Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ɛ-caprolactone) copolymer micelles for the delivery of curcumin

Figures & data

Scheme 1. Synthesis of LDMP.

Figure 1. FT-IR spectrum of MPEG (A), LDMP (B) and ɛ-CL (C).

Figure 2. ¹H-NMR spectrum of tetra-hydroxy MPEG (A) and LDMP (B).

Figure 3. GPC of LDMP-2.

Table 1. Characteristics of micelles.

Micelles	Feed ratio	Mw theo	Mw GPC	DPI	EE (%)	DL (%)	Mean particle (nm)
LDMP-1	1:0.5	3000	10 868	1.733	87.82 ± 3.03	10.28 ± 0.42	Precipitation
LDMP-2	1:2	6000	13 461	2.050	92.54 ± 0.54	12.84 ± 0.29	108.3 ± 13.6
LDMP-3	1:3	8000	23 942	2.016	92.53 ± 1.10	12.71 ± 0.28	146.7 ± 10.1

Mw theo, theoretical molecular weight obtained from weight ratio of MPEG and ɛ-CL charge.

Figure 4. TEM of CUR micelles (38 000×, the scale bar is 100 nm).

Figure 5. FT-IR spectrum of CUR, blank micelles and CUR micelles.

Figure 6. XRD of CUR, blank micelles and CUR micelles.

Figure 7. (A) Hemolysis test UV spectrum of different concentration of LMP, normal saline (negative control), and distilled water (positive control) and (B) percentage of hemolysis of different concentration of LDMP-2.

Figure 8. In vitro CUR-release profiles from either control solution or micelles in 40% ethanol saline solution at 37 °C [data are presented as mean ± SD (n = 3)].

Table 2. Mathematical equations for the models used to describe release characteristics of CUR from micelles.

Model	Equation	Parameter		AIC	MSC
Zero order model	QR = k0t	k0 = 1.710	0.7808	69.7396	1.0475
One order model		k1 = 0.038	0.9834	46.5249	3.6269
Higuchi model	QR = kHt^1/2	kH = 11.357	0.9612	54.1590	2.7787
Korsmeyer–Peppas model	QR = kKPt^n	kKP = 0.535 n = 0.535	0.9578	55.7022	2.6072
Hixson–Crowell model	QR = 100[1−(1−kHCt)^3]	kHC = 0.01	0.9541	55.6635	2.6115
Hopfenberg model	QR = 100[1−(1−kHBt)^n]	KHB = 0 n = 6321.872	0.9810	48.5297	3.4042
Baker–Lonsdale model		kBL = 0.003	0.9470	56.9698	2.4664
Makoid–Banakar model	QR = kMBt^ne^−^kt	kMB = 4.215 n = 0.994 k = 0.019	0.9984	27.0167	5.7945
Peppas–Sahlin model	QR = k1t^m+ k2t^2^m	k1 = 5.066 k2 = −0.079 m = 0.883	0.9969	32.9048	5.1403
Quadratic model	QR = 100(k1t^2+ k2t)	k1 = 0 k2 = 0.035	0.9911	41.6970	4.1634
Weibull model		α = 11.315 β = 0.756 Ti = 1.414	0.9918	41.5820	4.1761
Logistic model		α = −3.449 β = 2.866	0.9963	33.7019	5.0517

Figure 9. Anticancer activity of free CUR and CUR micelles on HT-29 and Hela cells in vitro after cultivation for 24 and 48 h [data are presented as mean ± SD (n = 4)].

Figure 10. Drug–time curves after i.v. injection of CUR control solution and CUR micelles [data are presented as mean ± SD (n = 6)].

Table 3. Pharmacokinetic parameters of CUR control solution and CUR micelles (n = 6).

Parameters	CUR control solution	CUR micelles
AUC0–∞ (μg/L h)	967.221	4464.601
MRT0–∞ (h)	0.199	0.327
t1/2Z (h)	0.198	1.294
CLZ (L/h/kg)	15.508	3.36
VZ (L/kg)	4.432	6.271