HPLC method using UV visible detector at 269 nm. DSC analysis, X-ray powder diffraction and FTIR of Gemcitabine HCl, PLGA andGemcitabine HCl loaded PLGA NPs were performed. The particle sizeand zeta potential of an optimized batch were found to be 153.6 ±3.78 nm and −11.7 mV respectively. Entrapment efficiency of theoptimized batch was found to be 44%. DSC and FTIR confirmed thatthere was no interaction between drug and polymer.

The orally delivered polymeric nanoparticles of GemcitabineHCl can be an alternative to the presently available intravenousformulations by protecting the drug from hepatic degradation,delivering it directly to the systemic circulation, reducing the sideeffects and sustaining the drug release.

Fig. 1. In vitro drug release studies of plain drug solution and nanoparticles withentrapped Gemcitabine HCl.

Keywords: Polymeric nanoparticles, PLGA, Gemcitabine HCl

AcknowledgementsThe authors are thankful to All India Council of Technical Education,

New Delhi for the National Doctoral Fellowship to Garima Joshi andPurac Biomaterials, The Netherlands for the PLGA.

References[1] D.R. Kalaria, G. Sharma, V. Beniwal, M.N.V. Ravi Kumar, Design of biodegradable

nanoparticles for oral delivery of doxorubicin: in vivo pharmacokinetics andtoxicity studies, Pharm. Res. 26 (3) (2009) 493–500.

[2] G. Mittal, D.K. Sahana, V. Bharadwaj, M.N.V. Ravikumar, Estradiol loaded PLGAnanoparticles for oral administration: effect of polymer molecular weight andcopolymer composition on release behavior in vitro and in vivo, J. Control. Release119 (2007) 77–85.

doi:10.1016/j.jconrel.2013.08.070

Magnetic graphene oxide–Fe3O4 nanocomposites withdual functional properties: Drug delivery and magneticresonance imaging

Guangshuo Wang, Zhiyong Wei⁎, Lin Sang, Min Qi⁎

School of Material Science and Engineering, Dalian University ofTechnology, Dalian 116024, ChinaE-mail addresses: zywei@dlut.edu.cn (Z. Wei),minqi@dlut.edu.cn (M. Qi).

In recent years, targeted drug delivery systems have attracted moreand more attention because of their excellent clinical effects [1].Graphene oxide (GO) with its two-dimensional nanostructures andadjustable surface chemistry is an excellent candidate for targeted drugdelivery [2]. One of the promising targeting methods is using magneticnanoparticles loaded with drugs. However, there is significant interestin developing magnetically targeted carrier systems with multifunc-tional characteristics for real-time monitoring of drug distribution tothe target tissue, as well as to follow the effect of therapeutics on theprogression of the disease.

In the present study, Fe3O4/GO nanocomposites with dual functionalproperties were prepared successfully (Scheme1). The nanocomposites

possess integrated functions of chemotherapeutic drug delivery and MRimaging contrast enhancement. No obvious difference is observedbetween the WAXD patterns of Fe3O4 and Fe3O4/GO nanocomposites,indicating that the stacking of GO nanosheets remains disordered. FTIRspectra showed that two additional vibrational bands appear at around1220 and 1153 cm−1, which can be assigned to the formation of either amonodentate complex or a bidentate complex between the carboxylgroup and Fe on the surface of Fe3O4. Raman spectra revealed that G-band of Fe3O4/GO (1592 cm−1) down shifted by 5 cm−1 compared tothat of GO, which provides evidence for the charge transfer between theGO and Fe3O4. The nanocomposites exhibit a superparamagnetic statewith small remnant magnetization and coercivity at room temperature,which is desirable for MR imaging contrast enhancement. Overall, suchnovel Fe3O4/GO nanocomposites combining targeted drug delivery andMR imaging contrast enhancement will have a great potential in real-time diagnostics.

Scheme 1. Schematic representation of the fabricating process of Fe3O4/GOnanocomposites.

Keywords: Targeted drug delivery, Magnetic resonance imaging,Graphene oxide, Nanocomposites

AcknowledgementsThis work was financially supported by the National Natural

Science Foundation of China (No. 30870633, 31000427) and theFundamental Research Funds for the Central Universities.

References[1] E. Soussan, S. Cassel, M. Blanzat, I. Rico-Lattes, Drug delivery by soft matter:

matrix and vesicular carriers, Angew. Chem. Int. Ed. 48 (2009) 274–288.[2] Z. Liu, J.T. Robinson, X.M. Sun, H.J. Dai, PEGylated nanographene oxide for delivery

of water-insoluble cancer drugs, J. Am. Chem. Soc. 130 (2008) 10876–10877.

doi:10.1016/j.jconrel.2013.08.071

Thermo- and pH-sensitive CS-g-PNIPAM/CMC-g-PNIPAMpolyelectrolyte complex nanoparticles for controlled drug release

Ting Zhang, Guiying Li⁎, Lei GuoCollege of Chemistry and Materials Science, Ludong University,Yantai 264025, ChinaE-mail address: guiyingli@126.com (G. Li).

Chitosan-based polyelectrolyte complexes have attracted greatattention for their potential applications as carriers for drug delivery[1]. Recently, chitosan (CS) has been investigated as the carrier for5-fluorouracil (5-FU) by forming polyelectrolyte complex nanoparticles[2]. Compared to the pure 5-FU, the drug-loaded nanoparticles showed

Abstracts / Journal of Controlled Release 172 (2013) e14–e97e32

a sustained release in vitro. However, complexes based on chitosanshow a low response to environmental stimuli (temperature, pH orionic strength). An environmentally sensitive polyelectrolyte complexbased on CS would be highly desirable to improve the currentpolyelectrolyte complexes.

Here, we report that thermo- and pH-sensitive CS-g-PNIPAM/CMC-g-PNIPAM polyelectrolyte complex nanoparticles were designed by self-assembly of chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNIPAM)and carboxymethyl cellulose-graft-poly(N-isopropylacrylamide) (CMC-g-PNIPAM). Dynamic light scattering (DLS), transmission electronmicroscopy (TEM), and UV–vis spectroscopy revealed that highlyaggregated nanoparticles formed at a weight ratio of CS-g-PNIPAM/CMC-g-PNIPAM= 7/3 with a diameter of about 100 nm. The encapsu-lation efficiency and drug loading content of 5-FU loaded nanoparticleswas 31.34 ± 2.12% and 11.13 ± 0.66%, respectively. The polyelectrolytecomplex nanoparticles exhibited thermo- and pH-responsive drugrelease profiles (Fig. 1). Thus the novel polyelectrolyte complexnanoparticles with environmentally sensitive properties are expectedto be utilized in the field of intelligent drug delivery systems.

Fig. 1. Release profile of free 5-FU (A) and drug-loaded nanoparticles at 37 °CpH = 6.8 (B), 37 °C pH = 2.0 (C) and 25 °C pH = 6.8 (D).

Keywords: Environmental-sensitivity, 5-Fluorouracil, Nanoparticles,Polyelectrolyte complex, Sustained release

AcknowledgementsThis work was supported by the National Natural Science

Foundation of China (21074050) and the Natural Science Foundationof Shandong Province (ZR2011BQ007).

References[1] W. Sun, S.R. Mao, D. Mei, T. Kissel, Self-assembled polyelectrolyte nanoparticles

between chitosan derivatives and enoxaparin, Eur. J. Pharm. Biopharm. 69 (2008)417–425.

[2] Y.L. Zheng, W.L. Yang, C.C. Wang, J.H. Hu, S.K. Fu, L. Dong, L.L. Wu, X.Z. Shen,Nanoparticles based on the complex of chitosan and polyaspartic acid sodiumsalt: preparation, characterization and the use for 5-fluorouracil delivery, Eur. J.Pharm. Biopharm. 67 (2007) 621–631.

doi:10.1016/j.jconrel.2013.08.072

Micelles of a polymer based on amphiphilic phosphorylcholine asdrug delivery system for cancer therapy

Haibo Wang, Fangming Xu, Jian Ji⁎

Department of Polymer Science, MOE Key Laboratory of MacromoleculeSynthesis and Functionalization of Minster of Education, ZhejiangUniversity, Hangzhou 310027, ChinaE-mail address: jijian@zju.edu.cn (J. Ji).

Inspired by the cell membrane, phospholipids have been used inmany biomedical applications, such as drug carriers, gene transfec-tion agents, diagnostic agents, carriers for dyes, as well as modelsfor membrane structure and functional studies [1]. However,phospholipid layers composed of natural biomembrane componentsare dynamic and inherently unstable structures, which may pose asignificant obstacle to their use as stable, reproducible coatings andencapsulants for drugs intended for in vivo and in vitro applications[2,3]. Phospholipids are composed of a hydrophilic head and ahydrophobic tail. It is envisaged that polymerization of reactivegroups in the hydrophobic part can overcome the lack of stability.

In this study, we have successfully synthesized the polymer PMDPC(Scheme 1). The polymer can form stable micelles, which has beenverified via fluorescence spectroscopy and dynamic light scattering. Themicelles have good biocompatibility and a high drug load. Fluorescentmicrographs and flow cytometry indicated a fast internalization of theDOX-loaded micelles and efficient intracellular drug delivery. All theseresults suggested that the micelles based on PMDPC are promising as apotential intracellular anticancer drug delivery system.

Scheme 1. Synthesis of PMDPC and illustration of DOX loading in the micelles andintracellular drug release.

Keywords: Drug delivery, Phosphorylcholine, Homopolymer

AcknowledgementsFinancial support from the NSFC-50830106, National Science

Fund for Distinguished Young Scholars (51025312), the FundamentalResearch Funds for the Central Universities (2009QNA4039) andOpen Project of State Key Laboratory of Supramolecular Structureand Materials (SKLSSM200911) is gratefully acknowledged.

References[1] Y.R. Vandenburg, Z.Y. Zhang, D.J. Fishkind, B.D. Smith, Enhanced cell binding using

liposomes containing an artificial carbohydrate-binding receptor, Chem. Commun.1 (2000) 149–150.

[2] S. Liu, T.M. Sisson, M. Sisson, Synthesis and polymerization of heterobifunctionalamphiphiles to cross-link supramolecular assemblies, Macromolecules 34 (2001)465–473.

[3] D.L. Roberts, Y.N. Ma, S.E. Bowles, C.M. Janczak, J. Pyun, S.S. Saavedra, C.A. Aspinwall,Polymer-stabilized phospholipid vesicles with a controllable, pH-dependent disas-sembly mechanism, Langmuir 25 (2009) 1908–1910.

doi:10.1016/j.jconrel.2013.08.073

pH-Responsive wormlike micelles for intracellular delivery ofhydrophobic drugs

Haijun Yua, Xuetao Shib, Pengcheng Yua, Jianhua Zhoub,Zhiwen Zhanga, Hongkai Wub,⁎, Yaping Lia,⁎aShanghai Institute of Materia Medica, Chinese Academy of Sciences,Shanghai 201203, ChinabWPI-Advanced Institute for Materials Research (WPI-AIMR),Tohoku University, Sendai, JapanE-mail addresses: chhkwu@ust.hk (H. Wu),ypli@mail.shcnc.ac.cn (Y. Li).

Polymeric micelles/nanoparticles with amphiphilic propertieshave been extensively studied for solubilization and cellular deliveryof poorly water-soluble drugs or imaging contrast agents. To target

Abstracts / Journal of Controlled Release 172 (2013) e14–e97 e33