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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996 EISSN: 1596-5996
Vol. 16, No. 4, 2017, pp. 737-742
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Bioline Code: pr17094
Full paper language: English
Document type: Research Article
Document available free of charge
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Tropical Journal of Pharmaceutical Research, Vol. 16, No. 4, 2017, pp. 737-742
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Preparation and evaluation of peptide-dendrimer-paclitaxel conjugates for treatment of heterogeneous stage 1 non-small cell lung cancer in 293T and L132 cell lines
Zhang, Wei-wei; Wang, Yan-chun; Kan, Xiang-ming; Wang, Xue-mei & Geng, Dong-mei
Abstract
Purpose: To develop peptide-dendrimer-paclitaxel conjugates for the treatment of heterogeneous stage
1 non small cell lung cancer (NSCLC) in 293T and L132cell line.
Method: Dendrimer-paclitaxel conjugates (PAMAM-PTX) were prepared by NHS method and the
conjugates were used for the synthesis of peptide-dendrimer-paclitaxel conjugates (GE-PAMAM-PTX).
The particle sizes of PAMAM-PTX and GE-PAMAM-PTX were measured. Entrapment efficiency of PTX
in PAMAM-PTX was measured while GE-PAMAM-PTX. PTX release from PAMAM-PTX and GEPAMAM-PTX was determined using a dialysis bag in pH 7.4 phosphate buffer. The cytotoxicity of
PAMAM-PTX, GE-PAMAM-PTX, PAMAM and PTX was evaluated by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay using 293T cell lines. In vitro cellular uptake assay of
PAMAM-PTX and GE-PAMAM-PTX and PTX at concentrations ranging from 0.01 to 0.5μM for 8 h was
carried out in NSCLC cell lines 293T and L132.
Results: More than 95 % entrapment efficiency of GE-PAMAM-PTX was observed with loading
efficiency of 25 %. GE-PAMAM-PTX conjugates showed sustained release of PTX (~85 %) towards the
end of 50 h. GE-PAMAM-PTX conjugates were more cytotoxic than pure PTX and PAMAM-PTX
conjugates. The remarkable uptake of GE-PAMAM-PTX appear to be due to receptor-mediated
endocytosis in the cell lines. The presence of ligand (GE) on PAMAM-PTX surface enabled the complex
to bind to the over-expressed receptors on the cell lines.
Conclusion: GE-PAMAM-PTX can facilitate targeting of paclitaxel to lung cancer cell lines and tumors
and facilitate release of the drugs in a sustained manner to improve the therapeutic efficacy of PTX.
Keywords
Paclitaxel, Lung cancer, Non-small cell lung cancer, Dendrimer, Peptide, PAMAM
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