D. Qu et al. / Carbohydrate Polymers 92 (2013) 545–554
553
with the previous papers (Wang, Tiruppathi, Cho, Minshall, & Malik,
2011).
Li, L., Wartchow, C. A., Danthi, S. N., Shen, Z., Dechene, N., Pease, J., et al. (2004).
A novel antiangiogenesis therapy using an integrin antagonist or anti-FLK-1
antibody coated 90 Y-labeled nanoparticles. International Journal of Radiation
Oncology Biology and Physics, 58, 1215–1227.
Li, Q., Yang, D., Ma, G., Xu, Q., Chen, X., Lu, F., et al. (2009). Synthesis and char-
acterization of chitosan-based hydrogels. International Journal of Biological
Macromolecules, 44, 121–127.
4. Conclusions
In this paper, OPHPC and FA-OPHPC were designed and syn-
thesized. The chemical structures and some physical properties
were characterized by 1H NMR, 13C NMR, FT-IR, elemental anal-
ysis, WAXD, GPC and TGA. The CMC and solubility of OPHPC in
water and organic solvents were improved by introducing phthalyl
groups. PTX-OPHPC with small particle size and narrow distribu-
tion were prepared, which showed that the apparent solubility of
PTX was increased by 4000-fold in comparison with that of free
PTX in aqueous medium. OPHPC and FA-OPHPC showed nearly
noncytotoxicity against L-O2 cells. In the cellular studies, PTX-
FA-OPHPC significantly improved the uptake of PTX compared
with PTX-OPHPC and Taxol®. Furthermore, we also illustrated
that folate moieties exhibited a direct impact on the internaliza-
tion mechanism. PTX-FA-OPHPC entered MCF-7 cells via folate
receptor-mediated and caveolae-mediated pathways, while the
internalization of PTX-OPHPC via clathrin-mediated and caveolae-
mediated pathways were observed. In conclusion, it suggested that
PTX-OPHPC exhibited significant enhancement on cellular uptake
and PTX-FA-OPHPC displayed a good active targeting ability to
MCF-7 cells.
Liu, J., Li, H., Jiang, X., Zhang, C.,
& Ping, Q. (2010). Novel pH-sensitive
chitosan-derived micelles loaded with paclitaxel. Carbohydrate Polymers, 82,
432–439.
Liu, C., Yu, W., Chen, Z., Zhang, J., & Zhang, N. (2011). Enhanced gene transfection
efficiency in CD13-positive vascular endothelial cells with targeted poly(lactic
acid)–poly(ethylene glycol) nanoparticles through caveolae-mediated endocy-
tosis. Journal of Controlled Release, 151, 162–175.
Maruyama, K. (2002). PEG-immunoliposome. Bioscience Reports, 22(2), 251–266.
Miwa, A., Ishibe, A., Nakano, M., Yamahira, T., Itai, S., Jinno, S., et al. (1998). Develop-
ment of novel chitosan derivatives as micellar carriers of taxol. Pharmaceutical
Research, 15, 1844–1850.
Mo, R., Jin, X., Li, N., Ju, C., Sun, M., Zhang, C., et al. (2011). The mechanism of enhance-
ment on oral absorption of paclitaxel by N-octyl-O-sulfate chitosan micelles.
Biomaterials, 32, 4609–4620.
Mo, R., Xiao, Y., Sun, M., Zhang, C., & Ping, Q. (2011). Enhancing effect of N-octyl-O-
sulfate chitosan on etoposide absorption. International Journal of Pharmaceutics,
409, 38–45.
Moghimi, S. M., Hunter, A. C., & Murray, J. C. (2001). Long-circulating and target-
specific nanoparticles: Theory to practice. Pharmacological Reviews, 53, 283–318.
Monier, M., Wei, Y., Sarhan, A. A., & Ayad, D. M. (2010). Synthesis and characteriza-
tion of photo-crosslinkable hydrogel membranes based on modified chitosan.
Polymer, 51, 1002–1009.
Nakagawa, O., Ming, X., Huang, L., & Juliano, R. L. (2010). Targeted intracellular deliv-
ery of antisense oligonucleotides via conjugation with small-molecule ligands.
Journal of the American Chemical Society, 132, 8848–8849.
Nasongkla, N., Shuai, X., Ai, H., Weinberg, B., Pink, J., Boothman, D. A., et al. (2004).
cRGD-functionalized polymer micelles for targeted doxorubicin delivery. Ange-
wandte Chemie International Edition, 43, 6323–6327.
Acknowledgements
Ngawhirunpat, T., Wonglertnirant, N., Opanasopit, P., Ruktanonchai, U., Yoksan, R.,
Wasanasuk, K., et al. (2009). Incorporation methods for cholic acid chitosan-g-
mPEG self-assembly micellar system containing camptothecin. Colloids Surfaces
B: Biointerfaces, 74, 253–259.
This study is financially supported by Ph.D. Programs Founda-
tion of Ministry of Education of China, 20090096110005 and 111
Project from the Ministry of Education of China the State Adminis-
tration of Foreign Expert Affairs of China (No. 111-2-07).
Nishiyama, N., Morimoto, Y., Jang, W. D.,
& Kataoka, K. (2009). Design and
development of dendrimer photosensitizer-incorporated polymeric micelles
for enhanced photodynamic therapy. Advanced Drug Delivery Reviews, 61,
327–338.
Rekha, M. R., & Sharma, C. P. (2009). Synthesis and evaluation of lauryl succinyl chi-
tosan particles towards oral insulin delivery and absorption. Journal of Controlled
Release, 135(2), 144–151.
Appendix A. Supplementary data
Rowinsky, E. K., Eisenhauer, E. A., Chaudhry, V., Arbuck, S. G., & Donehower, R. C.
(1993). Clinical toxicities encountered with Paclitaxel (Taxol). Seminar in Oncol-
ogy, 20, 1–15.
Supplementary data associated with this article can be
Saboktakin, M. R.,
& Tabatabaie, R. (2010). Synthesis and characterization of
superparamagnetic chitosan-dextran sulfate hydrogels as nano carriers for
colon-specific drug delivery. Carbohydrate Polymers, 81, 372–376.
Son, S., Singha, K., & Kim, W. J. (2010). Bioreducible BPEI-SS-PEG-cNGR polymer as
a tumor targeted nonviral gene carrier. Biomaterials, 31, 6344–6354.
Szebeni, J., Muggia, F. M., & Alving, C. R. (1998). Complement activation by cremophor
EL as a possible contributor to hypersensitivity to paclitaxel: An in vitro study.
Journal of the National Cancer Institute, 90, 300–306.
Tan, Y. L., & Liu, C. G. (2009). Self-aggregated nanoparticles from linoleic acid mod-
ified carboxymethyl chitosan: Synthesis, characterization and application in
vitro. Colloids Surfaces B: Biointerfaces, 69, 178–182.
Tishler, R. B., Geard, C. R., Hall, E. J., & Schiff, P. B. (1992). Taxol sensitizes human
astrocytoma cells to radiation. Cancer Research, 52, 3495–3497.
Torchilin, V. P., Lukyanov, A. N., Gao, Z., & Papahadjopoulos-Sternberg, B. (2003).
Immunomicelles: Targeted pharmaceutical carriers for poorly soluble drugs.
Proceedings of the National Academy of Sciences of the United States of America,
100, 6039–6044.
Trubetskoy, V. S. (1999). Polymeric micelles as carriers of diagnostic agents.
Advanced Drug Delivery Reviews, 37, 81–88.
Wang, Y. S., Jiang, Q., Li, R. S., Liu, L. L., Zhang, Q. Q., Wang, Y. M., et al. (2008). Self-
assembled nanoparticles of cholesterol-modified O-carboxymethyl chitosan as
a novel carrier for paclitaxel. Nanotechnology, 19, 145101.
Wang, H., Zhao, P., Liang, X., Gong, X., Song, T., Niu, R., et al. (2010). Folate-PEG
coated cationic modified chitosan—Cholesterol liposomes for tumor-targeted
drug delivery. Biomaterials, 31, 4129–4138.
Wang, Z., Tiruppathi, C., Cho, J., Minshall, R. D., & Malik, A. B. (2011). Delivery of
nanoparticle-complexed drugs across the vascular endothelial barrier via cave-
olae. IUBMB Life, 63(8), 659–667.
References
Amidi, M., & Hennink, W. E. (2010). Chitosan-based formulations of drugs, imaging
agents and biotherapeutics. Advanced Drug Delivery Reviews, 62, 1–2.
Backer, M. V., Gaynutdinov, T. I., Patel, V., Bandyopadhyaya, A. K., Thirumamagal, B. T.,
Tjarks, W., et al. (2005). Vascular endothelial growth factor selectively targets
boronated dendrimers to tumor vasculature. Molecular Cancer Therapeutics, 4,
1423–1429.
Carney, D. N. (1996). Chemotherapy in the management of patients with inoperable
non-small cell lung cancer. Seminars in Oncology, 23, 71–75.
Chen, X. L., Ding, S., Qu, G. W., & Zhang, C. (2008). Synthesis of novel chitosan
derivatives for micellar solubilization of Cyclosporine A. Journal of Bioactive and
Compatible Polymers, 23, 563–578.
Felt, O., Buri, P., & Gurny, R. (1998). Chitosan: A unique polysaccharide for drug
delivery. Drug Development and Industrial Pharmacy, 24, 979–993.
Goldstein, J. L., Anderson, R. G., & Brown, M. S. (1979). Coated pits, coated vesicles
and receptor-mediated endocytosis. Nature, 279, 679–685.
Huo, M., Zou, A., Yao, C., Zhang, Y., Zhou, J., Wang, J., et al. (2012).
Somatostatin receptor-mediated tumor-targeting drug delivery using
octreotide-PEG-deoxycholic acid conjugate-modified N-deoxycholic acid-O.
N-hydroxyethylation chitosan micelles. Biomaterials, 33(27), 6393–6407.
Kano, M. R., Bae, Y., Iwata, C., Morishita, Y., Yashiro, M., Oka, M., et al. (2007).
Improvement of cancer-targeting therapy, using nanocarriers for intractable
solid tumors by inhibition of TGF-beta signaling. Proceedings of the National
Academy of Sciences of the United States of America, 104, 3460–3465.
Kim, J. H., Kim, Y. S., Park, K., Lee, S., Nam, H. Y., Min, K. H., et al. (2008). Antitumor
efficacy of cisplatin-loaded glycol chitosan nanoparticles in tumor-bearing mice.
Journal of Controlled Release, 127, 41–49.
Lee, K. Y., Kim, J. H., Kwon, I. C., & Jeong, S. Y. (2000). Self-aggregates of deoxycholic
acid-modified chitosan as a novel carrier of adriamycin. Colloid and Polymer
Science, 278, 1216–1219.
Leong, K. W., Mao, H. Q., Truong-Le, V. L., Roy, K., Walsh, S. M., & August, J. T. (1998).
DNA-polycation nanospheres as non-viral gene delivery vehicles. Journal of Con-
trolled Release, 53, 183–193.
Wu, D. Q., Lu, B., Chang, C., Chen, C. S., Wang, T., & Zhang, Y. Y. (2009). Galactosylated
fluorescent labeled micelles as a liver targeting drug carrier. Biomaterials, 30,
1363–1371.
Yao, Z., Zhang, C., Ping, Q., & Yu, L. (2007). A series of novel chitosan derivatives: Syn-
thesis, characterization and micellar solubilization of paclitaxel. Carbohydrate
Polymers, 68, 781–792.
Ye, Y. Q., Yang, F. L., Hu, F. Q., Du, Y. Z., Yuan, H., & Yu, H. Y. (2008). Core-modified
chitosan-based polymeric micelles for controlled release of doxorubicin. Inter-
national Journal of Pharmaceutics, 352, 294–301.