A novel pH–enzyme-dependent mesalamine colon-specific delivery system

Figures & data

Figure 1 Scanning electron microscopy of mesalamine-coated microparticles.

Note: Magnification, ×3,500.

Figure 2 In vitro release profiles of different mesalamine formulations.

Notes: Release experiments were carried out in 0.1 N HCl (2 hours), PBS at pH 7.4 (3 hours), and PBS at pH 6.8 (20 hours), at 37°C±0.5°C. Each point represents the mean value of three different experiments ± SD. ×, mesalamine-coated microparticles; Δ, mesalamine suspensions; n=3.
Abbreviations: PBS, phosphate-buffered saline; SD, standard deviation.

Table 1 Pharmacokinetic parameters of mesalamine after oral administration of mesalamine-coated microparticles and mesalamine suspensions to rats (n=6)

Parameter	Oral administration
	Suspensions	Coated microparticles
Tmax (hours)	1.7±0.8	8.3±1.5*
t1/2 (hours)	2.8±1.2	16.2±3.7*
Cmax (µg/mL)	12.6±1.8	6.4±1.3*
AUC0–t (µg·h/mL)	40.7±5.2	71.9±8.3*
AUC0–∞ (µg·h/mL)	46.3±6.4	88.6±9.3*
MRT (hours)	5.3±1.7	13.5±3.2*
CL (L/hours)	21.3±4.7	5.1±1.8*

Notes:

* P<0.05 for mesalamine-coated microparticles and mesalamine suspensions. Data shown as mean ± standard deviation.

Abbreviations: T_max, the amount of time that a drug is present at the maximum concentration in serum; t_1/2, half-life; C_max, maximum serum concentration; AUC_0–t, area under the plasma concentration–time curve from 0 hours to time; AUC_0–∞, area under the plasma concentration–time curve from 0; MRT, mean residence time; CL, clearance.

Figure 3 Plasma concentration–time profiles of mesalamine in rats after oral administration of mesalamine-coated microparticles and mesalamine suspensions (n=6).

Table 2 The AUC_{0–24 h} of mesalamine in stomach, small intestine, and colon after intragastric administration of coated microparticles and suspensions to mice (n=6)

Formulation	Stomach	Small intestine	Colon
Suspensions (µg·h/g), mean ± SD	137.5±12.3	146.7±16.4	71.2±8.1
Coated microparticles (µg·h/g), mean ± SD	55.3±4.6	90.3±8.2	187.2±24.3
Ratioa	0.4	0.62	2.63*

Notes:

a The ratio was AUC (coated microparticles)/AUC (suspensions);

* P<0.05 for coated microparticles vs suspensions.

Abbreviations: AUC_{0–24 h}, area under the plasma concentration–time curve from 0 to 24 hours; SD, standard deviation.

Figure 4 Distribution of drugs in tissues of mice following intragastric administration of a single 10 mg/kg dose of mesalamine-coated microparticles and mesalamine suspensions.

Notes: Each point represents mean ± SD of six rats. The solid lines indicate mesalamine-coated microparticles and the dotted lines indicate mesalamine suspensions.
Abbreviation: SD, standard deviation.

Figure 5 The images of hematoxylin and eosin staining tissue sections of mice after intragastric administration of mesalamine-coated microparticles and mesalamine suspensions.

Notes: Mesalamine-coated microparticles: (A) stomach, (B) small intestine, and (C) colon. Mesalamine suspensions: (D) stomach, (E) small intestine, and (F) colon. Magnification, ×500.