Water-soluble nanoparticles from random copolymer and oppositely charged surfactant, 3a. Nanoparticles of poly(ethylene glycol)-based cationic random copolymer and fatty acid salts.

In this report, we investigate the nanoparticle formation between random copolymers (RCPs) of methoxy-poly(ethylene glycol) monomethacrylate (MePEGMA) and (3-(methacryloylamino)propyl)trimethylammonium chloride (MAPTAC) and oppositely charged natural surfactants, sodium oleate and sodium laurate, using turbidimetric titration, steady-state fluorescence, dynamic light scattering, and electron microscopy. Though sodium oleate and sodium laurate are sparingly soluble in water, the nanoparticle complexes formed between the RCPs and these surfactants are soluble in the entire range of compositions studied here, including the stoichiometric electronetural complexes. The spherical nature of these nanoparticle complexes is revealed by electron microscopic (EM) analysis. Dynamic light scattering (DLS) showed that the average diameters of the nanoparticles are in the range 50 to 150 nm, which is supported by EM analysis. Pyrene fluorescence experiments suggested that these soluble nanoparticles have hydrophobic cores, which may solubilize hydrophobic drug molecules. The polarity index (I(1)/I(3)) obtained from the pyrene fluorescence spectra and the conductometric measurements showed that the critical concentration of fatty acid salts needed to obtain nanoparticles are in the order of 10(-4) M. Further, the complexation of such poorly water-soluble amphiphilic surfactants with polymers offers a useful method for the immobilization of hydrophobic compounds towards water-soluble drug carrier formulations. The formation of water-soluble nanoparticles by the self-assembly of fatty acid salts upon interacting with oppositely charged poly(ethylene glycol)-based polyions.

Water-soluble complexes from random copolymer and oppositely charged surfactant. 2. Complexes of poly(ethylene glycol)-based cationic random copolymer and bile salts.

The complexes formed between the positively charged random copolymers (RCPs) of methoxy-poly(ethylene glycol) monomethacrylate (MePEGMA) and (3-(methacryloylamino)propyl)trimethylammonium chloride (MAPTAC) with oppositely charged biosurfactants (bile salts) were studied using turbidimetric titration, steady-state fluorescence, dynamic light scattering, and electron microscopy. Studies showed that the complexes of the RCPs of MAPTAC and MePEGMA with less than 68 mol % of PEG content precipitate in water, whereas the complexes of the copolymer with 89 and 94 mol % of PEG content do not precipitate in the entire range of composition of the mixture including stoichiometric compositions when the electroneutral complexes are formed. The complexes with true hydrophobic domains, which are a prerequisite characteristic to serve as a carrier, can be obtained at much lower concentration than the critical micelle concentration of the corresponding surfactant. For a particular surfactant, hydrophobic domains are obtained at lower Z-/+ for the random copolymer with lower PEG content. The hydrodynamic radii of these complexes vary over a range of 20-35 nm. Overall results reveal that these complexes are qualitatively similar to the polyion complex micelles or block ionomer complexes obtained from the block copolymers and oppositely charged surfactants. As the surfactants used in this study are biocompatible, we hope that these soluble particles will be promising vectors in the field of drug delivery.

Complexes of poly(ethylene glycol)-based cationic random copolymer and calf thymus DNA: a complete biophysical characterization.

Complete biophysical characterization of complexes (polyplexes) of cationic polymers and DNA is needed to understand the mechanism underlying nonviral therapeutic gene transfer. In this article, we propose a new series of synthesized random cationic polymers (RCPs) from methoxy poly(ethylene glycol) monomethacrylate (MePEGMA) and (3-(methacryloylamino)propyl)trimethylammonium chloride with different mole ratios (32:68, 11:89, and 6:94) which could be used as a model system to address and answer the basic questions relating to the mechanism of the interaction of calf thymus DNA (CT-DNA) and cationic polymers. The solubility of the complexes of CT-DNA and RCP was followed by turbidity measurements. It has been observed that complexes of RCP with 68 mol % MePEGMA precipitate near the charge neutralization point, whereas complexes of the other two polymers are water-soluble and stable at all compositions. Dnase 1 digestion experiments show that DNA is inaccessible when it forms complexes with RCP. Ethidium bromide exclusion and gel electrophoretic mobility show that both polymers are capable of binding with CT-DNA. Atomic force microscopy images in conjunction with light scattering experiments showed that the complexes are spherical in nature and 75-100 nm in diameter. Circular dichroism spectroscopy studies indicated that the secondary structure of DNA in the complexes is not perturbed due to the presence of poly(ethylene glycol) segments in the polymer. Furthermore, we used a combination of spectroscopic and calorimetric techniques to determine complete thermodynamic profiles accompanying the helix-coil transition of CT-DNA in the complexes. UV and differential scanning calorimetry melting experiments revealed that DNA in the complexes is more stable than in the free state and the extent of stability depends on the polymer composition. Isothermal titration calorimetry experiments showed that the binding of these RCPs to CT-DNA is associated with small exothermic enthalpy changes. A complete thermodynamic profile showed that the RCP/DNA complex formation is entropically favorable. Much broader opportunities to vary the architecture of the polymers studied here make these systems promising in addressing various basic and practical problems in gene delivery systems.

Probing the association behavior of poly(ethylene glycol)-based amphiphilic comb-like polymer in NaCl solution.

The effect of salt on the associative behavior of intramolecular aggregates obtained from poly(ethylene glycol)-based amphiphilic comb-like polymers in aqueous medium at pH 6.2 has been investigated by surface tension, fluorescence probe, dynamic light-scattering, and viscometry techniques. Results reveal that the addition of salt screens the electrostatic repulsion between the charges along the polymer backbone in the aggregates and consequently (1) reduces the surface activity at the air/water interface, (2) leads to the contraction of the polymer backbone, and (3) reduces the hydrodynamic sizes of the aggregates. In contrast, the hydrophobicity of the aggregates remains unperturbed.

Aggregation and Polymerization of PEG-Based Macromonomers with Methacryloyl Group as the Only Hydrophobic Segment.

Aggregation behavior in aqueous solution of a series of poly (ethylene glycol) (PEG)-based macromonomers with methacryloyl group as the only hydrophobic segment has been investigated using surface tension, steady-state and time-resolved fluorescence spectroscopy using pyrene as a probe, and small-angle neutron scattering techniques. The general formula of these macromonomers is CH(2)&dbond;C(CH(3))-CO-O-E(m)-CH(3), where E is the ethylene glycol unit and m=8 (ME(8)), 18 (ME(18)), 49 (ME(49)), and 120 (ME(120)). The results indicate that a macromonomer with 8 ethylene glycol units forms as an aggregate above a certain critical concentration, which can be defined as critical aggregation concentration. The observed high value of I(1)/I(3) in pyrene emission spectra at the interface of these aggregates and the inability to scatter a neutron beam by these aggregates indicate that the hydrophobic cluster formed by this macromonomer is remarkably solvated. ME(18) has a tendency to aggregate but others do not form any hydrophobic cluster. The homopolymerization behaviors of these macromonomers in an aqueous medium at 70 degrees C are consistent with these possibi- lities. Copyright 2001 Academic Press.