Wei-wei Zhang1,
Yan-chun Wang1,
Xiang-ming Kan1,
Xue-mei Wang2,
Dong-mei Geng1 
For correspondence:- Dong-mei Geng Email: gengdongmei328@hotmail.com
Received: 2 November 2016 Accepted: 9 March 2017 Published: 29 April 2017
Citation: Zhang W, Wang Y, Kan X, Wang X, Geng D. 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. Trop J Pharm Res 2017; 16(4):737-742 doi: 10.4314/tjpr.v16i4.1
© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
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.
Methods: 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 GE-PAMAM-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.
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