β-Cyclodextrin Based Star-like Polymer for Loading Chlorambucil†

doi:10.7503/cjcu20180124

Abstract

Abstract:

Star-like polymer with β-cyclodextrin core(β-CD) and poly(N,N-dimethylaminoethyl methacrylate) arms(PDMAEMA), β-CD-PDMAEMA, was synthesized by atom transfer radical polymerization using brominated β-CD as initiator. The structure of the polymer was determined by Fourier transform infrared spectrophotometer(FTIR) and ¹H nuclear magnetie resonance(NMR). The polymer was used to load hydrophobic anticancer drug chlorambucil(CLB) in both ethanol and water. The loading efficiency of CLB and in vitro release performance and mechanism at 37 ℃ in buffer solutions with various pH values were investigated by UV absorption spectroscopy. The results show that, compared to that in ethanol, the hydrophobic internal cavity of β-CD in the core of the star-like polymer includes more CLB in water, which leads to higher drug loading ratio, shorter and less burst release. The release of CLB from the star-like polymer follows the diffusion mechanism. The release rate and cumulative release amount of CLB are affected by the protonation degree of PDMAEMA arms, which results to pH responsive release behavior. The acidic condition is beneficial to more efficient and sustained release of CLB.

Key words: Poly(N, N-dimethylaminoethyl methacrylate), β-Cyclodextrin;, Chlorambucil, Host-guest interaction

CLC Number:

O631.1⁺1

TrendMD:

CHEN Tao,HUANG Chan. β-Cyclodextrin Based Star-like Polymer for Loading Chlorambucil^†[J]. Chem. J. Chinese Universities, 2018, 39(10): 2350.

Figures/Tables 9

Scheme 1 Synthetic routes of star-like copolymer β-CD-PDMAEMA

Fig.1 FTIR spectra of β-CD(a), β-CD-Br(b) and β-CD-PDMAEMA(c)

Fig.2 1H NMR spectra of β-CD-Br(a) and β-CD-PDMAEMA(b) in CDCl3

Fig.3 GPC elution trace of β-CD-PDMAEMA in DMF

Fig.4 1H NMR spectra of CLB(a), β-CD-PDMAEMA(b) and β-CD-PDMAEMA/ CLB(c) in CD3OD

Fig.5 UV-Vis spectra of phenolphthalein in pH=9.4 buffer solutions of β-CD-PDMAEMA without(A) and with CLB(B)Concentration of β-CD-PDMAEMA/(mg·mL-1): a. 0.5; b. 1.0; c. 1.5; d. 2.0.

Fig.6 Release profiles of CLB from β-CD-PDMAEMA/CLB-1(A) and β-CD-PDMAEMA/CLB-2(B) in different buffer solutions at 37 ℃

Fig.7 Plots of lg(Mt/M∞) against lgt for CLB release from the β-CD-PDMAEMA/CLB-1(A) and β-CD-PDMAEMA/CLB-2(B) in different buffer solutions at 37 °Ca. pH=5.5; b. pH=7.4; c. pH=9.4.

Table 1 Release exponent(n), rate constant(lgk), and correlation coefficient(R2) for β-CD-PDMAEMA/CLB complexes

pH	β-CD-PDMAEMA/CLB-1			β-CD-PDMAEMA/CLB-2
pH	n	lgk	R²	n	lgk	R²
5.5	0.21	1.43	0.981	0.37	1.21	0.972
7.4	0.19	1.48	0.988	0.27	1.22	0.998
9.4	0.23	1.36	0.985	0.27	1.13	0.992

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