Preparation of magnetite-chitosan/methylcellulose nanospheres by entrapment and adsorption techniques for targeting the anti-cancer drug 5-fluorouracil

Figures & data

Table I. Conditions of preparation of empty nanospheres.

Formulation code	CS/MC (w/w)	Exposure time to cross-linking (min)	Concentration of cross-linking (M) × 10^2	Percentage of magnetite (%)
A1e	1/1	5	2.3	67
A2e	1/1	5	4.2	67
A3e	1/1	5	5.8	67
A4e	1/1	5	7.1	67
A5e	1/1	5	11.0	67
B1e	1/1	15	11.0	67
B2e	1/1	30	11.0	67
C1e	1/1	5	11.0	67
C2e	1/1	5	11.0	33
D1e	2/1	5	11.0	100
D2e	3/1	5	11.0	100
D3e	4/1	5	11.0	100

Table II. Formulation codes and different ingredients used in the preparation of the nanospheres.

Formulation code	Polymer ratio CS/MC (w/w)	Exposure time to cross-linking (min)	Concentration of cross-linking (M) ×10^2	Percentage of magnetite (%)	Drug/polymer ratio (w/w)	Entrapment efficiency (%)
A1	1/1	5	2.3	67	1/8	27.91
A2	1/1	5	4.2	67	1/8	41.87
A3	1/1	5	5.8	67	1/8	44.80
A4	1/1	5	7.1	67	1/8	72.40
A5	1/1	5	11.0	67	1/8	91.05
B1	1/1	15	11.0	67	1/8	82.94
B2	1/1	30	11.0	67	1/8	55.10
C1	1/1	5	11.0	33	1/8	78.13
C2	1/1	5	11.0	100	1/8	95.63
D1	2/1	5	11.0	100	1/8	96.20
D2	3/1	5	11.0	100	1/8	96.87
D3	4/1	5	11.0	100	1/8	97.43
E1	4/1	5	11.0	100	1/10	98.22
E2	4/1	5	11.0	100	1/16	99.17

Figure 1. DSC diagrams of (a) pristine MC, (b) pristine CS, (c) A_1e formulated empty nanospheres, (d) A₁ formulated nanospheres, and (e) pure 5-FU.

Figure 2. FTIR spectrum of (a) magnetite, (b) pristine CS, (c) pristine MC, (d) A_1e, (e) pure 5-FU, and (f) A_1-formulated nanosphere.

Figure 3. The zeta potentials of (a) D_3e nanospheres, (b) D₃ nanospheres, and (c) magnetite.

Figure 4. The particle size distribution of (a) D_3e, and (b) D₃ nanospheres.

Figure 5. X-ray diffractograms of (a) magnetite, and (b) A_1e nanospheres.

Figure 6. High resolution (HRTEM) images of (a) D_3e, and (b) D₃ nanospheres with 50 magnification.

Figure 7. Change of adsorption capacity with time (◊: 0.077 M 5-FU solution, : 0.038 M 5-FU solution, Δ: 0.0192 M 5-FU solution), (crosslinking concentration: 0 042 M, exposure time to crosslinking: 5 min, percent of magnetite: 67%, CS/MC (w/w): 1/1, temperature: 37°C).

Figure 8. The curve of the adsorption isotherm (crosslinking concentration: 0.058 M, exposure time to crosslinking: 5 min, percent of magnetite: 67%, adsorption time: 2 h, CS/MC (w/w): 1/1).

Figure 9. Postulated crosslinking reaction mechanisms of (a) CS, and (b) MC with GA.

Scheme 1. Schematic representation of the synthesis of IPN.

Figure 10. Effect of GA concentration on the 5-FU release in (a) encapsulation, and (b) adsorption processes. (□: A₁, ◊: A₃, □: A₅), (CS/MC ratio (w/w): 1/1, exposure time to GA: 5 min, drug/polymer ratio: 1/8, magnetite content: 67%).

Table III. The change of the entrapment efficiency with the cross-linking concentration.

Formulation code	Percent of entrapment efficiency
A1	27.91
A2	41.87
A3	44.81
A4	72.40
A5	91.05

Figure 11. Effect of exposure time to GA on the 5-FU release at (a) encapsulation and (b) adsorption processes (□: A₅, Δ:B₂), (CS/MC ratio (w/w): 1/1, crosslinking concentration: 0.11 M, magnetite content: 67%, drug/polymer ratio: 1/8).

Figure 12. Effect of magnetite content on 5-FU release for (a) encapsulation, and (b) adsorption processes (□: A₅, o: C₁, Δ: C₂), (CS/MC ratio (w/w): 1/1, crosslinking concentration: 0.11 M, exposure time to GA: 5 min, drug/polymer ratio: 1/8).

Figure 13. Effect of CS/MC ratio on 5-FU release at (a) encapsulation and (b) adsorption processes (Δ: C₂,□: D₃), (crosslinking concentration: 0.1 M, exposure time to GA: 5 min, magnetite content: 100%, drug/polymer ratio:1/8).

Table IV. Equilibrium swelling degrees for nanospheres.

Formulation code	Equilibrium swelling degree (%)
C2e	775.88 ± 3.79
D1e	806.20 ± 4.35
D2e	867.35 ± 7.33
D3e	893.86 ± 8.60

Figure 14. Effect of drug/polymer ratio on 5-FU release (□: D₃, Δ: E₁, o: E₂), (crosslinking concentration: 0.11 M, exposure time to GA: 5 min, magnetite content: 100%, CS/MC ratio (w/w): 4/1).

Table V. The k, n, and r values of CS/MC nanospheres, prepared with encapsulation and adsorption processes.

Formulation code	k	N	r	Diffusion mechanism
A1	0.0351 0.0807*	0.1810 0.1079*	0.9906 0.9846*	Case I Case I*
A2	0.1426	0.0822	0.9321	Case I
A3	0.0222 0.1203*	0.2860 0.0951*	0.9895 0.9451*	Case I Case I*
A4	0.1094	0.1607	0.9670	Case I
A5	0.1371 0.0530*	0.1674 0.1961*	0.9426 0.9937*	Case I Case I*
B1	0.1739	0.1344	0.9814	Case I
B2	0.0966 0.0917*	0.1167 0.1270*	0.9794 0.9757*	Case I Case I*
C1	0.1084	0.1840	0.8502	Case I
C2	0.2801 0.0630*	0.1029 0.1919*	0.9486 0.9911*	Case I Case I*
D1	0.0928	0.2192	0.9507	Case I
D2	0.0871	0.2395	0.9662	Case I
D3	0.1415 0.0392*	0.2012 0.2468*	0.9644 0.9981*	Case I Case I*

*Values for adsorption process.