Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon

Figures & data

Figure 1. Scanning electron photomicrographs of crosslinked dextran microspheres.

Table 1. Effect of fabrication variables on mean diameter, entrapment efficiency and in vitro drug release of uncoated GA crosslinked dextran microspheres.

Formulation code	Variables	Values	Mean diameter (µm)	% Drug entrapment	In vitro drug release after 8 h (%)
GD-MW1	Molecular weight	40 000 Da	08.54 ± 0.25	81.62 ± 1.59	99.40 ± 1.47
GD-MW2*		70 000 Da	14.62 ± 0.50	84.91 ± 1.80	92.69 ± 3.03
GD-MW3		200 000 Da	23.17 ± 0.74	89.54 ± 2.05	90.63 ± 2.95
GD-P1	Drug:polymer	1:2	09.45 ± 0.34	79.41 ± 1.73	97.78 ± 2.82
GD-P2*		1:3	15.52 ± 0.71	83.39 ± 2.84	91.47 ± 2.41
GD-P3		1:4	20.71 ± 0.84	86.53 ± 1.71	89.32 ± 3.31
GD-G1	Amount of crosslinking agent (GA)	2 mL	19.37 ± 0.77	83.87 ± 1.13	97.70 ± 2.09
GD-G2*		3 mL	15.46 ± 0.58	80.53 ± 3.53	91.60 ± 3.36
GD-G3		4 mL	11.51 ± 0.29	75.34 ± 4.36	89.03 ± 3.91
GD-S1	Stirring rate	1000 rpm	19.63 ± 0.54	85.34 ± 2.35	89.32 ± 3.61
GD-S2*		2000 rpm	13.47 ± 0.31	81.62 ± 2.54	92.34 ± 2.80
GD-S3		3000 rpm	10.45 ± 0.24	78.89 ± 2.65	96.41 ± 3.25
GD-C1	Stirring time	2 h	18.56 ± 0.79	78.82 ± 1.28	97.79 ± 2.74
GD-C2*		3 h	15.34 ± 0.81	82.53 ± 2.32	92.79 ± 2.95
GD-C3		4 h	14.36 ± 0.44	76.23 ± 1.90	91.88 ± 2.57

All the values represents mean ± SD (n = 3); *optimized parameter for final formulation.

Figure 2. Effect of molecular weight on drug release from crosslinked dextran microspheres (bars represent mean ± SD, n = 3).

Figure 3. Scanning electron photomicrographs of Eudragit-S-100-coated crosslinked dextran microspheres.

Table 2. Particle size and entrapment efficiency of various Eudragit-coated crosslinked dextran microspheres.

Polymer	Coat:core ratio	Particle size (µm)	% Entrapment efficiency
Eudragit S-100	4:1	154.58 ± 4.81	75.79 ± 2.73
Eudragit S-100	8:1	184.40 ± 7.36	71.55 ± 3.63

All the values represents mean ± SD (n = 3).

Figure 4. DSC thermogram of (a) 5-FU (b) dextran (c) GA crosslinked dextran microspheres (d) Eudragit-S-100 (8:1) coated 5-FU-loaded crosslinked dextran microspheres.

Figure 5. In vitro drug release from coated dextran microspheres (bars represent mean ± SD, n = 3).

Figure 6. In vitro drug release from coated dextran microspheres in the presence of dextranase (bars represent mean ± SD, n = 3).

Figure 7. In vitro drug release from coated dextran microspheres in the presence of 2% rat cecal contents (bars represent mean ± SD, n = 3).

Table 3. Pharmacokinetic parameters of 5-FU after administration of plain 5-FU solution and 5-FU-loaded coated dextran microspheres in rats.

Parameters	Plain 5-FU solution	Coated dextran microspheres
Cmax (µg/mL)	30.61 ± 1.56	14.27 ± 1.03*
Tmax (h)	1.0 ± 0.15	12.0 ± 1.65*
Kel (h^−1)	1.119 ± 0.12	0.077 ± 0.004*
t1/2 (h)	0.62 ± 0.25	8.97 ± 1.37*
AUC0–∞ (µg/h/mL)	55.77 ± 3.01	128.34 ± 7.20*
MRT (h)	1.69 ± 0.30	14.49 ± 1.55*
BA	–	2.33

Mean ± S.D. (n = 3); *p ≤ 0.05; MRT- Mean residence time, AUC- Area under the curve, BA- Relative bioavailability.

Figure 8. Organ distribution of plain 5-FU solution and 5-FU-loaded coated dextran microspheres after oral administration (bars represent mean ± SD, n = 3).