Fabrication and Medical Imaging of Ultrasonic Imaging Nanocaspsules†

doi:10.7503/cjcu20130690

Abstract

Abstract:

Poly(lactic acid)-b-poly(ethylene glycol)(MePEG-b-PLA) based nanocapsules containing per-fluorohexane were fabricated through a double emulsion-solvent evaporation method. In the preparation, three kinds of hydrophilic polymers, i.e., poly(vinyl-alcohol)(PVA), chitosan(CS), and carboxymethyl dextran(CMG) were used as emulsifier or co-emulsifier to modify the surface of nanocapsules. Besides, two kinds of MePEG-b-PLA copolymers with different block length ratio were used as main shell composition to fabricate nanocapsules. Nanocapsule size, morphology, zeta potential, water stability of six nanocapsule samples fabricated by different polymers or emulsifiers were characterized by Malvern nanosizer analyzer, transmission electron microscope(TEM) and UV-Visible spectrophotometer(UV-Vis), respectively. The results showed that nanocapsules using 1%PVA+1%CMG as an emulsifier and MePEG-b-PLA[m(MePEG)∶m(PLA)=1∶3] as shell material had monodispersed small size and stable water property. These nanocapsules are not only in nanometer-scale but also possess favorable ultrasonic imaging property. Ultrasonic imaging property of nanocapsules was charaeterized using in vitro ultrasound tester and made a comparison with a commercialized ultrosonic imaging agent SonoVue^TM. The results demonstrated a brighter contrast scale and edurable ultrasonic property of MePEG-b-PLA nanocapsules. In addition, the cytotoxicity by incubating MePEG-b-PLA nanocapsules with rat liver cells line BRL-3A was characterized through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. The results showed that the PLA-based nanocapsules imposed no significant inhibition effect on proliferation of BRL-3A cells.

Key words: Nanocapsule, Ultrasonic imaging, Double emulsion-solvent evaporation, Poly(lactic acid)-b-poly(ethylene glycol), Emulsifier

CLC Number:

TrendMD:

HUANG Chaofan, QU Guanxiong, WEI Zhenhua, XU Bin, DING Jing, DOU Hongjing, SUN Kang. Fabrication and Medical Imaging of Ultrasonic Imaging Nanocaspsules^†[J]. Chem. J. Chinese Universities, 2014, 35(1): 191.

Figures/Tables 10

Scheme 1 Double emulsion/solvent evaporation process in the fabrication of nanocapsules

Table 1 Formula of nanocapsules different in emulsifier and mass fraction of MePEG and PLA

Sample	m(MePEG)∶m(PLA)	Mass fraction of emulsifier
FC1	1∶9	0.5%PVA
FC2	1∶9	1%PVA+1%CMG
FC3	1∶9	1%PVA
FC4	1∶9	0.5%PVA+0.5%CS
FC5	1∶3	1%PVA
FC6	1∶3	0.5%PVA+0.5%CS

Table 2 Average diameter of nanocapsule

Sample	Average diameter/nm	PDI
FC1	689.2	0.154
FC2	432.9	0.213
FC3	449.3	0.251
FC4	971.0	0.344
FC5	485.4	0.604
FC6	618.2	0.243

Fig.1 Nanoparticles diameter distribution of FC2

Fig.2 TEM images of FC2 saturated by phosphotungstic acid(A) and RuO4(B)

Fig.3 Normalized UV-Vis absorbance of FC1(a), FC2(b), FC3(c), FC4(d), FC5(e) and FC6(f) in water

Fig.4 Zeta Potentials of nanocapsules in water

Fig.5 Comparison of ultrasound contrast effect between FC2(A1,B1), SonoVueTM(A2,B2) and deionized water(A3,B3) at beginning(A) and 40 min(B)

Fig.6 Normalized grey scale of FC2(a) and SonoVueTM(b) relative to deionized water

Fig.7 Cytotoxicity profiles of BRL-3A cell, when incubated with FC2 nanocapsules as determined by MTT assay

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