Costas S. Patrickios

Covalent amphiphilic polymer networks

The recent literature on chemically cross-linked amphiphilic polymer networks is reviewed. The main subjects covered are network synthesis, characterization, modeling and applications. Special mention is made to more modern methods for amphiphilic network synthesis and in particular to those involving controlled polymerization techniques. A key question regarding synthesis is which method gives the most perfect networks. On the characterization side is the issue of microphase separation of amphiphilic networks in water and the morphologies obtained in these systems, in comparison with the morphologies of amphiphilic linear block copolymers in water. Major recent advances: The most important developments of the past year in the field of amphiphilic polymer networks involved mainly new syntheses: cross-linked stars of various star architectures, cross-linked linear chains of various architectures and compositions, poly(tetrahydrofuran)- and poly(propylene fumarate)-based networks, tricomponent networks containing silicon, and cross-linked poly(acrylic acid)-grafted Pluronics. A first crude model was also developed which shows that amphiphilic networks prefer to be mostly in the microphase separated state. Extensive and systematic experimental studies on network microphase separation are yet to be performed.

ABC triblock polymethacrylates: Group transfer polymerization synthesis of the ABC, ACB, and BAC topological isomers and solution characterization

ABC triblock copolymers of methyl methacrylate (MMA), (dimethylamino)-ethyl methacrylate (DMAEMA), and tetrahydropyranyl methacrylate (THPMA) consisting of 12 units of each type of monomer were synthesized by group transfer polymerization (GTP). These were the three topological isomers with differentblock sequences: DMAEMA12-THPMA12-MMA12, DMAEMA12-MMA12-THPMA12, and THPMA12-DMAEMA12-MMA12. The molecular weights and molecular weight distributions of the copolymers were determined by gel permeation chromatography (GPC) in tetrahydrofuran, and their number-average degrees of polymerization and copolymer compositions were calculated by proton nuclear magnetic resonance spectroscopy (1H-NMR). These molecular weights and degrees of polymerization corresponded closely to the values expected from the monomer/initiator ratios. The polydispersities were low as expected for GTP, and ranged from 1.09 to 1.25. The three triblocks were chemically modified by converting the THPMA units to methacrylic acid (MAA) units either by thermolysis or acid hydrolysis. The resulting ABC triblock poly-ampholytes were characterized by 1H-NMR spectroscopy and hydrogen ion titration. Aqueous GPC studies in 1.0M NaCl at pH 8.5 showed that the triblock copolymers form micelles whose size depends on their block sequence.

Synthesis, Characterization, and DNA Adsorption Studies of Ampholytic Model Conetworks Based on Cross-Linked Star Copolymers

Five model conetworks based on cross-linked star ampholytic copolymers were synthesized by group transfer polymerization. The ampholytic copolymers were based on two hydrophilic monomers: the positively ionizable 2-(dimethylamino)ethyl methacrylate (DMAEMA) and the negatively ionizable methacrylic acid (MAA). Ethylene glycol dimethacrylate was used as the cross-linker. These five ampholytic model conetworks were isomers based on equimolar DMAEMA-MAA copolymer stars of different architectures: heteroarm (two), star block (two), and statistical. The two networks based on the homopolymer stars were also synthesized. The MAA units were introduced via the polymerization of tetrahydropyranyl methacrylate and the acid hydrolysis of the latter after network formation. All the precursors to the (co)networks were characterized in terms of their molecular weights using gel permeation chromatography (GPC). The mass of the extractables from the (co)networks was measured and characterized in terms of molecular weight and composition using GPC and proton nuclear magnetic resonance (1H NMR) spectroscopy, respectively. The degrees of swelling (DS) of all the ampholytic conetworks were measured as a function of pH and were found to present a minimum at a pH value which was taken as the isoelectric point, pI. The DS and the pI values did not present a dependence on conetwork architecture. Finally, DNA adsorption studies onto the ampholyte conetworks indicated that DNA binding was governed by electrostatics.

Hydrophilic Cationic Star Homopolymers Based on a Novel Diethanol-N-Methylamine Dimethacrylate Cross-Linker for siRNA Transfection: Synthesis, Characterization, and Evaluation

Four cationic hydrophilic star homopolymers based on the novel hydrophilic, positively ionizable cross-linker bis(methacryloyloxyethyl)methylamine (BMEMA) were synthesized using sequential group transfer polymerization (GTP) and were, subsequently, evaluated for their ability to deliver siRNA to mouse myoblast cells. The nominal degrees of polymerization (DP) of the arms were varied from 10 to 50. For the polymerizations, 2-(dimethylamino)ethyl methacrylate (DMAEMA) was employed as the hydrophilic, positively ionizable monomer. For comparison, four linear DMAEMA homopolymers were also synthesized, whose nominal DPs were the same as those of the arms of the stars. The numbers of arms of the star homopolymers were determined using gel permeation chromatography with static light scattering detection, and found to range from 7 to 19, whereas the hydrodynamic diameters of the star homopolymers in aqueous solution were measured using dynamic light scattering and found to increase with the arm DP from 13 to 26 nm. The presence of the hydrophilic BMEMA cross-linker enabled the solubility of all star homopolymers in pure water. The cloud points of the star homopolymers in aqueous solution increased with the arm DP from 23 to 29 °C, while the cloud points of the linear homopolymers were found to decrease with their DP, from 42 to 32 °C. The effective pK values of the DMAEMA units were in the range of 6.9 to 7.3 for the star homopolymers, whereas they ranged between 7.3 and 7.4 for the linear homopolymers. Subsequently, all star and linear homopolymers were evaluated for their ability to deliver siRNA to the C2C12 mouse myoblast cell line, expressing the reporter enhanced green fluorescent protein (EGFP). All star homopolymers and the largest linear homopolymer presented significant EGFP suppression, whereas the smaller linear homopolymers were much less efficient. For all star homopolymers and the largest linear homopolymer both the EGFP suppression and the cell toxicity increased with polymer loading. The siRNA-specific EGFP suppression, calculated by subtracting the effect of cell toxicity on EGFP suppression, slightly increased with star polymer loading for the two smaller stars, whereas it presented a shallow maximum and a decrease for the other two stars. Moreover, the siRNA-specific EGFP suppression also increased slightly with the DP of the arms of the DMAEMA star homopolymers. Overall, the EGFP suppression efficiencies with the present star homopolymers were at levels comparable to that of the commercially available transfection reagent Lipofectamine.

Synthesis and aqueous solution characterization of novel diblock polyampholytes containing imidazole

Abstract A series of diblock copolymers of 2-(1-imidazolyl)ethyl methacrylate and tetrahydropyranyl methacrylate (THPMA) were synthesized by group transfer polymerization using propylene carbonate rather than tetrahydrofuran as the solvent to ensure homogeneous polymerizations. The resulting copolymers were characterized by gel permeation chromatography and proton nuclear magnetic resonance spectroscopy (1H NMR) to determine their molecular weights and compositions, respectively. The THPMA units of the copolymers were subsequently converted to methacrylic acid units by acid hydrolysis. The resulting polyampholytes were characterized in terms of their composition and solubility characteristics using 1H NMR and hydrogen ion titration. Moreover, dynamic light scattering in alkaline water (pH 9.3) indicated the presence of large non-micellar aggregates of the block polyampholytes.

Amphiphilic diblock and ABC triblock methacrylate copolymers: synthesis and aqueous solution characterization

Abstract Three isomeric, linear, equimolar, amphiphilic ABC triblock copolymers comprising methyl methacrylate (MMA, nonionic hydrophobic), 2-(dimethylamino)ethyl methacrylate, (DMAEMA, ionizable hydrophilic) and hexa(ethylene glycol) methacrylate (HEGMA, nonionic hydrophilic) units (10 units in each block) were synthesized by group transfer polymerization (GTP). These were the three block sequence isomers, ABC, ACB and BAC. The corresponding random terpolymer was also prepared. The molecular weights and compositions of all the polymers were characterized by GPC and 1H NMR. Measurements of the hydrodynamic diameters and cloud points of the copolymers in aqueous solution suggest that the various distributions of monomer units in the four terpolymers (the three triblocks and the random) result in different supramolecular structures with different colloidal stabilities.

End-linked, amphiphilic, degradable polymer conetworks: synthesis by sequential atom transfer radical polymerization using a bifunctional, cleavable initiator

End-linked, degradable, amphiphilic polymer conetworks (APCNs) of various compositions and architectures were synthesized by sequential atom transfer radical terpolymerization of monomers and cross-linker using a cleavable, bifunctional initiator, bearing two acid-labile hemiacetal ester groups. The incorporation of the initiator residue into the conetworks rendered them cleavable in the middle of their elastic polymer chains. The temporal evolution of the swollen mass of the conetworks in acidified THF–water mixtures was studied and it was determined that the APCN hydrolysis rates were dependent on both conetwork composition and architecture. Regarding the former, hydrophobic APCNs degraded slowly or they even did not dissolve at all. Regarding the latter, conetworks with hydrophobic monomer and hydrophobic cross-linker units distributed around the initiator fragment also dissolved more slowly or they did not degrade at all. Finally, characterization of the star copolymers, produced from conetwork hydrolysis, allowed the determination of the APCN core functionality to be around 30.

Synthesis and characterization of the swelling and mechanical properties of amphiphilic ionizable model co-networks containing n-butyl methacrylate hydrophobic blocks

Amphiphilic ionizable model co-networks based on near-monodisperse, linear ABA and BAB triblock and statistical copolymers of 2-(dimethylamino)ethyl methacrylate (DMAEMA, hydrophilic ionizable) and n-butyl methacrylate (BuMA, hydrophobic non-ionic) were synthesized using group-transfer polymerization in tetrahydrofuran (THF) with the use of the hydrophobic ethylene glycol dimethacrylate (EGDMA) as cross-linker. Seven model co-networks were prepared in which the architecture and copolymer composition were varied systematically. One randomly cross-linked copolymer co-network was also prepared. The co-networks were characterized in terms of their degree of swelling in water as a function of pH and in THF. An increase in the aqueous degree of swelling was observed below pH 6 because of the ionization of the DMAEMA residues. The aqueous degrees of swelling at low pH decreased with the co-network composition in hydrophobic BuMA units. The maximum aqueous degrees of swelling of the copolymer co-networks were architecture-dependent, with the co-networks comprising the statistical copolymer chains swelling about 4 times more than their triblock copolymer counterparts. This was attributed to microphase separation in the triblock copolymer co-networks, which reduced the effective chain length between cross-links due to the collapse of the hydrophobic blocks. The mechanical properties of the water-swollen co-networks at pH 3 and 9 were investigated by determining the co-network uniaxial compression modulus. This modulus was higher at pH 9 than 3, and increased linearly with the BuMA content.

Synthesis and aqueous solution characterization of catalytically active homopolymers, block copolymers and networks containing imidazole

Abstract Imidazole-containing polymers were prepared and characterized in terms of their hydrolytic activity. Unlike similar materials synthesized in the 1960s, the polymers are of precise molecular weight and controlled structure (random or block) afforded by the group transfer polymerization (GTP) chemistry used in the synthetic procedure. The size and composition of the copolymers were determined by gel permeation chromatography (GPC) and proton nuclear magnetic resonance spectroscopy, respectively. Aqueous solutions of the polymers were evaluated in terms of their ability to hydrolyze 4-nitrophenyl acetate. The effects of pH, polymer concentration, substrate concentration, polymer size, and structure were investigated and discussed with reference to the nucleophilicity of imidazole and the self-assembly of the block copolymers into micelles. A series of model networks based on imidazole homopolymers were also prepared and characterized in terms of their aqueous degree of swelling.

Water-soluble ABC triblock copolymers based on vinyl ethers: Synthesis by living cationic polymerization and solution characterization

Water-soluble ABC triblock copolymers of methyl vinyl ether (MVE), ethyl vinyl ether (EVE), and methyl tri(ethylene glycol) vinyl ether (MTEGVE) of various block sequences and carrying 20 monomer units in each block were synthesized by living cationic polymerization. In addition to the triblocks, one AB diblock, one BA diblock, and one statistical copolymer of MVE and MTEGVE carrying 20 units of each type of monomer were synthesized as controls. Moreover, three homopolymers each carrying 20 units of MVE and end groups of varying hydrophobicity were synthesized using three different initiators. The molecular weights and molecular weight distributions of all the polymers were determined by gel permeation chromatography (GPC) in tetrahydrofuran (THF). The number average degrees of polymerization (DP n s) and composition of all the polymers were calculated by proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy. The molecular weights and degrees of polymerization corresponded to the values expected from the monomer/initiator ratios. The calculated polydispersities were reasonably narrow at 1.3. Aqueous GPC studies at room temperature on the triblock copolymers showed that the polymers exist as isolated chains (unimers) in solution but they tend to assemble and form micelles in the presence of a sufficiently high salt concentration apparently due to the insolubility of the EVE units under the latter conditions. Triblocks with a different block sequence exhibited a different susceptibility to salt-induced micellization, as indicated by the retention volume of the micelles and the relative micelle/unimer peak areas. Similarly, the cloud points of the triblock copolymers covered a relatively wide temperature range from 56 to 72°C. These differences in micellization and cloud points suggest a profound effect of the location of the hydrophilic MTEGVE block on copolymer association.