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
Highlights
Lung cancer is known as pulmonary carcinoma
The particle size of PAMAM-PTX and GEPAMAM-PTX was 110 and 112.5 nm, respectively. Entrapment efficiency of both PAMAM-PTX and GE-PAMAM-PTX were more than 95 % with effective loading efficiency of 25 %.Release of PTX from PAMAM-PTX and GE-PAMAM-PTX was done in phosphate buffered saline
The results indicate that addition of GE11 peptide on PAMAM-PTX conjugate did not alter the particle size distribution characteristics
Summary
Lung cancer is known as pulmonary carcinoma. Lung cancer is characterized by the uncontrolled growth of cells in the tissues of lung. It has been found that about 85 – 90 % of lung cancer patients are histologically diagnosed with NSCLC [2,3]. Chemotherapy, surgery, radiation therapy or combinations of these are the best treatment options for patients suffering from NSCLC. Among these available treatment options chemotherapy and radiation therapy has very little success rate for the treatment of NSCLC [4]. Presently available treatment options have limited tumor killing potential and suffer from serious systemic toxicity. The major problem associated with current chemotherapy is nonspecific tumor targeting that kills normal cells as well severe side effects in patients with NSCLC [5]
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