Physicochemical properties and biocompatibility of a polymer-paclitaxel conjugate for cancer treatment.

Abstract

BACKGROUND:

Poly(L-γ-glutamylglutamine) paclitaxel (PGG-PTX) conjugate is a non-diblock polymeric drug nanoparticle intended to improve the therapeutic index of paclitaxel. The purpose of the present study was to elucidate further the physicochemical properties of PGG-PTX in order to proceed with its clinical development.

METHODS AND RESULTS:

PGG-PTX was designed by integration of a hydrophobic paclitaxel conjugate through an added hydrophilic glutamic acid onto poly(L-glutamic acid). The addition of a flexible glutamic linker between PGA and paclitaxel resulted in spontaneous self-assembly of a PGG-PTX conjugate into nanoparticles. The PGG-PTX conjugate was stable as a lyophilized solid form. An in vitro viability experiment showed that PGG-PTX was effective after a longer incubation period, the same trend as Taxol. In vitro studies using NCI-H460 and B16F0 cancer cells demonstrated significantly high cellular uptake after 30 minutes of incubation. The in vivo biocompatibility of PGG-PTX conjugate was evaluated in the NCI-H460 tumor model, the assessment of tissue seemed to be normal after 21 days of treatment.

CONCLUSION:

These results are encouraging for further development of non-block polymeric paclitaxel nanoparticles for treatment of cancer.

• Authors: Danbo Yang, Sang Van, Jian Liu, Jing Wang, Xinguo Jiang, Yiting Wang, Lei Yu
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 6 Pg. 2557-66 ( 2011) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 22072890 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Biocompatible Materials
• Drug Carriers
• Proteins
• poly(gamma-glutamylglutamine)paclitaxel
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacokinetics, pharmacology)
• Biocompatible Materials (chemistry, pharmacokinetics, pharmacology)
• Caco-2 Cells
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Carriers (chemistry, pharmacokinetics, pharmacology)
• Drug Stability
• Erythrocyte Aggregation (drug effects)
• Female
• Hemolysis (drug effects)
• Humans
• Male
• Mice
• Mice, Nude
• Microscopy, Electron, Transmission
• Microscopy, Fluorescence
• Nanoparticles (administration & dosage, chemistry)
• Paclitaxel (analogs & derivatives, chemistry, pharmacokinetics, pharmacology)
• Proteins (chemistry, pharmacokinetics, pharmacology)
• Random Allocation
• Thermogravimetry
• Xenograft Model Antitumor Assays