A one-step process in preparation of cationic nanoparticles with poly(lactide-co-glycolide)-containing polyethylenimine gives efficient gene delivery.

A one-step preparation of nanoparticles with poly(lactide-co-glycolide) (PLGA) pre-modified with polyethylenimine (PEI) is better in requirements for DNA delivery compared to those prepared in a two-step process (preformed PLGA nanoparticles and subsequently coated with PEI). The particles were prepared by emulsification of PLGA/ethyl acetate in an aqueous solution of PVA and PEI. DLS, AFM and SEM were used for the size characteristics.

Synthesis and evaluation of poly(hexamethylene-urethane) and PEG-poly(hexamethylene-urethane) and their cholesteryl oleyl carbonate composites for human blood biocompatibility.

Two new urethane-based acrylates (UAA and PEG-UAA) were synthesized as polymer blocks. The chemical composition of the two monomers was confirmed by IR and NMR. After cross-linking these blockers by radical polymerization, "hexamethylene PU" [poly(hexamethylene-urethane)] and "PEG-hexamethylene PU" [PEG-poly(hexa-methylene-urethane)] were obtained.

New cationic biodegradable poly(urethane-co-ester): synthesis, structural characterization, modification and gene delivery.

To improve the transfection efficiency of poly(urethane-co-ester) and the cytotoxicity of PEI25k with DNA, we synthesized a new poly(urethane-co-ester), PUE, bearing ester linkages and amino groups in the backbone and urethane linkages in the side-chain, and then prepared a binary mixture, PUE-PEI25k, using a physical blending method. The structure of PUE was confirmed by FT-IR and NMR spectra. Both poly(urethane-co-ester), PUE, and binary mixture PUE-PEI25k, readily self-assembled with plasmid DNA (pCMV-βgal) in a HEPES buffer, were characterized by dynamic light scattering.

Synthesis and characterizations of new glycidyl-based cationic poly(aminoester) and study on gene delivery.

New glycidyl-based (epoxide-based) poly(aminoester) (EPAE) containing hydroxyl and amino groups in the backbone and side chain was synthesized. EPAE self-assembled readily with the plasmid DNA(pCMV-betagal) in HEPES buffer and was characterized by dynamic light scattering, Zeta-potential, fluorescence images, and XTT cell viability assays. To evaluate the effect of molecular weight of EPAE system on transfection, EPAE polymers with three different molecular weights (EPAE22k, EPAE18k, and EPAE8k) were also prepared.

The characteristics and transfection efficiency of PEI modified by biodegradable poly(beta-amino ester).

To improve the cytotoxicity of PEI25k and the transfection efficiency of poly(beta-amino ester) with DNA, we synthesized a poly(beta-amino ester), PEDP, bearing ester linkages in the backbone and tertiary amines in the backbone and side chain and prepared a binary mixture, PEDP-PEI25k, using physical blending meyhod. Both poly(beta-amino ester) PEDP and binary mixture PEDP-PEI25k, readily self-assembled with plasmid DNA (pCMV-beta gal) in a HEPES buffer, were characterized by dynamic light scattering. The results reveal that PEDP-PEI25k was able to self-assemble plasmid DNA into PEDP-PEI25k/DNA nano-complexes small enough to enter a cell through endocytosis.

The characteristics and transfection efficiency of cationic poly (ester-co-urethane) - short chain PEI conjugates self-assembled with DNA.

To improve the transfection efficiency of polycations with DNA, we synthesized poly(ester-co-urethane)(PEU-g-PEI800) with short chain PEI800 in the side chain, and poly(ester-co-urethane)(PEU) without short chain PEI800. Both PEU-g-PEI800 and PEU, readily self-assembled with plasmid DNA (pCMV-betagal) in a HEPES buffer, were characterized by dynamic light scattering and zeta-potential. The results reveal that PEU-g-PEI800 and PEU were able to self-assemble particles with DNA and yield nano-sized complexes (<200nm) with positive charge at N/P ratios of 20/1 and 120/1, respectively.

Synthesis and characterizations of new lysine-based biodegradable cationic poly(urethane-co-ester) and study on self-assembled nanoparticles with DNA.

To improve the self-assembly efficiency of nanoparticles with DNA, we synthesized lysine-based poly(urethane-co-ester) PMMD (6) and polyester PDMA (8) bearing ester linkages in the backbone and tertiary amines in the side chain. Both poly(urethane-co-ester) PMMD (6) and polyester PDMA (8), readily self-assembled with plasmid DNA (pCMV-beta-gal) in HEPES buffer, were characterized by dynamic light scattering and zeta-potential. The results reveal that PMMD (6) and PDMA (8) were able to self-assemble particles with DNA and yield complexes with positive charges of 80-115 nm and 170-180 nm in size at mass ratios (W/W) of 2/1 and 20/1, respectively.

The synthesis of cationic polyurethanes to study the effect of amines and structures on their DNA transfection potential.

Polyurethanes (PUs) are a class of biodegradable polymers that have been applied as tissue-engineering materials with minimum toxicity. In our study, a new series of cationic PUs containing tertiary amines in the backbone and primary, secondary and tertiary amines in the side chains (PU1, PU2 and PU3, respectively) was synthesized and used as nonviral vectors for gene delivery. In addition, we introduced glycidol into the structure of PU for greater solubility and biocompatibility and grafted various amines in the side chains (PUg1, PUg2, PUg3).

Platelet adsorption and hemolytic properties of liquid crystal/composite polymers.

The aim of this study is to investigate how the presence of liquid crystal, cholesteryl oleyl carbonate, embedded into polymers (PMMA, Eb270, PU) affects the biocompatibility of composite membranes with human blood. The effects of different surface textures of composite membranes on platelet adhesion and platelet activation were evaluated as well. The adhesion and geometric deformation of platelets were demonstrated by SEM.

Effect of molecular weight on the transfection efficiency of novel polyurethane as a biodegradable gene vector.

New polyurethane 2-diethylaminoethylamine-polyurethane (LGEA-PU) containing poly(ethylene glycol) segments and tertiary amines was synthesized. LGEA-PU self-assembled readily with the plasmid DNA (pCMV-betagal) in HEPES buffer and was characterized by dynamic light scattering, zeta potential, atomic force microscopy, and XTT cell viability assays. To examine the effect of molecular weight of LGEA-PU systems on transfection, LGEA-PU systems of four different molecular weights (LGEA-PU99, LGEA-PU59, LGEA-PU24, and LGEA-PU7) were prepared.

Structural characterization and buffering capacity in relation to the transfection efficiency of biodegradable polyurethane.

Inefficient release of polymer/DNA complexes from endocytic vesicles into the cytoplasm and the cytotoxic nature of cationic polymers are two of the primary causes of poor gene delivery. EG-polyurethane [poly(ethylene glycol)-PU, Poly 1], EGDM-polyurethane [poly(ethylene glycol), 2-(dimethylamino)ethylamine-PU, Poly 2], and MDEADM-polyurethane [N-methyldiethanolamine, 2-(dimethylamino)ethylamine-PU, Poly 3] were designed in this study to overcome these obstacles. The structural characteristics of polyurethanes and physicochemical properties of their formed complexes with DNA were determined to correlate their transfection efficiency.

Synthesis of novel biodegradable cationic polymer: N,N-diethylethylenediamine polyurethane as a gene carrier.

A new cationic polymer, N,N-diethylethylenediamine-polyurethane (DEDA-PU), bearing tertiary amines in the backbone and side chains, was synthesized and used as a nonviral vector for gene delivery. The DEDA-PU readily self-assembled with the plasmid DNA (pCMV-betagal) in water and buffer at physiological pH, as determined by agarose gel retardation, dynamic light scattering, zeta potential, atomic force microscopy (AFM), and restriction endonuclease protection assays. The results revealed that DEDA-PU was able to bind with plasmid DNA, yielding positively charged complexes with a size around 100 nm at a DEDA-PU/DNA ratio of 50/1 (w/w).

A thermodynamic study of cationic polymer-plasmid DNA complexes by highly-sensitive differential scanning calorimetry.

The characteristics of polymer-DNA complexes formed by positively-negatively charged interaction have a great influence on their transfection potential. Since the limit changes in thermal transitions which were hardly measured in conventional calorimetry, now in this study they have been successfully carried out by highly-sensitive differential scanning calorimetry for better understanding the pDMAEMA-plasmid DNA complexing process. Thermal behaviors of plasmid DNA, polymer and their formed complexes were recorded to give insights into their conformational changes when temperature was raised.