Hydrogels are water swollen hydrophilic polymer networks andexist as a form of semi-solid. Injectable thermogels refer to systems thatcan be dissolved in water or PBS to form a sol in vitro while forming aphysical hydrogel at body temperature after injection [1,2]. Due to thespontaneous gelation, injectable thermogels have been widely used inthe fields of drug release and tissue engineering [3–5]. As drug releasecarriers, injectable thermogels are a kind of ideal local drug deliverysystems, which can provide sustained or controlled release of drugs,enhance efficacy, reduce side effects and dosage times, thus improvingpatient compliance. Copolymers composed of hydrophilic PEG andhydrophobic polyesters like PLA, PCL, and PGA and their copolymershave drawn special attention as injectable thermogel materials becauseof their good biodegradability and biocompatibility [6–8]. In this study,we prepared a PCLA–PEG–PCLA thermogel system loaded withibuprofen as a sustained delivery drug depot. Ibuprofen, an inhibitorof cyclooxygenase, is a kind of common nonsteroidal anti-inflammatorydrug (NSAID), which is widely used to treat rheumatic arthritis andosteoarthritis. The sol–gel–sol phase transition behavior showed thatsynthesized PCLA–PEG–PCLA block copolymer could change from thesol to the gel phase around physiological temperatures. In vitro drugrelease experiments indicated that after an initial burst of about16% ibuprofen was released in an almost zero order in three days. Soit is concluded that PCLA–PEG–PCLA thermogel is a good carrier foribuprofen to achieve a sustained release.

Keywords: Injectable hydrogel, Thermogelling block copolymer,Controlled release, Ibuprofen

AcknowledgementsThe group (Professors Ding and Yu) was supported by the

Chinese Ministry of Science and Technology (973 Programs No.2009CB930000 and No. 2011CB606203), and NSF of China (GrantsNo. 50903021, No. 21034002, and No. 91127028).

References[1] B. Jeong, Y.H. Bae, D.S. Lee, S.W. Kim, Biodegradable block copolymers as injectable

drug-delivery systems, Nature 388 (1997) 860–862.[2] L. Yu, J.D. Ding, Injectable hydrogels as unique biomedical materials, Chem. Soc.

Rev. 37 (2008) 1473–1481.[3] L. Yu, G.T. Chang, H. Zhang, J.D. Ding, Injectable block copolymer hydrogels for

sustained release of a PEGylated drug, Int. J. Pharm. 348 (2008) 95–106.[4] Z. Zhang, J. Ni, L. Chen, L. Yu, J. Xu, J.D. Ding, Biodegradable and thermoreversible

PCLA–PEG–PCLA hydrogel as a barrier for prevention of post-operative adhesion,Biomaterials 32 (2011) 4725–4736.

[5] G.T. Chang, T.Y. Ci, L. Yu, J.D. Ding, Enhancement of the fraction of the activeform of an antitumor drug topotecan via an injectable hydrogel, J. Control. Release156 (2011) 21–27.

[6] L. Yu, H. Zhang, J.D. Ding, A subtle end-group effect onmacroscopic physical gelationof triblock copolymer aqueous solutions, Angew. Chem. Int. Ed. 45 (2006) 2232–2235.

[7] Z. Zhang, Y.X. Lai, L. Yu, J.D. Ding, Effects of immobilizing sites of RGD peptidesin amphiphilic block copolymers on efficacy of cell adhesion, Biomaterials 31(2010) 7873–7882.

[8] L. Yu, Z. Zhang, J.D. Ding, Influence of LA and GA sequence in the PLGA block on theproperties of thermogelling PLGA–PEG–PLGA block copolymers, Biomacromolecules12 (2011) 1290–1297.

doi:10.1016/j.jconrel.2013.08.141

The in vitro anti-tumor effect of MTX–Fe3O4–PLLA–PEG–PLLAmicrospheres prepared by suspension-enhanced dispersion bysupercritical CO2

Tingting Danga, Aizheng Chena,b, Shibin Wanga,b,⁎, Yuangang Liua,baCollege of Chemical Engineering, Huaqiao University,Xiamen 361021, ChinabInsititute of Biomaterials and Tissue Engineering, Huaqiao University,Xiamen 361021, ChinaE-mail addresses: mumiantt@163.com (T. Dang),sbwang@hqu.edu.cn (S. Wang).

Magnetic targeted drugs are the fourth generation of targetedreagents, which would dramatically increase the anticancer drugs'therapeutic efficacy, reduce the drugs' toxic side effects and increase thepatient's compliance [1]. As new drug formulations, it is necessary toevaluate its effectiveness and safety before entering clinical trials stage[2]. In the present research, usingMG-63human osteosarcoma cells, thein vitro anti-tumor activity of methotrexate-loaded Fe3O4-poly(L-lacticacid)-poly(ethylene glycol)-poly(L-lactic acid) magnetic compositemicrospheres (MTX–Fe3O4–PLLA–PEG–PLLA, MMCMs) repeatedly pre-pared in a process of suspension-enhanced dispersion by supercriticalCO2 (SpEDS) [3] was evaluated at a cellular level, including the Alamarblue assay, acridine orange-ethidium bromide (AO/EB) fluorescencestaining, prussian blue staining, flow cytometry test, etc. The in vitrocytotoxicity experiments indicated that MMCMs had a better anti-proliferation activity in a dose-dependent and time-dependent mannerthan the free MTX formulations. Apoptotic morphological changescould be detected more significantly in treated groups than in theuntreated groups. Furthermore, the rapid accumulation of MMCMs andthe direct visualization of their uptake by cells were observed. Finally,the investigation of the cell cycle analysis using standard propidiumiodide staining showed that the number of cells in the S phase increasedsignificantly for the treated groups, indicating an arrest of the cell cyclein the S phase. The results reveal that the MMCMs have an elevatedin vitro cytotoxicity and can induce apoptosis in MG-63 cells, which isencouraging for continued research of anti-tumor activity in vivo andimplies their great potential of application in targeted cancer therapy.

Fig. 1. (A) The inhibition rate curves (F-B: Free MTX, MTX nanoparticles, MMCMsprepared by co-precipitation and microencapsulation, Blank MCMs), (B) photos ofAO/EB staining (×400) of MG-63 cells co-cultured with MMCMs.

Keywords: Methotrexate, Anti-tumor effect, Cell apoptosis, Magnetictargeting, Supercritical CO2

AcknowledgementsFinancial supports fromNSFC (51103049, 81171471 and 31170939)

are gratefully acknowledged

References[1] J. Chomoucka, J. Drbohlavova, D. Huska, V. Adam, R. Kizek, J. Hubalek, Magnetic

nanoparticles and targeted drug delivering, Pharmacol. Res. 62 (2010) 144–149.[2] A.Z. Chen, X.F. Lin, S.B. Wang, L. Li, Y.G. Liu, L. Ye, G.Y. Wang, Biological evaluation of

Fe3O4-poly(L-lactide)-poly(ethyleneglycol)-poly(L-lactide) magnetic microspheresprepared in super-critical CO2, Toxicol. Lett. 212 (2012) 75–82.

[3] A.Z. Chen, L. Li, S.B. Wang, X.F. Lin, Y.G. Liu, C. Zhao, G.Y. Wang, Z. Zhao, Study ofFe3O4–PLLA–PEG–PLLA magnetic microspheres based on supercritical CO2: prepara-tion, physicochemical characterization, and drug loading investigation, J. Supercrit.Fluids 67 (2012) 139–148.

doi:10.1016/j.jconrel.2013.08.142

Pore structure of temperature-sensitive superporous hydrogelsand the absorption and release of baicalin

Tingting Zhang, Qing-song Zhang, Rui Xue, Yiting ChenSchool of Materials Science and Engineering, Tianjin PolytechnicUniversity, State Key Laboratory of Hollow Fiber Membrane Materialsand Processes, Tianjin 300387, China

Abstracts / Journal of Controlled Release 172 (2013) e14–e97 e69