Association Behavior of Biotinylated and Non-Biotinylated Poly(ethylene oxide)-b-poly(2-(diethylamino)ethyl methacrylate)

Abstract

-Biotinylated and non-biotinylated copolymers of ethylene oxide (EO) and 2-(diethylamino)ethyl methacrylate (DEAEMA) were synthesized by the atom transfer radical polymerization technique (ATRPrespectively. The aggregation behavior of these polymers in aqueous solutions at different pHs and ionic strengths was studied using a combination of potentiometric titration, dynamic light scattering (DLS), static light scattering (SLS), and transmission electron microscopy (TEM). Both PEO-b-PDEAEMA and biotin-PEO-b-PDEAEMA diblock copolymers form micelles at high pH with hydrodynamic radii (R h ) of about 19 and 23 nm, respectively. At low pH, the copolymers are dispersed as unimers in solution with R h of about 6-7 nm. However, at a physiological salt concentration (c s ) of about 0.16M NaCl and a pH of 7-8, the copolymers form large loosely packed Guassian chains, which were not present at the low c s of 0.001M NaCl. The critical micelle concentrations (CMC) and the cytotoxicity of the copolymers were investigated to determine a suitable polymer concentration range for future biological applications. Both PEO-b-PDEAEMA and biotin-PEO-b-PDEAEMA diblock copolymers possess identical CMC values of about 0.0023 mg/g, while the cytotoxicity test indicated that the copolymers are not toxic up to 0.05mg/g (> 83% cell survival at this concentration).

Biotinylated thermoresponsive micelle self-assembled from double-hydrophilic block copolymer for drug delivery and tumor target

“…Biotin-poly(ethylene glycol)-block-poly(N-isopropylacrylamide-co-N-hydroxymethyl acrylamide) (biotin-PEG-b-P(NIPAAm-co-HMAAm)) was designed and prepared. PEG segment was introduced as a highly hydrophilic block due to its good biocompatibility and the ability to stabilize the micelles as well as protect them from being cleared up by the reticuloendothelial system (RES) [9]. The biotin part was utilized for the pretargeting in tumor chemotherapy [4], and the conjugation of biotin moiety with the copolymer was investigated by a unique capillary electrophoresis immunoassay (CEIA) method based on enhanced chemiluminescence (CL) detection.…”

pH‐Responsive Flower‐Type Micelles Formed by a Biotinylated Poly(2‐vinylpyridine)‐block‐poly(ethylene oxide)‐block‐poly(ε‐caprolactone) Triblock Copolymer

“…It is also known that only a few ligands per micelle are required for cell targeting to be effective. [25,48,49] After quaternization, the reaction medium was dialyzed against water in order to eliminate unreacted biotin-bromide. Although 1 H NMR spectroscopy was not sensitive enough to detect the low amounts of biotin, the attachment of this ligand to the triblock copolymer was qualitatively confirmed by thin-layer chromatography and the characteristic pink colouring of the copolymer spot upon reaction with p-(dimethylamino) cinnamaldehyde.…”

Self-assembling Pluronic®-modified polycations in gene delivery

“…The colloidal stability of polycation-DNA complexes, which tend to aggregate in aqueous solutions, especially under physiological conditions, due to the charge neutralization and thus lack of electrostatic repulsion between the particle aggregates, can be enhanced via the covalent attachment and non-covalent binding of hydrophilic polymers onto polycations, resulting in steric stabilization of the complexes [12-15 • ]. Among such hydrophilic polymers used for steric stabilization of polycations and their complexes with DNA, poly(ethylene oxide) (PEO) is the most prominent [8,9,12,16], although multivalent copolymers of N-(2-hydroxypropyl)methacrylamide (PHPMA) have also been utilized [17]. Coupling of PEO to polycations results in hydrophilic shielding ("stealth" effect) similar to PEGylated liposomes [12,17-19 •• ,20].…”

“…The modification of polycations may reduce the potential of non-specific interactions, such as opsonization or deposition due to cationic surface charges. Modification with PEO afforded improved colloidal properties of the complexes of PEO-modified polycations and DNA, such as a neutral zeta potential, low cytotoxicity, and little or no tendency for aggregation in vitro [16].…”