Ethyl Phosphorylcholine Research Articles

Hydrophobic Nature of Methacrylate-POSS in Combination with 2-(Methacryloyloxy)ethyl Phosphorylcholine for Enhanced Solubility and Controlled Release of Paclitaxel.

Amphiphilic copolymers consisting of 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) and hydrophobic monomers are known as biomaterials for the administration of poorly water-soluble drugs such as paclitaxel (PTX). However, the hydrophobic monomers to be copolymerized with MPC have not been optimized for PTX solubilization and its dosage forms. Here, we show the enhanced PTX solubility by only an MPC-based amphiphilic copolymer using a polyhedral oligomeric silsesquioxane (POSS) methacrylate (MA) bearing an ethyl (C2H5) group as a vertex group. MPC was copolymerized with POSS methacrylates bearing different vertex groups of ethyl (C2H5), hexyl (C6H13), and octyl (C8H17) via radical polymerization. We found that the strong interaction between C2H5-POSS and PTX contributed to the slow release of PTX without any burst release. The C2H5-POSS-MA MPC copolymer was internalized into the cultured HeLa cells, which was confirmed by using a fluorescein-4-isothiocyanate (FITC)-labeled PTX, and the PTX-dissolved copolymer induced cell death. We anticipate that the C2H5-POSS-MA MPC copolymer is a good solubilizer bearing a controlled release function for PTX.

Biomimetic Polymer-Based Method for Selective Capture of C-Reactive Protein in Biological Fluids.

Selective capturing and purification of C-reactive protein (CRP) from complex biological fluids plays a pivotal role in studying biological activities of CRP in various diseases. However, obvious nonspecific adsorption of proteins was observed on current affinity sorbents, and thus additional purification steps are often required, which could compromise the recovery of the target protein and/or introduce new impurities. In this study, inspired by the highly specific interaction between CRP and the cell membrane, an excellent anti-biofouling compound 2-(methacryloyloxy)ethyl phosphorylcholine and a highly hydrophilic crosslinker N, N'-methylenebisacrylamide were employed to fabricate a novel cell membrane biomimetic polymer for selective capture of CRP in the presence of calcium ions. Based on the polymer described above, a facile enrichment approach was established after systematic optimization of the washing and elution conditions. With its favorable properties, such as good porosity, weak electrostatic interaction, high hydrophilicity, and biocompatibility, the novel biomimetic polymer exhibits good specificity, selectivity, recovery (near 100%), purity (95%), and a lower nonspecific protein adsorption for CRP in comparison with commercial immobilized p-aminophenyl phosphoryl choline gel and other purification materials. Furthermore, the structural integrity and functionality of CRP in the elution fraction were well preserved and confirmed by circular dichroism spectroscopy, fluorescence spectroscopy, and immunoturbidimetric assay. Finally, the biomimetic polymer was successfully applied to the selective enrichment of CRP from sera of patients with inflammation and rats. The proposed novel enrichment approach based on the versatile biomimetic polymer can be used for effective CRP purification, which will benefit the in-depth study of its biological roles.

Zwitterionic Reduction-Activated Supramolecular Prodrug Nanocarriers for Photodynamic Ablation of Cancer Cells.

An adamantane-containing zwitterionic copolymer poly(2-(methacryloyloxy)ethyl phosphorylcholine)- co-poly(2-(methacryloyloxy)ethyl adamantane-1-carboxylate) (poly(MPC- co-MAda)) was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The hydrophobic photosensitizer chlorin e6 (Ce6) was conjugated to β-cyclodextrin (β-CD) by glutathione (GSH)-sensitive disulfide bonds. The Ce6 conjugated supramolecular prodrug nanocarriers were fabricated due to the host-guest interaction between adamantane and β-CD, which was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The Ce6 conjugated prodrug nanocarriers showed reduction-responsive release of Ce6, which could result in the activation of Ce6. The generation of cytotoxic reactive oxygen species (ROS) was significantly enhanced due to the activation of Ce6. In additiona, the Ce6 conjugated prodrug nanocarriers could effectively inhibit the proliferation of cancer cells upon light irradiation.

Bottom-Up Evolution of Vesicles from Disks to High-Genus Polymersomes

SummaryPolymersomes are vesicles formed by the self-assembly of amphiphilic copolymers in water. They represent one of the most promising alternatives of natural vesicles as they add new possibilities in the amphiphiles' molecular engineering of aqueous compartments. Here we report the design of polymersomes using a bottom-up approach wherein self-assembly of amphiphilic copolymers poly(2-(methacryloyloxy) ethyl phosphorylcholine)-poly(2-(diisopropylamino) ethyl methacrylate) (PMPC-PDPA) into membranes is tuned using pH and temperature. We report evolution from disk micelles, to vesicles, to high-genus vesicles (vesicles with many holes), where each passage is controlled by pH switch or temperature. We show that the process can be rationalized, adapting membrane physics theories to disclose scaling principles that allow the estimation of minimal radius of vesiculation as well as chain entanglement and coupling. This approach allows us to generate nanoscale vesicles with genus from 0 to 70, which have been very elusive and difficult to control so far.

Synthesis and Nano-object Assembly of Biomimetic Block Copolymers for Catalytic Silver Nanoparticles

Biomimetic ABC triblock copolymers of poly[2-(methacryloyloxy)ethyl phosphorylcholine]- b-poly[2-(dimethylamino)ethyl methacrylate]- b-poly(2-hydroxypropyl methacrylate) (PMPC- b-PDMA- b-PHPMA) were synthesized by RAFT aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) in the presence of a PMPC- b-PDMA macromolecular chain transfer agent (macro-CTA). This ABC triblock copolymer deploys well-known biocompatible PMPC and PDMA for the coordination of Ag+ ions to form silver nanoparticles in situ on reduction, and PHPMA for assembling (core) in water. The synthesis of PMPC- b-PDMA- b-PHPMA starts when both the reactive steric stabilizer of PMPC25- b-PDMA4 macro-CTA and HPMA monomer are dissolved in water. The growing PHPMA is not soluble in water and begins to assemble based on three-layer onion micelles, in which the outer and inner shells are PMPC and PDMA, respectively. In the synthesis of PMPC25- b-PDMA4- b-PHPMA z at a constant 25% (w/w) solids concentration, the resultant assemblies change from spheres to worms to jellyfishes to vesicles when the targeted PHPMA chain length increases from 100mer to 400mer at full monomer conversion. Furthermore, in the synthesis of identical PMPC25- b-PDMA4- b-PHPMA400 copolymers, the assembly morphology can be controlled from vesicles to spheres through worms by varying the solids concentration in the polymerization mixture, decreasing from 25% (w/w) to 15% (w/w) at full monomer conversion. Thus, the final morphology can be tuned by the degree of polymerization of HPMA and the solids concentration in the polymerization mixture. Using the resultant three PMPC25- b-PDMA4- b-PHPMA400 assemblies as scaffolds, Ag(0) nanoparticles (Ag-NPs) are obtained through in situ reduction of AgNO3 facilitated by electrostatic interactions between the Ag+ ions and PDMA moieties. The resultant Ag-NPs loaded in the assemblies exhibit excellent stability, dispersibility, and activity of catalyst for the reduction of p-nitrophenol. The order of rate constants for the reduction using Ag-NPs loaded in the assemblies is worms > vesicles > spheres, which corresponds to the order of the surface areas of the assemblies of PMPC25- b-PDMA4- b-PHPMA400. These results can be achieved thanks to the kinetically frozen PMPC25- b-PDMA4- b-PHPMA400 assemblies with identical compositions.

Zwitterionic poly(2-(methacryloyloxy) ethyl phosphorylcholine) coated mesoporous silica particles and doping with magnetic nanoparticles

Poly(2(methacryloyloxy) ethyl phosphorylcholine) (PMPC) a zwitterionic biopolymer has been used to prepare hybrid inorganic/organic/inorganic tri-layered magnetic composite particles. Mesoporous SiO2 particles of average diameter 284.8 nm are first prepared by sol-gel technique in presence of cetyltrimethylammonium bromride (CTAB) as template to generate porosity. The surface of mesoporous SiO2 particles is then functionalized to introduce vinyl functionality using silane coupling agent, 3-(trimethoxysilyl) propyl methacrylate (MPS). Finally grafting of MPC is carried out on the surface of mesoporous SiO2 particles by carrying out seeded copolymerization in presence of monomethoxy-capped poly(ethylene glycol) methacrylate (PEGMA) as a reactive steric stabilizer and ethylene glycol dimethacrylate (EGDMA) as a cross-linker. The prepared composite polymer particles named as SiO2/P(MPC-PEGMA-EGDMA) are finally doped with magnetic iron oxide nanoparticles (Fe3O4) via simultaneous in situ precipitation of Fe2+ and Fe3+ from alkali solution. The final composite particles possessed moderate paramagnetic property having magnetic susceptibility (2.22 × 10−5) which is just one order less than that of reference Fe3O4 nanoparticles (1.00 × 10-4). A comparative adsorption behaviour of biomolecules suggested that surface of SiO2/P(MPC-PEGMA-EGDMA) composite particles resist protein adhesion whereas after doping with Fe3O4 nanoparticles the surface has tendency to adsorb proteins.

Platinum(IV) complex-based two-in-one polyprodrug for a combinatorial chemo-photodynamic therapy

A combinatorial therapy that utilizes two or more therapeutic modalities is more effective in overcoming the limitations than each individual method used alone. Despite great advances have been achieved, the combination of chemotherapy and photodynamic therapy (PDT) still cannot satisfy the clinic requirements as the antitumor efficacy could be severely affected by tumor-associated hypoxia. Herein, for the first time, we reported a platinum(IV) complex-based polyprodrug that can in situ generate the highly toxic platinum(II) species as chemotherapeutics and simultaneously induce a high level of reactive oxygen species (ROS) in a PDT-like process without the use of photosensitizer and consumption of oxygen. By in situ polymerizing the platinum(IV) complex-based prodrug monomer (PPM) and 2-methacryloyloxy ethyl phosphorylcholine (MPC), nanosized hydrogel-like polyprodrug could be synthesized. Upon being exposed to light, Pt(IV) moieties in this photoactivable polyprodrug were reduced to generate Pt(II) species. At the meantime, a high level of ROS was generated without the presence of endogenous oxygen, which was confirmed by electron spin resonance (ESR) and fluorescence probes. With the unique nanosized architecture and photoresponsive feature, the as-synthesized polyprodrug exhibited the advantages of sustained drug release, long-term circulation, preferable tumor accumulation, and reversing drug resistance by downregulating the expression of multidrug resistance-associated protein 1 (MRP1) in the anticancer treatment.

Anticoagulant Properties of Poly(sodium 2-(acrylamido)-2-methylpropanesulfonate)-Based Di- and Triblock Polymers.

Di- and triblock copolymers with low dispersity of molecular weight were synthesized using radical addition-fragmentation chain transfer polymerization. The copolymers contained anionic poly(sodium 2-acrylamido-2-methylpropanesulfonate) (PAMPS) block as an anticoagulant component. The block added to lower the toxicity was either poly(ethylene glycol) (PEG) or poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC). The polymers prolonged clotting times both in vitro and in vivo. The influence of the polymer architecture and composition on the efficacy of anticoagulation and safety parameters was evaluated. The polymer with the optimal safety/efficacy profile was PEG47- b-PAMPS108, i.e., a block copolymer with the degrees of polymerization of PEG and PAMPS blocks equal to 47 and 108, respectively. The anticoagulant action of copolymers is probably mediated by antithrombin, but it differs from that of unfractionated heparin. PEG47- b-PAMPS108 also inhibited platelet aggregation in vitro and increased the prostacyclin production but had no antiplatelet properties in vivo. PEG47- b-PAMPS108 anticoagulant activity can be efficiently reversed with a copolymer of PEG and poly((3-(methacryloylamino)propyl)trimethylammonium chloride) (PMAPTAC) (PEG41- b-PMAPTAC53, HBC), which may be attributed to the formation of polyelectrolyte complexes with PEG shells without anticoagulant properties.

Tuned Surface and Mechanical Properties of Polymeric Film Prepared by Random Copolymers Consisting of Methacrylate‐POSS and 2‐(Methacryloyloxy)ethyl Phosphorylcholine

AbstractPoly(2‐(methacryloyloxy)ethyl phosphorylcholine) (PMPC) is known as a biocompatible polymers. Copolymerization of 2‐(methacryloyloxy)ethyl phosphorylcholine (MPC) and hydrophobic monomers is a general approach that gives bioinert functions to solid materials via the surface coating. However, due to the amorphous nature and super hydrophilicity of the MPC‐based copolymers, both the surface and the mechanical properties are not controlled for biomedical applications. Here, the modulated mechanical property and the surface wettability of the MPC‐based copolymers are shown by using a polyhedral oligomeric silsesquioxane (POSS) methacrylate. MPC is copolymerized with POSS methacrylates bearing different vertex groups of ethyl (C2H5), hexayl (C6H13), and octayl (C8H17) via radical polymerization. It is found that only the C2H5‐POSS induces the increased mechanical strength, low surface wettability, and cellular attachment, suggesting that the C2H5‐POSS moiety restricts the motion of PMPC chain. The finding is anticipated to be tuned for both surface and bulk functions of PMPC for biomedical applications.

Highly stable, electrostatically attractive silicone nanoemulsions produced by interfacial assembly of amphiphilic triblock copolymers.

This article presents a useful and promising approach for fabricating extremely stable silicone oil nanoemulsions, whose liquid-liquid interface is structured with a thin film of amphiphilic triblock copolymers. For this, two types of amphiphilic triblock polymer, poly(2-methacryloyloxy ethyl phosphorylcholine)-block-poly(ε-caprolactone)-block-poly(2-methacryloyloxy ethyl phosphorylcholine) (PMPC-PCL-PMPC) and poly(2-aminoethyl methacrylate)-block-poly(ε-caprolactone)-block-poly(2-aminoethyl methacrylate) (PAMA-PCL-PAMA), were synthesized by atom transfer radical polymerization. Employing the phase separation technique was critical for the formation of thin polymer interfaces, of less than 10 nm, thus eventually producing structurally stable silicone oil nanoemulsions. The co-assembly of PAMA-PCL-PAMA with PMPC-PCL-PMPC enabled the patching of positive charges on the surface of the emulsion drops. We show that these charged silicone oil nanoemulsions could be used to form a multilayer emulsion thin film by layer-by-layer deposition. Finally, we experimentally demonstrate that the silicone oil nanoemulsions fabricated in this way were highly stable and had the ability to electrostatically interact with hair, which enabled complete coating of the hair surface with a layer of silicone oil.

Hydrophilic polymeric monoliths containing choline phosphate for separation science applications

In this research, a hydrophilic polymeric monolith containing choline phosphate (CP) was fabricated through the thermally initiated free-radical polymerization of 2-{2-(methacryloyloxy) ethyldimethylammonium}ethyl n-butyl phosphate (MBP) with ethylene dimethacrylate (EDMA) using isopropanol and tetrahydrofuran as the porogenic system. Excellent mechanical strength, permeability, stability and reproducibility were obtained on the optimized poly(MBP-co-EDMA) monolith. Column efficiency as high as 107,500 plates/m was achieved for the analysis of thiourea at a flow velocity of 0.2 mm/s on the monolith. Both hydrophilic and electrostatic interactions were observed for the retention of charged analytes on the poly(MBP-co-EDMA) monolith. It is worth noting that the resulting monolith exhibits higher selectivity and efficiency than the classical 2-(methacryloyloxy)ethyl phosphorylcholine functionalized polymeric monolith for the chromatographic separation of polar analytes. Also, the novel monolithic column was successfully applied to enrich N-glycopeptides from tryptic digest of human IgG. In a word, the versatile MBP functionalized polymeric monolith not only opens up interesting possibilities for reverse zwitterionic CP derivative-based polymeric materials in separation science, but also represents a promising hydrophilic interaction chromatography stationary phase.

Direct surface grafting of mesoporous silica nanoparticles with phospholipid choline-containing copolymers through chain transfer free radical polymerization and their controlled drug delivery

Mesoporous silica nanoparticles have attracted considerable research attention due to their various applications. Surface modification of these mesoporous silica nanoparticles with polymers not only can improve their water dispersity but can also endow several new functions, such as drug loading and delivery or targeting capability. In this work, we report a novel strategy for the direct surface grafting of phospholipid choline-containing copolymers onto Santa Barbara Amorphous-15 (SBA-15) through surface-initiated chain transfer free radical polymerization. The SBA-15 was synthesized by hydrolysis of tetraethoxysilane in the presence of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P123) under acidic synthetic conditions. Next, SBA-15 was subsequently modified with thiol groups by co-condensation with γ-mercaptopropyltrimethoxysilane to obtain SBA-15-SH. Finally, the copolymers were grafted on SBA-15-SH through chain transfer free radical polymerization using 2-methacryloyloxy ethyl phosphorylcholine (MPC) and itaconic acid (IA) as monomers. The SBA-15-based polymer composites (SBA-15-SH-poly(MPC-co-IA)) were used as matrices for controlled release of cisplatin (CDDP). The data from a series of characterization techniques indicated that the monomers were successfully grafted onto SBA-15. The resultant SBA-15-SH-poly(MPC-co-IA) composites showed many remarkable physicochemical properties, such as high water dispersity, desirable biocompatibility and high drug loading capacity. These features provide the SBA-15-SH-poly(MPC-co-IA) composites with considerable potential for biomedical applications.

Understanding the Oxidative Stability of Antifouling Polymer Brushes.

Poly(oligoethylene glycol methacrylate) (POEGMA) and zwitterionic polymer brushes have been widely used for constructing biocompatible or antifouling surfaces, and their oxidative stability is very important to the practical application. Herein, POEGMA, poly(sulfobetaine methacrylate) (PSBMA), poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC), and poly(carboxybetaine methacrylate) (PCBMA) were grafted on quartz crystal microbalance (QCM) chips via surface-initiated atom transfer radical polymerization (SI-ATRP). XPS and MS analyses demonstrate that the mass loss of these polymer brushes in oxidative environment is due to the scission of the polymer-anchoring segments. Molecular simulation further illustrates this mass loss mechanism should be always true for those polymer brushes anchored on different substrates. In situ QCM monitoring indicates that, compared with zwitterionic polymethacrylates, POEGMA brushes show the lowest mass loss rate mainly due to their cross-linked structures. This study sheds light on the contradictory reports about the oxidative stability of POEGMA and zwitterionic polymethacrylate brushes up to now, and highlights the important role of the polymer-anchoring segments playing in the oxidative stability of polymer brushes.

Complexes Covered with Phosphorylcholine Groups Prepared by Mixing Anionic Diblock Copolymers and Cationic Surfactants.

Anionic diblock copolymers (PmAn) composed of biocompatible polybetaine, poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC), and anionic poly(sodium 2-(acrylamido)-2-methylpropanesulfonate) (PAMPS) were synthesized via reversible addition-fragmentation chain transfer (RAFT) radical polymerization. Two types of diblock copolymers (P24A217 and P100A99) were prepared with different compositions. The PmAn/CTAB complexes were formed by a stoichiometrically charge-neutralized mixture of anionic PmAn and cationic cetyltrimethylammonium bromide (CTAB) micelles in water. The complexes prepared using P24A217 and P100A99 were vesicles and micelles, respectively, and were covered with hydrophilic PMPC shells. The complexes dissociated upon addition of NaCl because the complex was maintained through electrostatic interactions. The P24A217/CTAB vesicles could encapsulate uncharged hydrophilic guest molecules into the interior of the aqueous phase.

Surface grafting of zwitterionic polymers onto dye doped AIE-active luminescent silica nanoparticles through surface-initiated ATRP for biological imaging applications

Aggregation-induced emission (AIE) dyes have recently been intensively explored for biological imaging applications owing to their outstanding optical feature as compared with conventional organic dyes. The AIE-active luminescent silica nanoparticles (LSNPs) are expected to combine the advantages both of silica nanoparticles and AIE-active dyes. Although the AIE-active LSNPs have been prepared previously, surface modification of these AIE-active LSNPs with functional polymers has not been reported thus far. In this work, we reported a rather facile and general strategy for preparation of polymers functionalized AIE-active LSNPs through the surface-initiated atom transfer radical polymerization (ATRP). The AIE-active LSNPs were fabricated via direct encapsulation of AIE-active dye into silica nanoparticles through a non-covalent modified Stöber method. The ATRP initiator was subsequently immobilized onto these AIE-active LSNPs through amidation reaction between 3-aminopropyl-triethoxy-silane and 2-bromoisobutyryl bromide. Finally, the zwitterionic 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) was selected as model monomer and grafted onto MSNs through ATRP. The characterization results suggested that LSNPs can be successfully modified with poly(MPC) through surface-initiated ATRP. The biological evaluation results demonstrated that the final SNPs-AIE-pMPC composites possess low cytotoxicity, desirable optical properties and great potential for biological imaging. Taken together, we demonstrated that AIE-active LSNPs can be fabricated and surface modified with functional polymers to endow novel functions and better performance for biomedical applications. More importantly, this strategy developed in this work could also be extended for fabrication of many other LSNPs polymer composites owing to the good monomer adoptability of ATRP.

A novel functionalization method for carbon nanotubes to repel ox-LDL in treatments after stent placement

Carbon nanotubes (CNT) can be chemically modified by doping or functionalization to change the chemical and surface properties. These characteristic makes to CNT candidates for multiple applications including medical field in cardiovascular area. A novel method to CNT functionalization by formation of two compounds: α-bromoacid and the organic compound 2-(methacryloyloxy) ethyl phosphorylcholine (MPC), will be discussed in this article. According to results, CNT are suggested like candidates to repel oxidized low-density lipoproteins (ox-LDL) to prevent restenosis. The electronegative character on surface of functionalized CNT (F-CNT) is shown by wettability analysis observing a repellent behaviour in contact with ox-LDL after functionalization route. Here we analyse the toxicity of CNT and F-CNT on HepG2 cell line and find no damage to the cell membrane of HepG2 cells in concentration at doses below 1mg/ml.

Polyion Complex Vesicles with Solvated Phosphobetaine Shells Formed from Oppositely Charged Diblock Copolymers.

Diblock copolymers consisting of a hydrophilic poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) block and either a cationic or anionic block were prepared from (3-(methacrylamido)propyl)trimethylammonium chloride (MAPTAC) or sodium 2-(acrylamido)-2-methylpropanesulfonate (AMPS). Polymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) radical polymerization using a PMPC macro-chain transfer agent. The degree of polymerization for PMPC, cationic PMAPTAC, and anionic PAMPS blocks was 20, 190, and 196, respectively. Combining two solutions of oppositely charged diblock copolymers, PMPC-b-PMAPTAC and PMPC-b-PAMPS, led to the spontaneous formation of polyion complex vesicles (PICsomes). The PICsomes were characterized using 1H NMR, static abd dynamic light scattering, transmittance electron microscopy (TEM), and atomic force microscopy. Maximum hydrodynamic radius (Rh) for the PICsome was observed at a neutral charge balance of the cationic and anionic diblock copolymers. The Rh value and aggregation number (Nagg) of PICsomes in 0.1 M NaCl was 78.0 nm and 7770, respectively. A spherical hollow vesicle structure was observed in TEM images. The hydrodynamic size of the PICsomes increased with concentration of the diblock copolymer solutions before mixing. Thus, the size of the PICsomes can be controlled by selecting an appropriate preparation method.

Thermal sensitivity and protein anti-adsorption of hydroxypropyl cellulose-g- poly(2-(methacryloyloxy) ethyl phosphorylcholine)

Zwitterionic graft copolymers, hydroxypropyl cellulose graft poly(2-(methacryloyloxy) ethyl phosphorylcholine) (HPC-g-PMPC) with well-defined architecture were synthesized by atom transfer radical polymerization (ATRP). The self-assembly behaviors and thermal sensitivity of HPC-g-PMPC copolymers and their correlations with graft density and side chain length were investigated in details. HPC-g-PMPC copolymers can self-assemble into spherical aggregate structure above the critical aggregation concentration (CAC) at room temperature. Meanwhile, the size of the aggregates mainly depended on the graft density. The obtained aggregates were thermal sensitive and their low critical solution temperature (LCST) was efficiently regulated by varying the graft density. Above the LCST, the aggregates were transferred into aggregates with core-shell structure, in which the HPC rich core was stabilized by the PMPC rich shell. The interaction between the HPC-g-PMPC aggregates and BSA was investigated. The results indicated that the anti-adsorption of BSA on the aggregates surface depended on the length and graft density of the PMPC zwitterionic side chains.

Antimicrobial Graft Copolymer Gels.

In view of the growing worldwide rise in microbial resistance, there is considerable interest in designing new antimicrobial copolymers. The aim of the current study was to investigate the relationship between antimicrobial activity and copolymer composition/architecture to gain a better understanding of their mechanism of action. Specifically, the antibacterial activity of several copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and 2-hydroxypropyl methacrylate (HPMA) toward Staphylococcus aureus was examined. Both block and graft copolymers were synthesized using either atom transfer radical polymerization or reversible addition-fragmentation chain transfer polymerization and characterized via (1)H NMR, gel permeation chromatography, rheology, and surface tensiometry. Antimicrobial activity was assessed using a range of well-known assays, including direct contact, live/dead staining, and the release of lactate dehydrogenase (LDH), while transmission electron microscopy was used to study the morphology of the bacteria before and after the addition of various copolymers. As expected, PMPC homopolymer was biocompatible but possessed no discernible antimicrobial activity. PMPC-based graft copolymers comprising PHPMA side chains (i.e. PMPC-g-PHPMA) significantly reduced both bacterial growth and viability. In contrast, a PMPC-PHPMA diblock copolymer comprising a PMPC stabilizer block and a hydrophobic core-forming PHPMA block did not exhibit any antimicrobial activity, although it did form a biocompatible worm gel. Surface tensiometry studies and LDH release assays suggest that the PMPC-g-PHPMA graft copolymer exhibits surfactant-like activity. Thus, the observed antimicrobial activity is likely to be the result of the weakly hydrophobic PHPMA chains penetrating (and hence rupturing) the bacterial membrane.

Rescue of mitochondrial function in parkin-mutant fibroblasts using drug loaded PMPC-PDPA polymersomes and tubular polymersomes

Mutations in parkin cause autosomal recessive Parkinsonism and mitochondrial defects. A recent drug screen identified a class of steroid-like hydrophobic compounds able to rescue mitochondrial function in parkin-mutant fibroblasts. Whilst these possess therapeutic potential, the size and high hydrophobicity of some may limit their ability to penetrate the blood-brain barrier from systemic circulation, something that could be improved by novel drug formulations. In the present study, the steroid-like compounds Ursolic Acid (UA) and Ursocholanic Acid (UCA) were successfully encapsulated within nanoscopic polymersomes formed by poly(2-(methacryloyloxy)ethyl phosphorylcholine)–poly(2-di-isopropylamino)ethyl methacrylate) (PMPC-PDPA) and separated into spherical and tubular morphologies to assess the effects of nanoparticle mediated delivery on drug efficacy. Following incubation with either morphology, parkin-mutant fibroblasts demonstrated time and concentration dependent increases in intracellular ATP levels, resembling those resulting from treatment with nascent UA and UCA formulated in 0.1% DMSO, as used in the original drug screen. Empty PMPC-PDPA polymersomes did not alter physiological measures related to mitochondrial function or induce cytotoxicity. In combination with other techniques such as ligand functionalisation, PMPC-PDPA nanoparticles of well-defined morphology may prove a promising platform for tailoring the pharmacokinetic profile and organ specific bio-distribution of highly hydrophobic compounds.