Stereoselectivity evaluation of chiral chitosan microspheres delivery system containing rac-KET in vitro and in vivo

Figures & data

Figure 1. S-KET and R-KET plasma level after single subcutaneous injection of rac-KET suspension and microspheres at a dose of 40 mg/kg in rats. Each point represents the mean ± SD (n = 5).

Figure 2. S-KET and R-KET plasma level after single subcutaneous injection of R-KET suspension and microspheres at a dose of 40 mg/kg in rats. Each point represents the mean ± SD (n = 5).

Figure 3. S-KET plasma level after single subcutaneous injection of S-KET suspension and microspheres at a dose of 40 mg/kg in rats. Each point represents the mean ± SD (n = 5).

Table 1. S/R enantiomers ratio as a function of time for KET enantiomers released from rac-KET, R-KET suspension and microspheres (*p < .05).

Time(h)	S/R enantiomeric ratio
	R-KET microspheres	R-KET suspension	rac-KET microspheres	rac-KET suspension
1	1.32 ± 0.36	1.04 ± 0.20	2.69 ± 0.73	2.71 ± 0.40
5	2.89 ± 1.02^†	13.79 ± 5.21	4.60 ± 0.88***	17.89 ± 3.41
12	4.69 ± 1.22^†	23.28 ± 5.64	7.83 ± 1.79***	48.53 ± 19.52
24	15.43 ± 5.72	R-KET not detected	26.48 ± 18.79*	155.67 ± 112.07

Significant differences of S/R ratio between R-KET microspheres and suspensions (^†p < .001). Significant differences of S/R ratio between rac-KET microspheres and suspensions (*p < .05; ***p < .001).

Table 2. R-S conversion rate as a function of time for KET enantiomers released from R-KET, rac-KET suspension and microspheres.

Time(h)	R-S conversion rate (%)
	R-KET microspheres	R-KET suspension	rac-KET microspheres	rac-KET suspension
1	51.14 ± 7.30	45.08 ± 5.49	44.39 ± 9.24	45.69 ± 5.35
5	69.83 ± 7.59^†	91.13 ± 4.98	63.53 ± 5.96***	89.68 ± 1.92
12	79.81 ± 4.00^†	95.15 ± 1.49	76.50 ± 5.25***	97.02 ± 2.16
24	92.58 ± 2.46	99.73 ± 0.32	88.86 ± 7.64*	99.40 ± 1.15

Significant differences of R-S conversion rate between R-KET microspheres and suspensions (^†p < .001). Significant differences of R-S conversion rate between rac-KET microspheres and suspensions (*p < .05; ***p < .001). R-S conversion rate (%)= [k×(cR + cS) -cR]/(cR + cS)×k × 100%; cR: concentration of R-KET in rats; cS: concentration of S-KET in rats; k: ratio of R-KET in rac-KET.