Paclitaxel-loaded poly(gamma-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system against cultured HepG2 cells.
The study was to develop paclitaxel-loaded formulations using a novel type of self-assembled nanoparticles that was composed of block copolymers synthesized from poly(gamma-glutamic acid) and poly(lactide) via a simple coupling reaction. The nanoparticles (the NPs) were prepared with various feed weight ratios of paclitaxel to block copolymer (the P/BC ratio). The morphology of all prepared nanoparticles was spherical and the surfaces were smooth. Increasing the P/BC ratio significantly increased the drug loading content of the prepared nanoparticles, but remarkably reduced the drug loading efficiency. The release rate of paclitaxel from the NPs decreased significantly as the P/BC ratio increased. For the potential of targeting liver cancer cells, galactosamine was further conjugated on the prepared nanoparticles (the Gal-NPs) as a targeting moiety. It was found that the activity in inhibiting the growth of HepG2 cells (a liver cancer cell line) by the Gal-NPs was comparable to that of a clinically available paclitaxel formulation, while the NPs displayed a significantly less activity. This may be attributed to the fact that the Gal-NPs had a specific interaction with HepG2 cells via ligand-receptor recognition. Cells treated with distinct paclitaxel formulations resulted in arrest in the G2/M phase. The arrest of cells in the G2/M phase was highly suggestive of interference by paclitaxel with spindle formation and was consistent with the morphological findings presented herein. In conclusion, the active targeting nature of the Gal-NPs prepared in the study may be used as a potential drug delivery system for the targeted delivery to liver cancers.
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Hsiang-Fa
HF
Liang
Sung-Ching
SC
Chen
Mei-Chin
MC
Chen
Po-Wei
PW
Lee
Chiung-Tong
CT
Chen
Hsing-Wen
HW
Sung
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005688:Galactosamine / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry; D017239:Paclitaxel / Q000031:analogs & derivatives; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D011099:Polyglutamic Acid / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use / Q000031:analogs & derivatives; D043823:Taxoids / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D011091:Polyesters; D043823:Taxoids; D011099:Polyglutamic Acid; C033616:poly(lactide); D005688:Galactosamine; D017239:Paclitaxel; C509139:paclitaxel poliglumex