Characterization of Polyion Complex Micelles Designed to Address the Challenges of Oligonucleotide Delivery

Abstract

PEG 3000-based PICMs possess good colloidal properties, intermediate stability towards dissociation and adjustable buffering capacity, making them potentially useful for the delivery of nucleic acid drugs.

Well-defined block copolymers for gene delivery to dendritic cells: Probing the effect of polycation chain-length

“…1, the PAEM block has a flexible backbone of polymethacrylate with side-chains terminated in primary amines. Polymethacrylate derivatives such as PAEM can be synthesized by controlled radical polymerization (such as ATRP) that offers a convenient and effective means to generate polymers with well-defined chain-length, composition, and molecular architecture [21, 24, 31]. Therefore, PEG- b -PAEM may serve as a model system, which not only allows one to probe mechanistically the structure-function relationship in the context of DNA vaccine delivery to DCs, but with further modification, may also emerge as practically useful DNA vaccine formulations.…”

“…A direct comparison between PAEM and polylysine in terms of DNA binding and gene transfection properties may be an interesting topic for future investigation. While polymers containing secondary and tertiary amines such as poly(dimethyl aminoethyl methacrylate) (PDAEMA) and a variety of other cationic moieties have been postulated to facilitate subcellular trafficking and DNA release [30], primary amines of PAEM maintain the maximum capacity of condensing DNA at physiological pH and can easily incorporate other types of amines through chemical transformation or copolymerization [21, 31]. …”

“…1, consists of a simple cationic block with primary amines for DNA binding and a PEG block for steric stabilization of polymer/DNA complexes. PEG- b -PAEM copolymers can be synthesized using a controlled polymerization technique, atom transfer radical polymerization (ATRP), resulting in polymer blocks of defined length that have been previously shown to influence the complexation with heparin [21] and oligonucleotides [31]. Here we report results of physico-chemical characterization of PEG- b -PAEM/DNA plasmid complexes, their interactions with DCs in vitro (including uptake, cytotoxicity, gene transfection, and phenotypic maturation), and targeted uptake by DCs in vivo , aiming to illustrate how synthetic polymers with well-defined molecular features such as polycation chain-length may have a profound influence on the delivery of cargos to DCs.…”

Polymers for Drug Delivery Systems

“…The use of a block copolymer affords modular functionality; the polycationic poly( l -lysine) segment serves to bind siRNA and provide endosomal buffering capacity (80) whereas the hydrophilic PEG segment prolongs circulation time, prevents aggregation, and reduces opsonization (65). Lysine groups of the PEG- b -PLL copolymer were reacted with 2-iminothiolane and subsequently oxidized to form disulfide cross-links.…”

The Investigation on Polyion Complex Micelles Composed of Diammonium Glycyrrhizinate/Poly(Ethylene Glycol)–Glycidyltrimethylammonium Chloride-Grafted Polyasparthydrazide

“…Generally, the charged copolymer is soluble in aqueous medium, and its chemical structure is composed of a charged segment and a neutral hydrophilic segment. The charged part of the copolymer and oppositely charged drug generate an electrostatic attraction that results in an insoluble internal core and the hydrophilic segment surrounding the core as a corona (7)(8)(9). Since PIC micelles are prepared by simply mixing the drug and polymeric solutions, this approach eliminates the need for solvents.…”