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Effect of methotrexate conjugated PAMAM dendrimers on the viability of MES-SA uterine cancer cells.

Khatri S, Das NG, Das SK - J Pharm Bioallied Sci (2014)

Bottom Line: The amide-bonded PAMAM dendrimer-MTX conjugates were prepared by conjugation between the amine-terminated G5 dendrimer and the carboxylic groups of the MTX using a dicyclohexylcarbodiimide coupling reaction.The UV and (1)H NMR study confirmed the formation of covalent bonds between the drug and the dendrimer.The cell viability study indicated that the nanoconjugates had significantly improved cell killing compared to the free MTX.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Butler University, Indianapolis, IN 46208, USA.

ABSTRACT
The aim of this work was to synthesize methotrexate (MTX)-polyamidoamine (PAMAM) dendritic nanoconjugates and to study their effect on cell viability in uterine sarcoma cells. The amide-bonded PAMAM dendrimer-MTX conjugates were prepared by conjugation between the amine-terminated G5 dendrimer and the carboxylic groups of the MTX using a dicyclohexylcarbodiimide coupling reaction. The formation of conjugates was evaluated by ultraviolet (UV) and (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy studies. The cell survival of MES-SA cells, a uterine sarcoma cell line, was evaluated in the presence of the dendrimer-MTX nanoconjugate, using appropriate controls. The UV and (1)H NMR study confirmed the formation of covalent bonds between the drug and the dendrimer. The cell viability study indicated that the nanoconjugates had significantly improved cell killing compared to the free MTX.

No MeSH data available.


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Scheme of synthesis of polyamidoamine-G5-NH2-methotrexate conjugate
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Figure 1: Scheme of synthesis of polyamidoamine-G5-NH2-methotrexate conjugate

Mentions: All lab ware was cleaned carefully to avoid the introduction of foreign particulates in the formulations and formulation processing involving potentially harmful organic solvents were limited to a certified chemical hood. MTX (1 mg), PAMAM-G5-NH2 dendrimer (10 μl, 10% w/v in methanol, 0.791 g/ml at 25°C) were dissolved in 1 ml DMSO followed by addition of DCC (5 mg). The mixture was stirred continuously for three days at room temperature in complete darkness. The MTX-dendrimer conjugate is formed by a reaction between –NH2 end groups of dendrimer and the –COOH group of MTX (especially the γ-COOH group of MTX) [Figure 1]. The reaction mixture was purified by dialyzing against DMSO for 24 hour to remove free MTX and DCC. Although the size distribution of the dendrimer-MTX conjugate was expected to be in the nanometer range, the product was filtered through a sterile membrane filter to ensure preparatory aseptic processing for cell culture studies, as well as the removal of any residual particulate dicyclohexylurea (DCU) that formed as a byproduct and may have precipitated during the conjugation process. An earlier report indicated the conjugation ratio of MTX to hydrazide-terminated dendrimers was 4.7.[26]


Effect of methotrexate conjugated PAMAM dendrimers on the viability of MES-SA uterine cancer cells.

Khatri S, Das NG, Das SK - J Pharm Bioallied Sci (2014)

Scheme of synthesis of polyamidoamine-G5-NH2-methotrexate conjugate
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231390&req=5

Figure 1: Scheme of synthesis of polyamidoamine-G5-NH2-methotrexate conjugate
Mentions: All lab ware was cleaned carefully to avoid the introduction of foreign particulates in the formulations and formulation processing involving potentially harmful organic solvents were limited to a certified chemical hood. MTX (1 mg), PAMAM-G5-NH2 dendrimer (10 μl, 10% w/v in methanol, 0.791 g/ml at 25°C) were dissolved in 1 ml DMSO followed by addition of DCC (5 mg). The mixture was stirred continuously for three days at room temperature in complete darkness. The MTX-dendrimer conjugate is formed by a reaction between –NH2 end groups of dendrimer and the –COOH group of MTX (especially the γ-COOH group of MTX) [Figure 1]. The reaction mixture was purified by dialyzing against DMSO for 24 hour to remove free MTX and DCC. Although the size distribution of the dendrimer-MTX conjugate was expected to be in the nanometer range, the product was filtered through a sterile membrane filter to ensure preparatory aseptic processing for cell culture studies, as well as the removal of any residual particulate dicyclohexylurea (DCU) that formed as a byproduct and may have precipitated during the conjugation process. An earlier report indicated the conjugation ratio of MTX to hydrazide-terminated dendrimers was 4.7.[26]

Bottom Line: The amide-bonded PAMAM dendrimer-MTX conjugates were prepared by conjugation between the amine-terminated G5 dendrimer and the carboxylic groups of the MTX using a dicyclohexylcarbodiimide coupling reaction.The UV and (1)H NMR study confirmed the formation of covalent bonds between the drug and the dendrimer.The cell viability study indicated that the nanoconjugates had significantly improved cell killing compared to the free MTX.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Butler University, Indianapolis, IN 46208, USA.

ABSTRACT
The aim of this work was to synthesize methotrexate (MTX)-polyamidoamine (PAMAM) dendritic nanoconjugates and to study their effect on cell viability in uterine sarcoma cells. The amide-bonded PAMAM dendrimer-MTX conjugates were prepared by conjugation between the amine-terminated G5 dendrimer and the carboxylic groups of the MTX using a dicyclohexylcarbodiimide coupling reaction. The formation of conjugates was evaluated by ultraviolet (UV) and (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy studies. The cell survival of MES-SA cells, a uterine sarcoma cell line, was evaluated in the presence of the dendrimer-MTX nanoconjugate, using appropriate controls. The UV and (1)H NMR study confirmed the formation of covalent bonds between the drug and the dendrimer. The cell viability study indicated that the nanoconjugates had significantly improved cell killing compared to the free MTX.

No MeSH data available.


Related in: MedlinePlus