Polyoxazoline polymers with methyl (PMOZ), ethyl (PEOZ), and propyl (PPOZ) side chains were prepared by the living cationic polymerization method and purified by ion-exchange chromatography. The following properties of polyoxazoline (POZ) were measured: apparent hydrodynamic radius by aqueous size-exclusion chromatography, relative lipophilicity by reverse-phase chromatography, and viscosity by cone-plate viscometry. The PEOZ polymers of different molecular weights were first functionalized and then conjugated to model biomolecules such as bovine serum albumin, catalase, ribonuclease, uricase, and insulin. The conjugates of catalase, uricase, and ribonuclease were tested for in vitro activity using substrate-specific reaction methods. The conjugates of insulin were tested for glucose lowering activity by injection to naïve Sprague-Dawley rats. The conjugates of BSA were injected into New Zealand white rabbits and serum samples were collected periodically and tested for antibodies to BSA. The safety of POZ was also determined by acute and chronic dosing to rats. The results showed that linear polymers of POZ with molecular weights of 1 to 40 kDa can easily be made with polydispersity values below 1.10. Chromatography results showed that PMOZ and PEOZ have a hydrodynamic volume slightly lower than PEG; PEOZ is more lipophilic than PMOZ and PEG; and PEOZ is significantly less viscous than PEG especially at the higher molecular weights. When PEOZ was attached to the enzymes catalase, ribonuclease, and uricase, the in vitro activity of the resultant bioconjugates depended on the extent of protein modification. POZ conjugates of insulin lowered blood glucose levels for a period of 8 h when compared to 2 h for insulin alone. PEOZ, like PEG, was also able to successfully attenuate the immunogenic properties of BSA. The POZ polymers (10 and 20 kDa) are safe when administered intravenously to rats, and the maximum tolerated dose (MTD) was greater than 2 g/kg. Blood counts, serum chemistry, organ weights, and the histopathology of key organs were normal. These results conclude that POZ has the desired drug delivery properties for a new biopolymer.

New methacrylate monomers containing pendant quaternary ammonium moieties based on 1,4-diazabicyclo-[2.2.2]-octane (DABCO) were synthesized. The DABCO group contains either a butyl or a hexyl pendant group comprising the hydrophobic segment of the monomers and one tether group to the methacrylate moiety. The monomers were homopolymerized in water by using 2,2Ј-azobis(2-methylpropionamide) dihydrochloride (V-50) as an initiator. The monomers and polymers were characterized by elemental analysis, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), FTIR, and 13 C-NMR. The antimicrobial activities of the corresponding small molecules (bis-quaternary ammonium monocarboxylates) and polymers were investigated against Staphylococcus aureus and Escherichia coli. Although the small molecules did not show any antimicrobial activity, the polymers were moderately effective against both Gram-positive and Gramnegative bacteria. The minimum inhibitory concentration (MIC) values of the polymers with butyl and hexyl hydrocarbon chains against S. aureus and E. coli were found to be 250 and 62.5 g/mL, respectively. The minimum bactericidal concentration (MBC) value for the polymer with the butyl group was higher than 1 mg/mL, whereas the MBC value for the polymer with hexyl group was found to be 62.5 g/mL. Thus, an increase of the alkyl chain length from 4 to 6 significantly increased the antimicrobial activity of the polymer.

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New water-soluble methacrylate polymers with pendant quaternary ammonium (QA) groups were synthesized and used as antibacterial materials. The polymers with pendant QA groups were obtained by the reaction of the alkyl halide groups of a previously synthesized functional methacrylate homopolymer with various tertiary alkyl amines containing 12-, 14-, or 16-carbon alkyl chains. The structures of the functional polymer and the polymers with QA groups were confirmed with Fourier transform infrared and 1 H and 13 C NMR. The degree of conversion of alkyl halides to QA sites in each polymer was determined by 1 H NMR to be over 90% in all cases. The number-average molecular weight and polydispersity of the functional polymer were determined by size exclusion chromatography to be 32,500 g/mol and 2.25, respectively. All polymers were thermally stable up to 180 8C according to thermogravimetric analysis. The antibacterial activities of the polymers with pendant QA groups against Staphylococcus aureus and Escherichia coli were determined with broth-dilution and spread-plate methods. All the polymers showed excellent antibacterial activities in the range of 32-256 lg/mL. The antibacterial activity against S. aureus increased with an increase in the alkyl chain length for the ammonium groups, whereas the antibacterial activity against E. coli decreased with increasing alkyl chain length.

A novel methacrylate monomer containing a quinolone moiety was synthesized and homopolymerized in N,N-dimethylformamide (DMF) by using azobisisobutyronitrile (AIBN) as an initiator. The new monomer was copolymerized with poly(ethylene glycol) methyl ether methacrylate (MPEGMA) in DMF using the same initiator. The monomer, homopolymer, and copolymer were characterized by elemental analysis, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), size exclusion chromatography (SEC), FTIR, (13)C NMR, and (1)H NMR. The antibacterial activities of the monomer as well as polymers were investigated against Staphylococcus aureus and Escherichia coli, which are representative of Gram-positive and Gram-negative bacteria, respectively. All compounds showed excellent antibacterial activities against these two types of bacteria. The antibacterial activities were determined using the shaking flask method, where 25 mg/mL concentrations of each compound were tested against 10(5) CFU/mL bacteria solutions. The number of viable bacteria was calculated by using the spread plate method, where 100 microL of the incubated antibacterial agent in bacteria solutions were spread on agar plates and the number of viable bacteria was counted after 24 h of incubation period at 37 degrees C.