Preparation and Biophysical Characterization of Pluronic F127-Dendrimer Conjugate as a Delivery Agent of Antisense Oligonucleotides

Abstract

A series of pluronic F127 conjugated PAMAM dendrimer generation 5 were prepared to evaluate the potential use of dendrimer-pluronic conjugates as a delivery agent of antisense oligonucleotides. The structural features of the conjugates were identified by FT-IR and 1H-NMR spectra. The prepared dendrimer generation 5-pluronic F127 conjugates showed particle size in the range of 50 to 130 nm with reduced zeta potential. The electrophoretic property of conjugates was further confirmed by capillary zone electrophoresis (CZE), demonstrating the decrease in electrophoretic mobility of conjugates as the number of pluronic F127 on surface of dendrimer increases. The number of free amino groups on a pluronic F127 conjugated dendrimer was quantitatively determined by fluorescamine assay, measuring the fluorescence intensity of amino groups reactive to fluorescamine on dendrimer generation 5-pluronic F127 conjugates. In MTT assay, dendrimer G5-pluronic F127 conjugates were safe on gingival fibroblast cells and acute toxicity was reduced as the mole ratio of dendrimer to pluronic increased. Complex formation of dendrimer G5-pluronic F127 conjugates with oligonucleotides was dose dependent.

Protective effect of PEGylation against poly(amidoamine) dendrimer‐induced hemolysis of human red blood cells

“…The presence of these terminal groups in dendrimers facilitates multiple simultaneous interactions with other molecules 2. As one of the most popular dendrimers, generation 5 (G5) PAMAM dendrimers with 128 amine terminals have been successfully used in field of biomedicine such as drug delivery, gene transfection, imaging, and anti‐infection 3–15…”

“…2 As one of the most popular dendrimers, generation 5 (G5) PAMAM dendrimers with 128 amine terminals have been successfully used in field of biomedicine such as drug delivery, gene transfection, imaging, and anti-infection. [3][4][5][6][7][8][9][10][11][12][13][14][15] Despite the extensive interest in pharmaceutical applications of dendrimers, there are conflicting reports regarding their biological safety. 16,17 It has been reported that G2-G4 PAMAM dendrimers would cause concentration-and generation-dependent damage to red blood cells (RBCs).…”

Poloxamer 188 enhances apoptosis in a human leukemia cell line

“…These drugs also affect proteins or nucleic acids that are present in normal as well as malignant tissues. Targeted therapy (23,24) using pluronic F68 as a carrier may be more effective than current treatments and less harmful to normal cells. Pluronic F68 appears to possess unique drug-targeted cancer cell interactions in the K5262 cell line.…”

Highly lipophilic pluronics-conjugated polyamidoamine dendrimer nanocarriers as potential delivery system for hydrophobic drugs

“…Among of the copolymers, pluronic F127 and its derivatives have been the most widely studied materials for delivering several kinds of drugs and proven its loading efficiency [2,3,29,31,32]. Pluronic F127 was also used to functionalize PAMAM dendrimers.…”