Amphiphilic Copolymer Brush Research Articles

PH-sensitive amphiphilic copolymer brush Chol-g-P(HEMA-co-DEAEMA)-b-PPEGMA: synthesis and self-assembled micelles for controlled anti-cancer drug release

A novel pH-sensitive amphiphilic copolymer Chol-g-P(HEMA-co-DEAEMA)-b-PPEGMA and its micelles were developed as a promising anti-cancer drug carrier.

Preparation and controlled release performances of drug loaded micelles self-assembled from pH-sensitive amphiphilic copolymer brushes

Preparation and controlled release performances of drug loaded micelles self-assembled from pH-sensitive amphiphilic copolymer brushes

Synthesis of Amphiphilic Poly(ethylene oxide-co -glycidol)-graft -polyacrylonitrile Brush Copolymers and their Self-assembly in Aqueous Media

An amphiphilic copolymer brush poly(ethylene oxide-co-glycidol)-graft-polyacrylonitrile [poly(EO-co-Gly)-g-PAN], is successfully prepared for the first time by a combination of anionic polymerization and redox free radical polymerization. The final products and intermediates are characterized by NMR and GPC. Aggregates made from the brush copolymers, poly(EO-co-Gly)-g-PAN, with a long hydrophobic graft length in water are studied by TEM and DLS. The effects of hydrophobic graft length and water content on the morphologies are discussed. Some rare morphologies of aggregates are observed, such as lamellae, bicontinuous networks, bowls or nanosheets, and large compound rods with a brittleness that can be ascribed to the orientation of high content semi-crystalline PAN segments.

Amphiphilic copolymer brush with random pH-sensitive/hydrophobic structure: synthesis and self-assembled micelles for sustained drug delivery

A random hydrophobic/pH-sensitive copolymer brush poly(polylactide methacrylate-co-methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether methacrylate) [P(PLAMA-co-MAA)-b-PPEGMA] and its self-assembled micelles were developed for oral administration of hydrophobic drugs. The polymer was synthesized by the combination of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and ring opening polymerization (ROP). The CMC of P(PLAMA-co-MAA)-b-PPEGMA in aqueous solution was extremely low (about 1.5 mg L−1). The self-assembled blank and drug-loaded micelles were spherical in morphology and had an average size of 160–220 nm, determined by DLS and SEM. Ibuprofen (IBU) was selected as the model drug and encapsulated into the core of micelles via a dialysis method. The in vitro release behavior of IBU from these micelles was pH-dependent. In simulated gastric fluid (SGF, pH 1.2), the cumulative release of IBU was less than 25% of the initial drug content over 24 h, suggesting that the drug can be well protected from the harsh environment in stomach. While in simulated intestinal fluid (SIF, pH 7.4), the ionization of carboxyl groups of MAA contributed to the swelling of the micelle structure, which could accelerate the IBU release from the micelles. 35–45% of IBU was released in 8 h, 60% in 24 h, and 100% after 56 h for P(PLAMA6.3k-co-MAA3k)-b-PPEGMA4k micelles, and it was 50% in 2 h, 90% in 10 h, and 100% after 14 h for P(PLAMA6.3k-co-MAA4.5k)-b-PPEGMA4k micelles with an increased content of MAA. All the results indicate that the pH-sensitive P(PLAMA-co-MAA)-b-PPEGMA micelles may be a potential oral drug delivery carrier for hydrophobic drugs with sustained release.

Synthesis of pH-Sensitive Amphiphilic Copolymer Brush by the Combination of ARGET ATRP with ROP and Its Self-Assembly Behavior

A random hydrophobic/pH-sensitive copolymer brush poly(polylactide methacrylate-co- methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (P(PLAMA-co-MAA)-b- PPEGMA) was synthesized by the combination of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) with ring opening polymerization (ROP). The chemical structure, molecular weight and polydispersity index were characterized by nuclear magnetic resonance hydrogen spectrum ( 1 H NMR) and gel permeation chromatography (GPC). The reaction conditions of polymerization were optimized and polymer products with controllable molecular weight and narrow distribution were ob- tained. The self-assembly behavior (micelle size, morphology and pH-sensitive properties) of the polymer brush was investigated by dynamic light scattering (DLS) and scanning electron microscopy (SEM). The P(PLAMA-co-MAA)-b-PPEGMA self-assembled micelles were sphere in morphology and with an uniform

PH-Sensitive Micelles Self-Assembled from Amphiphilic Copolymer Brush for Delivery of Poorly Water-Soluble Drugs

A novel pH-sensitive amphiphilic copolymer brush poly(methyl methacrylate-co-methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether monomethacrylate) [P(MMA-co-MAA)-b-PPEGMA] was defined and synthesized by atom transfer radical polymerization (ATRP) technique. The molecular structures and characteristics of this copolymer and its precursors were confirmed by (1)H NMR, FT-IR, and GPC. The CMC of P(MMA-co-MAA)-b-PPEGMA in aqueous medium was determined to be 1-4 mg/L. This copolymer could self-assemble into micelles in aqueous solution with an average size of 120-250 nm determined by DLS. The morphologies of the micelles were found to be spherical by SEM and TEM. Ibuprofen (IBU), a poorly water-soluble drug, was selected as the model drug and wrapped into the core of micelles via dialysis method. Drug entrapment efficiency reached to 90%. The in vitro release behavior of IBU from these micelles was pH-dependent. The cumulative release percent of IBU was less than 20% of the initial drug content in simulated gastric fluid (SGF, pH 1.2) over 12 h, but 90% was released in simulated intestinal fluid (SIF, pH 7.4) within 6 h. The release profiles showed that the P(MMA-co-MAA)-b-PPEGMA micelles could inhibit the premature burst drug release under the intestinal conditions. All the results indicate that the P(MMA-co-MAA)-b-PPEGMA micelle may be a potential oral drug delivery carrier for poorly water-soluble drugs.

Stereoregular polyacrylamide and its copolymer brushes: Preparation and surface characters

Two kinds of polymer brushes, the single one with stereospecific polyacrylamide (PAAM) chains and the dual-component one with random poly(methyl methacrylate) (PMMA) segments grafting from stereospecific PAAM chains, were prepared on silicon wafer for the first time by combining the immobilization of initiator and the stereospecific living radical in situ polymerization. With the addition of the Lewis acid AlCl 3 into the polymerization system, the PAAM brushes obtained exhibited an increased stereospecificity as well as a decreased hydrophilicity, which might attribute to the reduced thickness of PAAM brushes on the silicon wafer and the handicap of the free rotation of the stereospecific molecular chain. The smoother surface morphology of the stereospecific PAAM brushes shown in AFM images was in good agreement with the experimental data of water contact angle. Also, block amphiphilic copolymer brushes were prepared with the stereospecific PAAM formed first on silicon wafer as the anchored-initiator and revealed a novel surface self-assembly behavior after being treated with different solvent such as toluene or water. The stereospecificity of PAAM chains in the polymer brushes could be modulated by adjusting reaction conditions according to the requirement of applications for surface hydrophilicity.

Synthesis of amphiphilic copolymer brushes: Poly(ethylene oxide)‐graft‐polystyrene

AbstractA well‐defined amphiphilic copolymer brush with poly(ethylene oxide) as the main chain and polystyrene as the side chain was successfully prepared by a combination of anionic polymerization and atom transfer radical polymerization (ATRP). The glycidol was first protected by ethyl vinyl ether to form 2,3‐epoxypropyl‐1‐ethoxyethyl ether and then copolymerized with ethylene oxide by the initiation of a mixture of diphenylmethylpotassium and triethylene glycol to give the well‐defined polymer poly(ethylene oxide‐co‐2,3‐epoxypropyl‐1‐ethoxyethyl ether); the latter was hydrolyzed under acidic conditions, and then the recovered copolymer of ethylene oxide and glycidol {poly(ethylene oxide‐co‐glycidol) [poly(EO‐co‐Gly)]} with multiple pending hydroxymethyl groups was esterified with 2‐bromoisobutyryl bromide to produce the macro‐ATRP initiator [poly(EO‐co‐Gly)(ATRP). The latter was used to initiate the polymerization of styrene to form the amphiphilic copolymer brushes. The object products and intermediates were characterized with 1H NMR, matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry, Fourier transform infrared, and size exclusion chromatography in detail. In all cases, the molecular weight distribution of the copolymer brushes was rather narrow (weight‐average molecular weight/number‐average molecular weight < 1.2), and the linear dependence of ln[M0]/[M] (where [M0] is the initial monomer concentration and [M] is the monomer concentration at a certain time) on time demonstrated that the styrene polymerization was well controlled. This method has universal significance for the preparation of copolymer brushes with hydrophilic poly(ethylene oxide) as the main chain. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4361–4371, 2006

Aggregation behavior of proto-type amphiphilic copolymer brushes in aqueous solution

It is well known that comb copolymers with densely grafted side chains in a good solvent can adopt a worm-like cylindrical brush conformation, in which the side chains are stretched in the direction normal to the backbone owing to the excluded volume interaction. Polymerizations of macromonomers provide regular multi-branched polymers with dense branching. Since both degree of polymerization and the length of branches are varied, poly(macromonomer)s, often so-called “polymer brushes,” are interesting models for the study of the branched polymers [1–9]. We have reported the synthesis and dilutesolution properties of poly(diblock macromonomer)s: polystyrene-block-polyisoprene (PS-block-PI) [10] and PS-block-poly(2-vinylpyridine) (P2VP) diblock poly (macromonomer)s [11]. These types of poly(diblock macromonomer)s have the advantage of controlling the stiffness of the main chain parts by crosslinking inner PI or P2VP blocks. Free-radical copolymerization of binary macromonomers will form copolymers with not only combshaped but also hetero-armed structures. In this preparation process, the relevant copolymerization parameters are very important in determining the branch distribution in the resulting comb-shaped copolymers. Free-radical copolymerizations of binary vinylbenzylterminated PS and PI macromonomers were carried out in benzene, varying the molecular weight of the macromonomers [12]. The reactivity ratios of these systems were close to an azeotropic copolymerization, in the case of the same degree of polymerization (DP) for binary macromonomers. Subsequently, free-radical copolymerizations of vinylbenzyl-terminated PS (PSVM; M1) with maleate-terminated poly(ethylene oxide) (PEO-MA; M2) were carried out in benzene, in order to achieve alternative reactivity [13]. The reactivity ratios (r1 = 0.765 and r2 = 0.064) obtained for such binary macromonomer systems were different from the corresponding model system of styrene and maleic acid ethyl ester (r1 = 0.13 and r2 = 0.035) due to phase separation. More recently, free-radical copolymerizations of PS-VM (M1) with methacryloyl-terminated PEO (PEO-MC; M2) were carried out under various copolymerization conditions [14]. As a result, the reactivity ratios (r1 = 0.25 and r2 = 0.02) obtained for the binary copolymerization of PS-VM with PEO-MC/tin tetrachloride (SnCl4) complex showed strong alternation (Scheme 1). It was suggested the alternation results from homopolymerization of 1 : 1 complexes formed Scheme 1