Synthesis and Drugloading Properties of Dual Thermo and Redox Sensitive P(NIPAM-AA) Nnanogels†

doi:10.7503/cjcu20150580

Chem. J. Chinese Universities ›› 2015, Vol. 36 ›› Issue (12): 2563.doi: 10.7503/cjcu20150580

• Polymer Chemistry • Previous Articles Next Articles

Synthesis and Drugloading Properties of Dual Thermo and Redox Sensitive P(NIPAM-AA) Nnanogels^†

ZHAN Yuan¹, HE Peixin¹, SUN Zhengguang¹, YI Panpan¹, ZHANG Weili¹, ZHANG Yuhong^1,^*(), LI Yulin^2,^*()

1. Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials,Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education,College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China
2. Key Laboratory for Ultrafine Materials of Ministry of Education,East China University of Science and Technology, Shanghai 200237, China

Received:2015-07-23 Online:2015-12-10 Published:2015-11-17
Contact: ZHANG Yuhong,LI Yulin E-mail:zhangyuhong@hubu.edu.cn;yulinli@ecust.edu.cn
Supported by:
† Supported by the National Nature Science Foundation of China(No.51203047), the Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education, China(No.2014-KL-004), the Shanghai Municipal Natural Science Foundation, China(No.15ZR1408500) and 111 Project, China(No.B14018)

Abstract

Abstract:

Although doxorubicin(DOX) has been widely used in the treatment of different types of cancer, the multi-drug resistance is still a bottle for its further clinical applications. Nanogels with high loading capacity, good stability, environmental responsiveness(such as ionic strength, pH, temperature, reducing agent), are promising therapeutic nanocarriers for targeting delivery of drugs in a controllable way. In this study, a series of thermo- and redox- sensitive P(NIPAM-AA) nanogels was developed by free radical precipitation polymerization of N-isopropylacrylamide(NIPAM) and acrylic acid(AA) as monomers in the presence of N,N'-bis(acryloyl)cystamine(BAC) as crosslinking agent. The structures, particle size, Zeta potential, morphology, encapsulation efficiency and drug cumulative release[using doxorubicin(DOX) as an anticancer model drug] of the prepared composite nanogels were characterized by FTIR, Raman spectrum, dynamic light scattering(DLS), scanning electron microscopy(SEM) and ultraviolet-visible(UV-Vis) techniques. DLS study showed that BAC concentrations had great influence on thermo-sensitivity of nanogels as well as their Zeta potentials. UV-Vis study showed that when concentration of BAC was 1.6 and 0.32 mmol/L, nanogels had good drug encapsulation efficiency(64.9% and 53.5%, respectively). In vitro release study showed that temperature controlled DOX release was not obviously(DOX cumulative release at 4 h was 56% and 58% at 25 and 37 ℃, respectively) for the 0.32 mmol/L BAC-crosslinking system, probably because of the loose structure of the nanogels at low crosslinking degree that allows for rapid DOX diffusion from the nanogels at both temperatures. When BAC concentration was increased to 1.6 mmol/L, DOX cumulative release at 4 h was 56% and 61% at 25 and 37 ℃, respectively. The release rate can be further accelerated in a medium mimicking the intracellular reductive environment(37 ℃ and in the presence of 4 mmol/L D,L-dithiothreitol). The nanogels with good thermo- and redox-sensitivity can act as a good platform for delivery of various kinds of therapeutics, beyond anticancer drugs.

Key words: N,N'-Bis(acryloyl)cystamine, Free radical precipitation polymerization, Redox sensitive, Nanogels

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ZHAN Yuan, HE Peixin, SUN Zhengguang, YI Panpan, ZHANG Weili, ZHANG Yuhong, LI Yulin. Synthesis and Drugloading Properties of Dual Thermo and Redox Sensitive P(NIPAM-AA) Nnanogels^†[J]. Chem. J. Chinese Universities, 2015, 36(12): 2563.

Figures/Tables 6

Scheme 1 Schematic representation of the formation and drug release behavior of DOX-loaded PNA nanogels

Fig.1 FTIR spectra of PNA/DOX nanogels(a), PNA nanogels(b), DOX(c), the mixture of DOX and PNA nanogels(d)

Fig.2 Raman spectra of pure BAC(a) and PNA nanogels(b)

Fig.3 Effects of crosslinker concentration on size(A) and Zeta potential(B) of PNA nanogels

Fig.4 SEM images of PNA-1.6(A) and PNA/DOX-1.6(B)

Fig.5 In vitro DOX cumulative release in PBS buffer from PNA/DOX-0.32(A) and PNA/DOX-1.6 in the presence of 4 mmol/L DTT(B)

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Synthesis and Drugloading Properties of Dual Thermo and Redox Sensitive P(NIPAM-AA) Nnanogels^†

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