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 hyperbranched poly(carbosilarylenes) are described that exhibit low glass transition
temperatures and high thermal stabilities. The incorporation of Si−O−Si linkages into the branches
leads to a polymer of increased flexibility but considerably lower thermal stability. The hyperbranched
polymers are prepared via a one-pot hydrosilylation polymerization of aromatic AB3 monomers. The
monomers are prepared from commercially available reagents using lithium−halogen exchange reactions
followed by treatment with chlorosilanes. The glass transition temperatures of the hyperbranched polymers
range from −45 °C for the siloxane-containing polymer to 12 °C for the 1,4-substituted polymer. Number-average molecular weights (GPC) range from 2560 to 5600. The degree of branching in these polymers
was determined by quantitative 29Si NMR spectroscopy and found to be very close to the theoretical
value of 0.44 for AB3 systems.
A straightforward methodology for the synthesis of multifunctionalized dendrimers that is based on an orthogonal functionalization strategy has been developed. Polyamide-based dendrimers that possess both a single aldehyde and a single azide moiety on their periphery have been synthesized by using a convergent synthetic strategy. These dendrimers can be functionalized quantitatively with small organic and biological molecules that contain hydrazide and/or alkyne groups in which each functional moiety is completely specific for its complementary motif. This orthogonal functionalization strategy has the potential to be used to synthesize multifunctional dendrimers for a variety of applications, which range from targeted biological delivery vehicles to optical materials.
Monofunctionalized polyamide-based dendrimers containing either a terminal azide or alkyne moiety have been designed and synthesized via a convergent synthetic approach. The monofunctionalization allows for the single attachment of a functional moiety in quantitative yields by using 1,3-dipolar cycloadditions, thereby opening the possibility for targeted dendrimer functionalization.
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