Self-assembled micelles based on pH-sensitive PAE-g-MPEG-cholesterol block copolymer for anticancer drug delivery

Figures & data

Figure 1 Schematic representation of micellization of poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-g-MPEG-Chol).

Table 1 GPC and ¹H NMR data of PAE-g-MPEG-Chol and its precursors

Sample	Mna (g/mol)	Mw/Mna	Average value (calculated)b
			p	m	y
PAE	3,380	2.5
PAE-g-MPEG	5,550	2.1	1.1
PAE-g-MPEG-Chol	8,790	1.9	1.1	0	10.1

Notes:

a Determined by GPC in THF.

b Determined by the integration ratio of ¹H NMR spectra. p, m, and y mean the integration ratios of MPEG segment and cholesterol motif, respectively.

Abbreviations: GPC, gel permeation chromatography; ¹H NMR, proton nuclear magnetic resonance; M_n, average molecular weight; M_w/M_n, polydispersity index; PAE-g-MPEG-Chol, poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol; THF, tetrahydrofuran.

Figure 2 The synthetic route of poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-g-MPEG-Chol).

Figure 3 Fourier transform infrared spectra (A) of MPEG-OH and MPEG-COOH and proton nuclear magnetic resonance spectrum (B) of MPEG-COOH.

Abbreviations: MPEG-OH, methoxypoly(ethylene glycol)-hydroxyl; MPEG-COOH, methoxypoly(ethylene glycol)-carboxyl.

Figure 4 Proton nuclear magnetic resonance spectra of PAE (A), PAE-g-MPEG (B), and PAE-g-MPEG-Chol (C) in deuterated chloroform.

Abbreviations: PAE, poly(β-amino ester); PAE-g-MPEG, poly(β-amino ester)-g-poly(ethylene glycol) methyl ether; PAE-g-MPEG-Chol, poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol.

Figure 5 The potentiometric titration (A), and transmittance at 500 nm (B) of the poly(β-amino ester) (PAE) solutions dependent on the different pH values.

Figure 6 Plot of intensity ratios (I₃₃₈/I₃₃₅) as function of logarithm of the poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol concentrations (mg/mL) in different pH phosphate-buffered saline (pH 7.4 and 6.0).

Table 2 Characteristic properties of DOX-loaded PAE-g-MPEG-Chol micelles

Polymer (mg)	DOX (mg)	LC (%)	EE (%)	Particle size (nm)	PDI	Zeta potential (mV)
40	10	9.5	25.5	164	0.164	8.2
	20	28.3	60	200	0.211	10.5
	40	30.7	52.8	210	0.295	7.7

Abbreviations: PAE-g-MPEG-Chol, poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol; DOX, doxorubicin; LC, loading content; EE, entrapment efficiency; PDI, polydispersity index.

Figure 7 Particle size and zeta potential of polymeric micelles were dependent on the pH values.

Figure 8 Transmission electron microscopy micrographs of poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol micelles (pH=7.4).

Note: The right image is the magnified result of the left image.

Figure 9 In vitro drug release profiles of doxorubicin-loaded poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol micelles dependent on the pH values.

Figure 10 Free doxorubicin (DOX) and DOX-loaded poly(β-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-g-MPEG-Chol) micelles in HepG2 cells for 24 hours or 48 hours in concentration specified.