Synthesis of PEGylated carboxymethyl chitosan-rhein conjugate and preparation of paclitaxel-loaded polymeric micelles

WANG Xiaying; QIU Liangzhen; LI Qingzhuo; XU Wei; WANG Xiaoying

doi:10.11665/j.issn.1000-5048.20180512

Journal of China Pharmaceutical University > 2018 > 49(5): 596-602. > DOI: 10.11665/j.issn.1000-5048.20180512

WANG Xiaying, QIU Liangzhen, LI Qingzhuo, XU Wei, WANG Xiaoying. Synthesis of PEGylated carboxymethyl chitosan-rhein conjugate and preparation of paclitaxel-loaded polymeric micelles[J]. Journal of China Pharmaceutical University, 2018, 49(5): 596-602. DOI: 10.11665/j.issn.1000-5048.20180512

Citation:

PDF (2192 KB)

Synthesis of PEGylated carboxymethyl chitosan-rhein conjugate and preparation of paclitaxel-loaded polymeric micelles

More Information

Graphical Abstract

Abstract

Abstract

Paclitaxel(PTX), an effective anti-tumor drugs, is water-insoluble. And Cremophor as a solubilizer in its commercial formulation, Taxol^®, often causes side-effects which limit its antitumor effect. We designed and synthesized PEGylated carboxymethyl chitosan-rhein(CRmP)conjugate, and further prepared PTX-loaded CRmP polymeric micelles(PTX/CRmP). CRmP conjugate was characterized by fourier transform infrared spectrum(FT-IR)and nuclear magnetic resonance spectroscopy(¹H NMR). The particle size and surface morphology of PTX/CRmP were characterized by dynamic laser particle size analyzer(DLS)and atomic force microscope(AFM), respectively. The cytotoxicity of CRmP conjugate and PTX/CRmP against MCF-7 cells were evaluated by MTT assay. The results showed that CRmP conjugates displayed very low cytotoxicity and that PTX/CRmP exhibited better in vitro anti-tumor activity than Taxol^® at the same drug concentration after a long-term administration.
- paclitaxel,
- carboxymethyl chitosan,
- PEG,
- rhein,
- polymer micelles,
- anti-tumor,
- characterization

FullText(HTML)

References (20)

References

[1]	Liu J,Li H,Chen D,et al.In vivo evaluation of novel chitosan graft polymeric micelles for delivery of paclitaxel[J].Drug Deliv,2011,18(3):181-189.
[2]	Wang Y,Liang X,Tong R,et al.Gambogic acid-loaded polymeric micelles for improved therapeutic effect in breast cancer[J].J Biomed Nanotechnol,2018,14(10):1695-1704.
[3]	Chen G,Wang Y,Xie R,et al.A review on core-shell structured unimolecular nanoparticles for biomedical applications[J].Adv Drug Deliv Rev,2018,130:58-72.
[4]	Cabral H,Kataoka K.Progress of drug-loaded polymeric micelles into clinical studies[J].J Control Release,2014,190:465-476.
[5]	Sabra S,Abdelmoneem M,Abdelwakil M,et al.Self-assembled nanocarriers based on amphiphilic natural polymers for anti-cancer drug delivery applications[J].Curr Pharm Des,2017,23(35):5213-5229.
[6]	Jimtaisong A,Saewan N.Utilization of carboxymethyl chitosan in cosmetics[J].Int J Cosmetic Sci,2014,36(1):12-21.
[7]	Sahu SK,Maiti S,Pramanik A,et al.Controlling the thickness of polymeric shell on magnetic nanoparticles loaded with doxorubicin for targeted delivery and MRI contrast agent[J].Carbohyd Polym,2012,87(4):2593-2604.
[8]	Wang DD,A LN,Mao Y,et al.Rhein induces apoptosis in L-02 cells via reactive oxygen species-independent endoplasmic reticulum stress pathway [J].J China Pharm Univ(中国药科大学学报),2016,47(2):215-221.
[9]	Du Q,Bian XL,Xu XL,et al.Role of mitochondrial permeability transition in human hepatocellular carcinoma Hep-G2 cell death induced by rhein[J].Fitoterapia,2013,91:68-73.
[10]	Lin YJ,Zhen YZ,Shang BY,et al.Rhein lysinate suppresses the growth of tumor cells and increases the anti-tumor activity of Taxol in mice[J].Am J Chin Med,2009,37(5):923-931.
[11]	Abuchowski A,McCoy JR,Palczuk NC,et al.Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase[J].J Biol Chem,1977,252(11):3582-3586.
[12]	Ginn C,Khalili H,Lever R,et al.PEGylation and its impact on the design of new protein-based medicines[J].Future Med Chem,2014,6(16):1829-1846.
[13]	Hoffman AS.The early days of PEG and PEGylation(1970s-1990s)[J].Acta Biomater,2016,40:1-5.
[14]	Vllasaliu D, Fowler R, Stolnik S. PEGylated nanomedicines:recent progress and remaining concerns[J].Expert Opin Drug Del,2013,11(1):139-154.
[15]	Liu Y,Zhou J,Wang W.Advances in PEGylated targeted nano-preparation[J].J China Pharm Univ(中国药科大学学报),2017,48(3):268-275.
[16]	Kolate A,Baradia D,Patil S,et al.PEG - a versatile conjugating ligand for drugs and drug delivery systems[J].J Control Release,2014,192:67-81.
[17]	Suk JS,Xu Q,Kim N,et al.PEGylation as a strategy for improving nanoparticle-based drug and gene delivery[J].Adv Drug Deliv Rev,2016,99(Pt A):28-51.
[18]	Shi J,Kantoff PW,Wooster R,et al.Cancer nanomedicine:progress,challenges and opportunities[J].Nat Rev Cancer,2017,17(1):20-37.
[19]	Danhier F,Danhier P,De Saedeleer CJ,et al.Paclitaxel-loaded micelles enhance transvascular permeability and retention of nanomedicines in tumors[J].Int J Pharm,2015,479(2):399-407.
[20]	Cabral H,Kataoka K.Progress of drug-loaded polymeric micelles into clinical studies[J].J Control Release,2014,190:465-476.

Cited By

Get Citation

PDF

XML

Article views (911) PDF downloads (1006)

Turn off MathJax

Article Contents

Abstract

References

Synthesis of PEGylated carboxymethyl chitosan-rhein conjugate and preparation of paclitaxel-loaded polymeric micelles

Abstract

References

Catalog

Export File

Citation

Format

Content