Synthesis and characterization of dexamethasone‐conjugated linear polyethylenimine as a gene carrier

Abstract

Linear polyethylenimine (25 kDa, LPEI25k) has been shown to be an effective non-viral gene carrier with higher transfection and lower toxicity than branched polyethylenimine (BPEI) of comparable molecular weight. In this study, dexamethasone was conjugated to LPEI25k to improve the efficiency of gene delivery. Dexamethasone is a synthetic glucocorticoid receptor ligand. Dexamethasone-conjugated LPEI25k (LPEI-Dexa) was evaluated as a gene carrier in various cells. Gel retardation assays showed that LPEI-Dexa completely retarded plasmid DNA (pDNA) at a 0.75:1 weight ratio (LPEI/pDNA). LPEI-Dexa had the highest transfection efficiency at a 2:1 weight ratio (LPEI-Dexa/DNA). At this ratio, the size of the LPEI-Dexa/pDNA complex was approximately 125 nm and the zeta potential was 35 mV. LPEI-Dexa had higher transfection efficiency than LPEI and Lipofectamine 2000. In addition, the cytotoxicity of LPEI-Dexa was much lower than that of BPEI (25 kDa, BPEI25k). In conclusion, LPEI-Dexa has a high transfection efficiency and low toxicity and can therefore be used for non-viral gene delivery.

Cholic acid modified 2 kDa polyethylenimine as efficient transfection agent

“…Similarly, Dex-polymer complexes (PEI25 and PEI2) were reported to have increased pDNA binding as compared to native PEI. 7,8 Enhanced hydrophobic associations in the case of Dex might explain this difference from our results. 12 Therefore, it could be concluded that whether a lipophilic substituent enhances or impedes pDNA binding might depend on substituent's nature.…”

“…However, unlike our results, Huh et al noted that chitosan‐ChA conjugates better self‐assembled under aqueous conditions due to strong hydrophobic interactions among the ChA moieties. Similarly, Dex‐polymer complexes (PEI25 and PEI2) were reported to have increased pDNA binding as compared to native PEI . Enhanced hydrophobic associations in the case of Dex might explain this difference from our results .…”

“…Reaction conditions leading to such a difference in substitution levels were not articulated. Even with a linear PEI, ample substitutions were reported for Dex (∼23 Dex/polymer), but whether the substitution level was controlled by reaction conditions was not evident . Similarly, Gusachenko et al reported cholesterol substitution to PEI25 using a preactivated cholesteryl chloroformate, but the authors did not confirm the extent of modification even though several polymer:cholesteryl chloroformate ratios were used for synthesis.…”

“…Even with a linear PEI, ample substitutions were reported for Dex (23 Dex/polymer), but whether the substitution level was controlled by reaction conditions was not evident. 8 Similarly, Gusachenko et al 9 reported cholesterol substitution to PEI25 using a preactivated cholesteryl chloroformate, but the authors did not confirm the extent of modification even though several polymer:cholesteryl chloroformate ratios were used for synthesis. Although Bajaj et al 10 could control the extent of substitution, they used a four-step reaction to prepare PEI-cholesterol conjugates.…”

Transferrin-PEG-PE modified dexamethasone conjugated cationic lipid carrier mediated gene delivery system for tumor-targeted transfection

“…Dexamethasone (Dexa), an effective, synthetic glucocorticoid, could bind to the glucocorticoid receptor after cellular entry and translocate the complexes into the nucleus. [15][16][17][18][19][20] The results of these studies have confirmed that Dexa-conjugated vector/DNA complexes could be efficiently delivered into the nucleus with the glucocorticoid receptor, resulting in increased transgene expression.…”