Hydrophobic Monomer Units Research Articles

Effects of inner polarity and viscosity of amphiphilic phospholipid polymer aggregates on the solubility enhancement of poorly water-soluble drugs

We quantitatively evaluated the properties of aggregates of amphiphilic polymers formed in an aqueous medium and clarified the effect of the inside polarity and viscosity of the polymer aggregate on the solubilization of poorly water-soluble drugs. Three water-soluble amphiphilic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers with various hydrophobic monomer units, namely, n-butyl methacrylate (BMA), 2-methacryloyloxyethyl butylurethane (MEBU), and 2-methacryloyloxyethyl benzylurethane (MEBZU), were synthesized. The different molecular interactions between the hydrophobic monomer units, such as hydrophobic interactions, hydrogen bonding, and dispersion force between the aromatic rings, were considered. Fluorescence spectroscopic measurements revealed that every polymer aggregate had almost the same polarity as that of ethanol. Also, the polymers with urethane bonds, poly(MPC-co-MEBU) and poly(MPC-co-MEBZU) had slightly higher polarity and viscosity inside the polymer aggregate than that of poly(MPC-co-BMA). The water solubility of nifedipine and indomethacin was clearly enhanced in the MPC polymer aqueous solution depending on the polymer structure. As indomethacin is less soluble in polar solvents than is nifedipine, it needed to be transferred deeper into the polymer aggregates for stable solubilization. It is plausible that the high viscosity inside the polymer aggregate prevented the diffusion of drug molecules. We concluded that not only the polarity inside the polymer aggregates and the strength of the interaction force between the polymer and drug, but also the viscosity inside the polymer aggregates were responsible for enhancing the solubilization of poorly water-soluble drugs.

Thermosensitive self-assembled behavior of poly (acrylamide-co-acrylonitrile)/polystyrene triblock copolymer and application in drug loading

Type poly(acrylamide-co-acrylonitrile) (P(AAm/AN)) is a typical thermosensitive polymer. It has a low solubility for some containing phenyl medicines. Introduction of segments with high affinity to medicines containing phenyl is helpful to improve the solubility for drugs. With the introduction of hydrophobic monomer units styrene, ABA type triblock polymer P(AAm/AN)-b-PS-b-P(AAm/AN) showed thermosensitive self-assembly behavior in aqueous solution. With the increasing of temperature, the triblock polymer experiences a process from to insoluble to from self-assembled structure and finally soluble. Accordingly, drug can be encapsulated, partly released, and completely released. This triblock polymer has the potential application in load drug release.

Facile synthesis of cauliflower-like hydrophobically modified polyacrylamide nanospheres by aerosol-photopolymerization

Amphiphilic copolymers consist of hydrophilic and hydrophobic monomer units have attracted great technological attention recently, owing to their unique properties and their ability to stabilize various interfaces in aqueous systems. This paper presents a novel and facile approach to produce spherical polyacrylamide, polystyrene and hydrophobically modified polyacrylamide (HM-PAM), as one of the most important type of amphiphilic copolymers, using a continuous aerosol-photopolymerization for the first time. To this end, the monomer droplets were generated by an atomizer, then photopolymerization was initiated ‘‘in flight’’ by ultraviolet (UV) irradiation of the aerosol monomer droplets containing photoinitiator within the average aerosol residence time of 30s in the photoreactor. To control the aqueous solubility, size and morphology of the resulting HM-PAM copolymers, different styrene/acrylamide monomer concentrations were introduced to the system. The textural properties of the obtained materials were characterized by TEM, SEM and N2 adsorption-desorption isotherms. The results revealed that the copolymers and polyacrylamide have cauliflower-like morphologies, while polystyrene has a nearly smooth morphology. Moreover, chemical compositions of the obtained materials were investigated by several characterization techniques such as 1H NMR, FT-IR, TGA and elemental analysis. 1H NMR and elemental analysis of resulting copolymers microstructures displayed successful incorporation of styrene in copolymer with a good agreement compared to initial ratios. The production of amphiphilic copolymer of acrylamide and styrene using the facile aerosol-photopolymerization method might open new avenues to produce various amphiphilic copolymers with a variety of hydrophobic and hydrophilic monomers with desirable properties.

Intracellular trafficking pathways for nuclear delivery of plasmid DNA complexed with highly efficient endosome escape polymers.

Understanding the pathways for nuclear entry could see vast improvements in polymer design for the delivery of genetic materials to cells. Here, we use a novel diblock copolymer complexed with plasmid DNA (pDNA) to determine both its cellular entry and nuclear pathways. The diblock copolymer (A-C3) is specifically designed to bind and protect pDNA, release it at a specific time, but more importantly, rapidly escape the endosome. The copolymer was taken up by HEK293 cells preferentially via the clathrin-mediated endocytosis (CME) pathway, and the pDNA entered the nucleus to produce high gene expression levels in all cells after 48 h, a similar observation to the commercially available polymer transfection agent, PEI Max. This demonstrates that the polymers must first escape the endosome and then mediate transport of pDNA to the nucleus for occurrence of gene expression. The amount of pDNA within the nucleus was found to be higher for our A-C3 polymer than PEI Max, with our polymer delivering 7 times more pDNA than PEI Max after 24 h. We further found that entry into the nucleus was primarily through the small nuclear pores and did not occur during mitosis when the nuclear envelope becomes compromised. The observation that the polymers are also found in the nucleus supports the hypothesis that the large pDNA/polymer complex (size ~200 nm) must dissociate prior to nucleus entry and that cationic and hydrophobic monomer units on the polymer may facilitate active transport of the pDNA through the nuclear pore.

Blood cell separation using crosslinkable copolymers containing N,N‐dimethylacrylamide

AbstractAmphiphilic copolymers using hydrophilic N,N‐dimethylacrylamide (DMA), hydrophobic methyl methacrylate (MMA) and a crosslinkable monomer, 3‐methacryloyloxypropyl trimethoxysilane (MTSi), were synthesized and evaluated as coating materials for leukocyte removal filters for whole blood. When filters composed of non‐woven fabrics were coated with crosslinked synthesized copolymers, the elution ratios of the copolymers to water were adequately low because of the crosslinking with trimethoxysilane groups of MTSi units in the copolymers. Filters coated with crosslinked poly(DMA‐co‐MTSi) having a 0.96 mole fraction of DMA units showed a 0.35 ± 0.44% platelet permeation ratio and a logarithmic reduction of 4.0 ± 0.68 for leukocytes. On the other hand, an increase in the content of MMA units in the DMA‐containing copolymers improved the permeation ratio of the platelets dramatically. Filters coated with crosslinked poly(DMA‐co‐MMA‐co‐MTSi) containing a 0.39 mole fraction of MMA units and a 0.58 mole fraction of DMA units showed an 86 ± 3.0% platelet permeation ratio and a logarithmic reduction of 2.1 ± 1.2 for leukocytes. This indicates that an adequate content of hydrophobic monomer units, such as MMA units, is necessary for effective platelet permeation. Copyright © 2007 John Wiley & Sons, Ltd.

Dynamic motion of phosphorylcholine groups at the surface of poly(2-methacryloyloxyethyl phosphorylcholine– random–2,2,2-trifluoroethyl methacrylate)

A series of novel random copolymers composed of hydrophilic and hydrophobic monomer units have been synthesized by a conventional radical polymerization method. As the hydrophilic monomer unit, 2-methacryloyloxyethyl phosphorylcholine (MPC) was selected because the MPC polymers are well known for their excellent bio- and blood compatibilities. The semifluorinated monomer, 2,2,2-trifluoroethyl methacrylate (TFEMA), was used as the hydrophobic monomer. The surface analysis of the copolymer by X-ray photoelectron spectroscopy, dynamic contact angle measurement, and ζ-potential measurement showed that the TFEMA unit was concentrated at the outermost surface in the dry state. The dynamic reorientation of the MPC unit occurred in the wet state because the MPC unit had a strong hydrophilic character. As a result, the monomer unit composition on the surface became almost the same as that in the bulk. Nevertheless, the properties of the surface were hydrophilic in spite of the MPC unit composition of the bulk. In particular, the amount of protein adsorbed on the surface was dramatically reduced when the MPC unit mole fraction was 0.2.

Surface characteristics of block-type copolymer composed of semi-fluorinated and phospholipid segments synthesized by living radical polymerization

A series of random and block copolymers composed of hydrophilic and hydrophobic monomer units have been synthesized by the free and living radical polymerization methods, respectively. The hydrophilic monomer unit, 2-methacryloyloxyethyl phosphorylcholine (MPC), was selected because the MPC polymers are well-known for their excellent bio- and blood compatibilities. The semi-fluorinated monomer, 2,2,2-trifluoroethyl methacrylate (TFEMA), was used as the hydrophobic monomer unit. Several analyses of the copolymer surface showed that the TFEMA unit was concentrated at the outermost surface on the random copolymer surface and characteristics of MPC unit was dominant on the block copolymer with a low-MPC-unit composition in the dry state. A reorientation of the MPC unit occurred dynamically in the wet state because of the strong hydrophilicity of the MPC units. In the case of the block copolymer with a low-MPC-unit composition, the surface was covered with the MPC units in the wet state. As a result, the amount of the adsorbed bovine plasma fibrinogen and bovine serum γ-globulin on the block copolymer surface was reduced dramatically.

Micelle formation in a dilute solution of block copolymers with a polyelectrolyte block complexed with oppositely charged linear chains

The theory of micelle formation in a dilute solution mixture of polyelectrolyte/neutral diblock copolymers and oppositely charged linear chains has been developed. The core of the micelles is formed by the hydrophobic monomer units of polyelectrolyte complexes between the oppositely charged polyions while the hydrophilic uncharged blocks of the block copolymers comprise the micellar corona. The process of the formation of polyelectrolyte complexes and micelles in the solution has been described as sets of association–dissociation reactions with certain chemical constants and the concentration distribution of micellar aggregates of a given composition has been calculated for various concentrations of linear chains and block copolymer macromolecules in the solution. It was shown that the micelles are formed by nearly fully neutralized block copolymers, so that the micellar charge is close to zero. The aggregation number of the micelles and their charge slightly depend on the concentration of the block copolymers as well as the linear chains in the solution. Micelles in the solution coexist with single block copolymer chain/linear polymer complexes of different composition.

Transfection efficiency increases by incorporating hydrophobic monomer units into polymeric gene carriers

The water soluble terpolymer, poly( N-isopropylacrylamide (IPAAm)- co-2-(dimethylamino)ethyl methacrylate (DMAEMA)- co-butylmethacrylate (BMA)) was synthesized, and its efficiency in in vitro gene transfection was evaluated. Copolymers with different compositions were synthesized by radical polymerization. For a series of copolymers containing 60 mol% of DMAEMA, the plasmid bands were retained within the gel loading slot, independent of polymer/plasmid weight ratios or BMA monomer content. In contrast, for a series of copolymers containing 20 mol% DMAEMA, plasmid bands of complexes were retarded with increasing weight ratios. For the copolymer with 10 mol% BMA content, the plasmid was completely retained within the gel loading slot. The transfection efficiency of polymer/plasmid complexes was evaluated in COS-1 cells using a pCMV-lacZ plasmid, encoding for β-galactosidase as a reporter gene. Transfection efficiency of a series of copolymers containing 20 mol% of DMAEMA varied with BMA content. The transfection efficiency of the copolymers with 0, 2, and 5 mol% of BMA was low. The transfection efficiency of the copolymers with 10 mol% of BMA was about 2-fold higher than that of the PDMAEMA control homopolymer. The transfected cells were observed at a very wide range of polymer/plasmid weight ratios. The transfection efficiency of all copolymers containing 60 mol% of DMAEMA was lower than that of the PDMAEMA homopolymer.

Synthesis and characterization of amphiphilic diblock copolymers of methyl tri(ethylene glycol) vinyl ether and isobutyl vinyl ether

Water-soluble diblock copolymers of methyl tri(ethylene glycol) vinyl ether (hydrophilic block) and isobutyl vinyl ether (hydrophobic block) of different molecular weights and composition were synthesized by living cationic polymerization. The molecular weight and comonomer composition of these copolymers were determined by GPC and 1H NMR spectroscopy, respectively. Aqueous solutions of the copolymers were characterized in terms of their micellar behavior using dynamic light scattering, aqueous GPC, and dye solubilization. All the copolymers formed aggregates with the exception of a diblock copolymer with only two hydrophobic monomer units. The micellar hydrodynamic size scaled with the 0.61 power of the number of hydrophobic units, in good agreement with a theoretical exponent of 0.73. An increase in the length of the hydrophobic block at constant hydrophilic block length or an increase in the overall polymer size at constant block length ratio both resulted in lower critical micelle concentrations (cmcs). The cloud points of 1% w/w aqueous solutions of the polymers were determined by turbidimetry. An increase in the length of the hydrophobic block at constant hydrophilic block length caused a decrease in the cloud points of the copolymers. However, an increase in the overall polymer size at constant block length ratio led to an increase in the cloud point. © 1996 John Wiley & Sons, Inc.

Studies of the antenna effect in polymer molecules. XVII. Synthesis and photocatalytic activity of poly(sodium styrenesulfonate‐co‐N‐vinylcarbazole) and poly[sodium styrenesulfonate‐co‐N‐(acryloyloxyhexyl)carbazole

AbstractTwo new antenna polyelectrolytes, poly(sodium styrenesulfonate‐co‐N‐vinylcarbazole) (PSSS–VCz) and poly[sodium styrenesulfonate‐co‐N‐(acryloyloxyhexyl)carbazole](PSSS–AHCz) have been synthesized. Both polymers were found to solubilize large hydrophobic compounds such as perylene in aqueous solution, but PSSS–AHCz was much more efficient than PSSS–VCz. The distribution coefficients of perylene between the polymer pseudophase and water was determined to be (2.9 ± 0.1) × 106 and (4.0 ± 0.2) × 104 in PSSS–AHCz and PSSS–VCz, respectively. The greater solubilizing ability of PSSS–AHCz is attributed to the higher content of hydrophobic monomer units in the polymer. Both copolymers displayed photocatalytic activity, absorbing light in the UV‐visible spectral region. Energy can then be transferred to a solubilized molecule or dissolved oxygen and induce photochemical reactions. The model reaction used in this study was the photosensitized oxidation of perylene solubilized in aqueous polymer solutions. PSSS–AHCz was found to be a much more efficient photocatalyst than PSSS–VCz. The enhanced photocatalytic activity of PSSS–AHCz is attributed to the greater concentration of carbazole chromophores, the higher local concentration of probe in the polymeric pseudophase and possibly to the elimination of the low‐energy excimer.