PEGylation alleviates the non-specific toxicities of Alpha-Momorcharin and preserves its antitumor efficacy in vivo

Figures & data

Figure 1. Serum concentration–time profiles of α-MMC and α-MMC-PEG in SD rats after a single iv bolus injection.

Table 1. Pharmacokinetic parameters of α-MMC and α-MMC-PEG in serum of SD rats after a single iv bolus injection.

	α-MMC		α-MMC-PEG
Non-compartmental analysis	0.5 mg/kg	2.0 mg/kg	0.5 mg/kg	2.0 mg/kg
Cmax(μg/L)	4879	16 599.57	11 091.3	38 174.03
Elimination t1/2 (h)	7.53	6.283	52.065	86.892
MRT (h)	19.061	15.838	26.711	28.29
CL(L/h/kg)	0.123	0.123	0.002	0.003
Vd(L/kg)	0.049	0.046	0.049	0.047
AUC(0−t)(ug/L × h)	4505.021	17 685.63	195 558.015	713 876.319
AUC(0−∞) (ug/L × h)	5156.72	19 142.2	206 042.921	714 547.291

Figure 2. Antitumor effects of repeated ip dose of α-MMC or α-MMC-PEG against EMT-6 mouse mammary carcinoma tumor in male Balb/C mice. Eight mice were used for each group. (A) body weight. (B) Tumor growth, expressed as the mean ± SD of relative tumor volume (%). ‘*’– p < 0.05, compared to control group.

Table 2. Antitumor activity of α-MMC and α-MMC-PEG on EMT-6 rat breast cancer in vivo (x ± s; n = 8).

	Animal number		Body weight of animal (g)
Dose (mg kg^−1)	Before treatment	After treatment	Before treatment	After treatment	Terminal RTV/%	T/C%
Saline	8	8	18.85 ± 0.86	25.28 ± 0.66	1743.17 ± 284.60	–
3.0 mg/kg as α-MMC	8	0	19.12 ± 0.64	–	–	–
1.0 mg/kg as α-MMC	8	8	19.11 ± 0.67	15.93 ± 0.77	710.20 ± 232.00^a	38.56
0.33 mg/kg as α-MMC	8	8	19.27 ± 0.56	21.75 ± 0.77	1452.40 ± 122.89	89.85
3.0 mg/kg as α-MMC-PEG	8	8	19.17 ± 0.74	21.08 ± 0.56	312.45 ± 154.00^a	25.18
1.0 mg/kg as α-MMC-PEG	8	8	19.34 ± 0.71	23.82 ± 0.77	617.64 ± 189.34^ab	35.43
0.33 mg/kg as α-MMC-PEG	8	8	19.26 ± 0.58	23.19 ± 0.54	1613.22 ± 258.00^c	92.55

^ap < 0.05 versus saline-treated group (control); ^bp > 0.05 versus α-MMC(1.0 mg/kg); ^cp > 0.05 versus α-MMC(0.33 mg/kg).

Figure 3. Antitumor effects of repeated ip dose of α-MMC or α-MMC-PEG against MDA-MB-231 human mammary carcinoma tumor in female Balb/C nude mice. Eight mice were used for each group. (A) body weight. (B) Tumor growth, expressed as the mean ± SD of relative tumor volume (%). ‘*’– p < 0.05, compared to control group.

Table 3. Antitumor activity of α-MMC and α-MMC-PEG on MDA-MB-231 human breast cancer in vivo (x ± s; n = 8).

	Animal number		Body weight of animal (g)
Dose (mg kg^−1)	Before treatment	After treatment	Before treatment	After treatment	Terminal RTV/%	T/C%
Saline	8	8	19.89 ± 0.63	26.36 ± 1.46	1179.69 ± 110.02	–
3.0 mg/kg as α-MMC	8	0	19.70 ± 0.72	–	–	–
1.0 mg/kg as α-MMC	8	8	19.56 ± 0.69	14.76 ± 1.24	428.25 ± 49.37^a	36.3
0.33 mg/kg as α-MMC	8	8	19.82 ± 0.66	16.11 ± 1.49	973.74 ± 181.50	82.54
3.0 mg/kg as α-MMC-PEG	8	8	19.63 ± 0.73	21.68 ± 1.48	248.60 ± 40.13^a	21.07
1.0 mg/kg as α-MMC-PEG	8	8	19.67 ± 0.71	22.34 ± 1.37	470.43 ± 85.99^ab	39.88
0.33 mg/kg as α-MMC-PEG	8	8	19.73 ± 0.68	25.63 ± 1.35	1043.51 ± 118.33^c	88.46

^ap < 0.05 versus saline-treated group (control); ^bp > 0.05 versus α-MMC(1.0 mg/kg); ^cp > 0.05 versus α-MMC(0.33 mg/kg).