Preparation and characterization of 6-mercaptopurine-coated magnetite nanoparticles as a drug delivery system

Figures & data

Figure 1 X-ray diffraction patterns for iron oxide (A) and iron oxide coated with chitosan and 6-mercaptopurine (FCMP) (B). Inset shows X-ray diffraction pattern for pure chitosan (C) and pure 6-mercaptopurine (D).

Figure 2 Fourier transform infrared spectra for (A) iron oxide nanoparticles, (B) chitosan, (C) iron oxide nanoparticles coated with chitosan, (D) pure 6-mercaptopurine, and (E) FCMP, iron oxide nanoparticles coated with chitosan and 6-mercaptopurine.

Table 1 Magnetic properties of Fe₃O₄ magnetite nanoparticles and FCMP

Samples	Ms (emu/g)	Mr (emu/g)
Fe3O4	29.091	1.098
FCMP	17.497	0.365

Abbreviations: FCMP, iron oxide nanoparticles coated with chitosan and 6-mercaptopurine; M_r, remanent magnetization; M_s, saturation magnetization.

Figure 3 Magnetization plots of (A) iron oxide magnetite nanoparticles and (B) iron oxide nanoparticles coated with chitosan and 6-mercaptopurine.

Notes: The data is presented in terms of M, mass magnetization (emu/g), versus H, applied magnetic field (Oe).

Figure 4 Thermogravimetry analyses of (A) 6-mercaptopurine and (B) iron oxide nanoparticles coated with chitosan and 6-mercaptopurine.

Note: The red arrows point to the weight loss.

Figure 5 Transmission electron micrographs for (A) iron oxide magnetite nanoparticles (200 nm bar), (B) iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (200 nm bar), particle size distribution of iron oxide nanoparticles (C) and particle size distribution of iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (D).

Figure 6 (A) Release profiles for physical mixtures of 6-mercaptopurine and (B) 6-mercaptopurine from iron oxide nanoparticles coated with chitosan and 6-mercaptopurine dissolved in hot ethanol into (I) phosphate-buffered solution at pH 4.8, (II) phosphate-buffered solution at pH 7.4, and (C) release profiles for 6-mercaptopurine from the iron oxide nanoparticles containing the same amounts of chitosan and 6-mercaptopurine dissolved in dimethyl sulfoxide into (III) phosphate-buffered solution at pH 4.8 and (IV) phosphate-buffered solution at pH 7.4.

Table 2 Correlation coefficient, rate constant, and elimination half-life obtained by fitting the data for release of MP and MP-D from FCMP and FCMP-D into phosphate-buffered solution at pH 4.8 and pH 7.4

			R ^2
Sample	Aqueous solution	Saturated release %	Pseudo-first order	Pseudo-second order	Parabolic diffusion	Rate constant (K) (mg/min)	t1/2 (min)
FCMP	pH 4.8	93.2	0.9624	0.9914	0.7380	a6.73 × 10^−4	14
FCMP	pH 7.4	50.6	0.5055	0.9965	0.6839	b3.52 × 10^−3	5
FCMP-D	pH 4.8	97.7	0.4853	0.9385	0.6255	c2.65 × 10^−4	42
FCMP-D	pH 7.4	55.4	0.8743	0.1109	0.8154	d1.25 × 10^−4	5,529

Notes:

a,b,c Estimated using pseudo-second order kinetics

d estimated using first order kinetics.

Abbreviations: FCMP, iron oxide nanoparticles coated with chitosan and 6-mercaptopurine dissolved in hot ethanol; FCMP-D, iron oxide nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but dissolved in dimethyl sulfoxide; MP, 6-mercaptopurine dissolved in hot ethanol; MP-D, 6-mercaptopurine dissolved in dimethyl sulfoxide; t_1/2, elimination half-life.

Figure 7 Fitting the data for 6-mercaptopurine release from iron oxide nanoparticles coated with chitosan and 6-mercaptopurine dissolved in hot ethanol into different solutions to the pseudo-second order kinetics for pH 4.8 (A) and pH 7.4 (B) and fitting data of 6-mercaptopurine released from the iron oxide nanoparticles coated with chitosan and 6-mercaptopurine dissolved in dimethyl sulfoxide into different solutions to the pseudo-second order kinetics for pH 4.8 (C) and first order kinetics for pH 7.4 (D).

Abbreviations: t, time; q_t, release at time t.

Figure 8 Viability assays for (A) normal mouse fibroblast (3T3) and (B) leukemia (WEHI-3) cell lines and anticancer activity of FCMP, FCMP-D, FNPs, and pure 6-MP, respectively, after 72 hours of treatment. The IC₅₀ was 4.94 ± 0.76 μg/mL, 11.94 ± 0.45 μg/mL, 47.56 ± 2.13 μg/mL, and 0.60 ± 0.18 μg/mL for cancer cells exposed to FCMP, FCMP-D, FNPs, and pure 6-MP, respectively.

Abbreviations: FCMP, iron oxide coated with chitosan and 6-mercaptopurine; FNPs, iron oxide nanoparticles; FCMP-D, iron oxide nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but dissolved in dimethyl sulfoxide; Conc, concentration; IC₅₀, half maximal inhibitory concentration; 6-MP, 6-mercaptopurine.