Immunosafety and chronic toxicity evaluation of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) polymer micelles for paclitaxel delivery

Figures & data

Figure 1. ¹H-NMR spectrum of mPEG-PLA (40/60) (A); CMC of mPEG-PLA (40/60) (B) and (50/50) (C) at 25 °C; size distribution of mPEG-PLA (40/60) (D); mPEG-PLA (40/60)-BSA (E); size distribution of PTX-PM by intensity (F) and number (G); TEM images of blank copolymer micelle (H) and PTX-PM (I).

Table 1. Characteristics of a series of mPEG-PLA blank micelles and PTX-PM.

Parameters	mPEG-PLA 40/60	mPEG-PLA 50/50	PTX-PM
EE (%)	–	–	97.73 ± 4.6
DL (wt%)	–	–	16.89 ± 3.0
CMC (μg/mL)	1.30 ± 0.15	2.4 ± 0.12	–
Particle size (nm)
Aqueous   solution	36.7 ± 0.6	44.0 ± 0.9	35.2 ± 1.6
BSA	40.2 ± 3.3	71.4 ± 4.9	–
Zeta potential (mV)
0 h	−1.1 ± 0.26	–	0.7 ± 0.39
12 h after	4.0 ± 0.81	–	−0.4 ± 0.14

Data are represented as $\overline{X}\pm SD$ (n = 3).

Figure 2. In vitro drug release profile of paclitaxel polymeric micelles.

Figure 3. The hemolysis rate of mPEG-PLA 40/60, 50/50 and Cr EL in 50% ethanol (n = 3).

Figure 4. (A) Effect of mPEG-PLA (40/60), mPEG-PLA (50/50), PTX-PM and Cr EL on complement activation in vitro. n = 3, $\overline{x}$ ± SD. *p < 0.05, **p < 0.01 versus negative control. #p < 0.05, ##p < 0.01 versus Cr EL in 50% ethanol. (B) Effect of mPEG-PLA (40/60), PTX-PM and Cr EL on β-hexosaminidase releasing of RBL-2H3 cells. n = 3, $\overline{x}$ ± SD. *p < 0.05 versus negative control.

Table 2. The body weight ($\overline{x}$ ± SD, n = 6 kg).

Groups	Beginning	One week	Two weeks	Three weeks	Four weeks
Positive control	7.17 ± 0.73	6.74 ± 0.53^a	7.17 ± 0.58^b	7.13 ± 0.64^b	7.03 ± 0.57^b
Negative control	6.7 ± 0.88	6.78 ± 0.91	6.88 ± 1.01	7.03 ± 1.15	7.1 ± 1.17
mPEG-PLA (40/60)	6.83 ± 1.03	6.90 ± 1.00	6.95 ± 0.88	6.88 ± 0.93	6.83 ± 0.98
mPEG-PLA (50/50)	7.15 ± 0.63	7.05 ± 0.88	7.26 ± 0.80	7.16 ± 0.71^c	7.04 ± 0.84^c

^an = 5.

^bn = 3.

^cn = 4.

Table 3. Important organ index ($\overline{x}$ ± SD, g/kg).

Organs	Positive control (n = 3)	Negative control (n = 6)	(40/60) (n = 6)	(50/50) (n = 4)
Brain	9.63 ± 0.73	12.69 ± 0.87	10.45 ± 1.28	12.19 ± 2.77
Liver	45.85 ± 6.49*	36.47 ± 1.62	36.11 ± 6.99	37.77 ± 6.71
Lung	8.40 ± 1.35	8.40 ± 1.55	8.25 ± 1.15	8.97 ± 2.24
Kidney	6.06 ± 1.33	5.06 ± 0.43	5.08 ± 0.40	4.95 ± 0.36
Thymus	0.46 ± 0.19*	0.89 ± 0.76	0.84 ± 0.38	0.68 ± 0.30
Ovary	0.20 ± 0.10*	0.083 ± 0.048	0.19 ± 0.11*	0.039 ± 0.016*
Testis	1.35 ± 0.55	1.036 ± 0.142	1.14 ± 0.63	1.39 ± 0.20

*p < 0.05, compared with the negative control group.