, NPs, and carbohydrate-anchored NPs.

	Treatment groups
Pharmacokinetic parameters	Dox solution	NPs	Pul NPs	AGn NPs	Pul–AGn NPs
Cmax (μg/ml)	2.75 ± 0.071	4.9 ± 0.08	5.38 ± 0.11	5.1 ± 0.092	5.69 ± 0.06
Tmax (h)	0.083	0.083	0.083	0.083	0.083
Slope	−0.045 ± 0.012	−0.0127 ± 0.001	−0.0135 ± 0.001	−0.0125 ± 0.002	−0.114 ± 0.001
Kel (h^−1)	0.103 ± 0.028	0.029 ± 0.003	0.031 ± 0.003	0.029 ± 0.005	0.026 ± 0.006
t1/2 (h)	6.67 ± 1.43	23.674 ± 2.08	22.23 ± 3.29	23.98 ± 4.54	26.19 ± 1.02
AUC 0–24 h (μg-h/ml)	5.005 ± 0.403	50.052 ± 0.59	52.263 ± 1.41	51.293 ± 1.07	56.824 ± 0.85
AUC 0–∞ (μg-h/ml)	5.31 ± 0.282	97.59 ± 4.61	96.596 ± 11	100.124 ± 13.6	116.58 ± 3.72
Cl (ml/h) 0–24 h	249.738 ± 119.4	24.97 ± 1	23.91 ± 2.25	24.37 ± 2.72	21.99 ± 2.25
Cl (ml/h) 0–∞	235.008 ± 73.32	12.8 ± 2.88	12.94 ± 5.88	12.48 ± 8.9	10.72 ± 1.67
Vd (ml) 0–24 h	2403.373 ± 3674	853.147 ± 269.5	767.144 ± 388.5	843.419 ± 677	831.37 ± 175
Vd (ml) 0–∞	2261.615 ± 3046.7	437.558 ± 57.02	415.059 ± 34.2	432.0831 ± 114	405.233 ± 68

Figure 7. In-vitro cytotoxicity of Dox solution, NPs, and carbohydrate-anchored NPs in MCF-7 cell lines at 50 μg/ml of Dox (mean ± standard error, n = 3).

Figure 8. Tumor growth suppression in mice treated with Dox formulations (mean ± S.D.; n = 6).

Figure 9. Representative histopathological images of heart, kidney, liver, lung, spleen, and brain of mice treated with (A) control; (B) blank NPs; (C) Dox solution; (D) NPs; (E) Pul NPs; (F) AGn NPs; (G) Pul–AGn NPs.