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Two polyethylene oxide-based delivery systems comprised of reacting PEG polymers were designed for the delivery of DNA expression vectors. The polymers are formulated with the DNA and injected into the muscle, wherein a crosslinked matrix forms in-situ. The matrix resembles a viscous solution (formulation A) or a gel (formulation B). The reacting PEG polymers do not interact with, but entrap the DNA. The formation of the matrix does not affect the supercoiling of the incorporated DNA. The polymers are biocompatible and biodegradable due to the presence of hydrolytically labile bonds in one of the components. Measurement of degradation in vivo suggests that a significant amount of the polymer disappears from the injected muscle by 28 days post injection. Administration to mice of SEAP plasmid DNA formulated with the PEG polymers results in SEAP expression. Expression levels are similar to those of unformulated DNA, but the duration of gene expression is significantly longer in immunocompetent animals receiving the formulated DNA. Significantly lower anti-SEAP IgG titers are elicited by network-formulated DNA relative to unformulated DNA, even though expression levels are comparable. The data suggests that the matrix extends duration of expression by reducing the anti-SEAP immune response so that these delivery systems may be useful for prolonged gene expression following a single intramuscular injection.

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Cholesteric liquid crystalline phases were observed in dimethyl sulfoxide solutions of a new chitosan derivative. This chitosan derivative had a substitution pattern which approximates that of 3,6-0-(butyl carbamate)-N-phthaloyl chitosan (BuCaPhCh). UV-visible and circular dichroic (CD) spectroscopy carried out on BuCaPhCh revealed that the cholesteric pitch is in the visible wavelength (X) region and is left-handed for all investigated polymer weight fraction, x, values (0.50, 0.56, 0.60, and 0.70) and solution temperatures (25-88 °C). The apparent absorption maxima, Xa, due to selective reflection of the cholesteric phases, showed a very strong variation as x was decreased to a value near the isotropic-anisotropic solution liquid crystal transition. The change in pitch as a function of temperature (dP/dT) was negative for all of the polymer weight fractions investigated. It was determined that the pitch-temperature relationship was dissimilar in two different temperature regions: (I) °°>|1 -TJT] > 1.25 and (II) 1.25 > |1 -TJT\ > 0, where Tc is the clearing temperature. Use of the empirical relationship (1/Xa) ~(1 -TJT)' showed that the exponent, v, within the normalized temperature region II, varies considerably (0.05-0.22) as a function of the x value, whereas, in the normalized temperature region I, v is almost independent of the x value. A comparison was carried out of the experimental pitch-temperature-concentration relationships determined herein relative to that expected on the basis of theoretical relationships proposed by Varichon, Ten Bosch, and Sixou (Liq. Cryst. 1991, 9, 701). It was found that there was very good agreement between theory and experiment for pitch-polymer concentration dependence. In contrast, the experimental pitch-temperature dependence showed poor agreement with that expected on the basis of theoretical predictions.

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A method for the direct observation and measurement of micelles has been developed. At higher solution concentrations, multi-angle laser light scattering in batch mode was used, and at lower concentrations, Size Exclusion Chromatography with dual detection (Light Scattering and Refractive Index) was employed. Micelle formation for PEG and a copolymer of PEG with lactate and acrylate groups (8KLX) were observed using this method. The critical concentrations for the micelle formation were determined for the PEG and 8KLX macromolecules. Confirmation of the results was obtained using an independent spectrophotometric method.The phenomena of macromolecular association, complexation and micelle formation occupy a very important place in polymer and biopolymer chemistry. All of these phenomena are strongly dependent upon the concentration of the macromolecules in solution. The size and number of the macromolecular aggregates in solution increase with increasing concentration.Size Exclusion Chromatography (SEC) l\l is one of the most reliable methods for the determination of molecular weight and size of macromolecules in solution. In principle, this method may be used for the corresponding characterization of macromolecular aggregates. However, aggregation normally occurs at concentration levels higher than those used in SEC. Common SEC solute concentrations range from 1% to 5%, and after passing through the chromatographic system, are diluted by a factor of 30-50. As a result, when the solutions reach the detector cell, their concentration is less 0.1%. Frequentiy, such concentration levels are not enough for aggregate formation, and direct determination of molecular weights and sizes of these macromolecular aggregates becomes impossible.The use of SEC with two detectors on line (multi-angle light scattering, LS, and refractive index, RI) affords a new opportunity to observe these aggregates directly in