Novel antifouling oligo(ethylene glycol) methacrylate particles via surfactant-free emulsion polymerization

The use of particle formulations with antifouling surface properties attracts increasing interest in several biotechnological applications. Majority of these studies utilize a poly(ethylene glycol) coating to render the corresponding surface nonrecognizable to biological macromolecules. Herein, we report a simple way to prepare novel antifouling colloids composed of oligo(ethylene glycol) backbones via surfactant-free emulsion polymerization. Monodisperse cross-linked poly(ethylene glycol) ethyl ether methacrylate particles were characterized by dynamic light scattering and transmission electron microscopy. The effects of monomer, cross-linker and initiator on particle characteristics were investigated. More importantly, a prominent blockage of bovine serum albumin adsorption was obtained for the poly(ethylene glycol)-based sub-micron (~200 nm) particles when compared with similar-sized poly(methyl methacrylate) counterparts.     

Stimuli‐responsive cationic terpolymers by RAFT polymerization: Synthesis,characterization, and protein interaction studies

The controlled synthesis and characterization of a range of stimuli responsive cationic terpolymers containing varying amounts of N‐isopropylacrylamide (NIPAM), 3‐(methylacryloylamino)propyl trimethylammonium chloride (MAPTAC), and poly(ethylene glycol)monomethyl methacrylate (PEGMA) is presented. The terpolymers were synthesized using reversible addition‐fragmentation chain transfer (RAFT) polymerization. Compositions of the terpolymers determined using ¹H NMR were in close agreement to the theoretical values determined from the monomer feed ratios. GPC‐MALLS was used to analyze the molecular weight characteristics of the polymers, which were found to have low polydispersities (M_w/M_n 1.1–1.4). The phase transitions were studied as a function of PEGMA and NIPAM content using temperature controlled ¹H NMR and turbidity measurements (UV‐Vis). The relationship between thermal stability and the comonomer ratio of the polymers was measured using thermogravimetric analysis (TGA). Protein interaction studies were performed to determine the suitability of the polymers for biological applications. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4021–4029, 2008     

Synthesis,self‐assembly,fluorescence, and thermosensitive properties of star‐shaped amphiphilic copolymers with porphyrin core

Star‐shaped amphiphilic poly(ε‐caprolactone)‐block‐poly(oligo(ethylene glycol) methyl ether methacrylate) with porphyrin core (SPPCL‐b‐POEGMA) was synthesized by combination of ring‐opening polymerization (ROP) and atom transfer radical polymerization (ATRP). Star‐shaped PCL with porphyrin core (SPPCL) was prepared by bulk polymerization of ε‐caprolactone (CL) with tetrahydroxyethyl‐terminated porphyrin initiator and tin 2‐ethylexanote (Sn(Oct)₂) catalyst. SPPCL was converted into SPPCLBr macroinitiator with 2‐bromoisobutyryl bromide. Star‐shaped SPPCL‐b‐POEGMA was obtained via ATRP of oligo(ethylene glycol) methyl ether methacrylate (OEGMA). SPPCL‐b‐POEGMA can easily self‐assemble into micelles in aqueous solution via dialysis method. The formation of micellar aggregates were confirmed by critical micelle formation concentration, dynamic light scattering, and transmission electron microscopy. The micelles also exhibit property of temperature‐induced drug release and the lower critical solution temperature (LCST) was 60.6 °C. Furthermore, SPPCL‐b‐POEGMA micelles can reversibly swell and shrink in response to external temperature. In addition, SPPCL‐b‐POEGMA can present obvious fluorescence. Finally, the controlled drug release of copolymer micelles can be achieved by the change of temperatures. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Backfilling‐Free Strategy for Biopatterning on Intrinsically Dual‐Functionalized Poly[2‐Aminoethyl Methacrylate‐co‐Oligo(Ethylene Glycol) Methacrylate] Films

We demonstrated protein and cellular patterning with a soft lithography technique using poly[2‐aminoethyl methacrylate‐co‐oligo(ethylene glycol) methacrylate] films on gold surfaces without employing a backfilling process. The backfilling process plays an important role in successfully generating biopatterns; however, it has potential disadvantages in several interesting research and technical applications. To overcome the issue, a copolymer system having highly reactive functional groups and bioinert properties was introduced through a surface‐initiated controlled radical polymerization with 2‐aminoethyl methacrylate hydrochloride (AMA) and oligo(ethylene glycol) methacrylate (OEGMA). The prepared poly(AMA‐co‐OEGMA) film was fully characterized, and among the films having different thicknesses, the 35 nm‐thick biotinylated, poly(AMA‐co‐OEGMA) film exhibited an optimum performance, such as the lowest nonspecific adsorption and the highest specific binding capability toward proteins.     

Facile synthesis of ABCDE‐type H‐shaped quintopolymers by combination of ATRP,ROP, and click chemistry and their potential applications as drug carriers

A facile approach to synthesis of ABCDE‐type H‐shaped quintopolymer comprising polystyrene (PSt, C) main chain and poly(ethylene glycol) (PEG, A), poly(ε‐caprolactone) (PCL, B), poly(L ‐lactide) (PLLA, D), and poly(acrylic acid) (PAA, E) side chains was described, and physicochemical properties and potential applications as drug carriers of copolymers obtained were investigated. Azide‐alkyne cycloaddition reaction and hydrolysis were used to synthesize well‐defined H‐shaped quintopolymer. Cytotoxicity studies revealed H‐shaped copolymer aggregates were nontoxic and biocompatible, and drug loading and release properties were affected by macromolecular architecture, chemical composition, and pH value. The release rate of doxorubicin from copolymer aggregates at pH 7.4 was decreased in the order PAA‐b‐PLLA > H‐shaped copolymer > PEG‐PCL‐PSt star, and the release kinetics at lower pH was faster. The H‐shaped copolymer aggregates have a potential as controlled delivery vehicles due to their excellent storage stability, satisfactory drug loading capacity, and pH‐sensitive release rate of doxorubicin. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and characterization of thermoresponsive poly(ethylene glycol)‐based hydrogels and their magnetic nanocomposites

Temperature‐responsive hydrogels are one of the most widely studied types of stimuli‐responsive hydrogel systems. Their ability to transition between their swollen and collapsed states makes them attractive for controlled drug delivery, microfluidic devices, and biosensor applications. Recent work has shown that poly(ethylene glycol) (PEG) methacrylate polymers are temperature‐responsive and exhibit a wide range of lower critical solution temperatures based on the length of ethylene glycol units in the macromer chain. The addition of iron oxide nanoparticles into the hydrogel matrix can provide the ability to remotely heat the gels upon exposure to an alternating magnetic field (AMF). In this work, diethylene glycol (n = 2) methyl ether methacrylate and PEG (n = 4.5) methyl ether methacrylate copolymers were polymerized into hydrogels with 5 mol % PEG 600 (n = 13.6) dimethacrylate as the crosslinker along with 5 wt % iron oxide nanoparticles. Volumetric swelling studies were completed from 22 to 80 °C and confirmed the temperature‐responsive nature of the hydrogel systems. The ability of the gels to collapse in response to rapid temperature changes when exposed to an AMF was demonstrated showing their potential use in biomedical applications such as controlled drug delivery and hyperthermia therapy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3229–3235, 2010     

Thermoresponsive PNIPAM/silica nanoparticles by direct photopolymerization in aqueous media

This article presents a simple and facile method to fabricate thermoresponsive polymer‐grafted silica particles by direct surface‐initiated photopolymerization of N‐isopropylacrylamide (NIPAM). This method is based on silica particles bearing thiol functionalities, which are transformed into thiyl radicals by irradiation with UV light to initiate the polymerization of NIPAM in aqueous media at room temperature. The photopolymerization of NIPAM could be applied to smaller thiol‐functionalized particles (～48 nm) as well as to larger particles (～692 nm). Hollow poly(NIPAM) capsules could be formed after etching away the silica cores from the composite particles. It is possible to produce tailor‐made composite particles or capsules for particular applications by extending this approach to other vinyl monomers. © 2015 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 2015 , 53, 1260–1267     

Synthesis of amphiphilic polyacetal by polycondensation of aldehyde and polyethylene glycol as an acid‐labile polymer for controlled release of aldehyde

A new acid‐labile polymer having acetal moieties in the main chain was synthesized by polycondensation of poly (ethylene glycol) (PEG) and lilial, an aldehyde widely used in fragrance applications. The hydrophobicity of the resulting acetal moiety and the hydrophilicity of the PEG chain allowed the polyacetal to exhibit amphiphilicity. The polyacetal derived from PEG having weight average molecular weight (M_w) of 1000 (PEG1000) was soluble in water and self‐associated to form associates in water. The polyacetals were hydrolyzed in acidic aqueous solutions to release hydrophobic lilial from the systems. The release rate of aldehyde from the polyacetal derived from PEG1000 was higher than that from the polyacetal derived from PEG having M_w of 400 (PEG400). These results supported that the release rate of lilial can be controlled by the chain length of PEG, on which hydrophilicity of polyacetal depends. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis,characterization, and properties of tunable thermosensitive amphiphilic dendrimer‐star copolymers with Y‐shaped arms

Novel and well‐defined amphiphilic dendrimer‐star copolymer poly(ε‐caprolactone)‐block‐(poly(2‐(2‐methoxyethoxy)ethylmethacrylate‐co‐oligo(ethylene glycol) methacrylate))₂ with Y‐shaped arms were synthesized by the combination of ring‐opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The investigation of thermal properties and the analysis of crystalline morphology indicate that the high‐branched structure of dendrimer‐star copolymers with Y‐shaped arms and the presence of amorphous P(MEO₂MA‐co‐OEGMA) segments together led to the complete destruction of crystallinity of the PCL segments in the dendrimer‐star copolymer. In addition, the hydrophilicity–hydrophobicity transition of the dendrimer‐star copolymer film can be achieved by altering the external temperatures. The amphiphilic copolymers can self‐assemble into spherical nanomicelles in water. Because the lower critical solution temperature of the copolymers can be adjusted by varying the ratio of MEO₂MA and OEGMA, the tunable thermosensitive properties can be observed by transmittance, dynamic laser light scattering, and transmission electron microscopy (TEM). The release rate of model drug chlorambucil from the micelles can be effectively controlled by changing the external temperatures, which indicates that these unique high‐branched amphiphilic copolymers have the potential applications in biomedical field. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis of an esterase‐sensitive degradable polyester as facile drug carrier for cancer therapy

Polyethylene glycol (PEG) is widely used as a carrier to improve the pharmaceutical properties of drugs with low molecular weight. However, PEG has few functional groups (usually two) for drug conjugation and the resulting low drug content (1–2%) has hampered its clinical applications. For this study, we synthesized biodegradable poly(ethylene glycol‐co‐anhydride). This polyester‐based polymer possesses multiple carboxylic acid groups that can be used as facile drug carriers. Two anticancer drugs, camptothecin (CPT) and doxorubicin (DOX) were loaded into the carrier and their releasing properties and in vitro anticancer activities were studied. The polymer–drug conjugates exhibited esterase‐promoted degradation and drug release. Their cytotoxicity against the human ovarian cancer cell line SKOV‐3 was comparable to unconjugated drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 507–515     

RAFT cryopolymerizations of N,N‐dimethylacrylamide and N‐isopropylacrylamide in moderately frozen aqueous solution

Aqueous reversible addition‐fragmentation chain transfer (RAFT) cryopolymerizations of N,N‐dimethylacrylamide (DMA) and N‐isopropylacrylamide (NIPAM) with potassium persulfate/sodium ascorbate as redox initiators were performed at ?15 °C. For the homopolymerizations, water‐soluble chain transfer agents (CTAs) of 2‐(1‐carboxy‐1‐methylethyl‐sulfanylthiocarbonylsulfanyl)‐2‐methylpropionic acid and 2‐dodecylsulfanylthiocarbonylsulfanyl‐2‐methylpropionyl‐capped methoxy poly(ethylene glycol) were used. For the sequential block copolymerizations, the obtained trithiocarbonate‐functionalized polymers were used as macro‐CTAs. Although well‐defined homo and block polymers of DMA and NIPAM were synthesized and these RAFT cryopolymerizations were well controlled, their behavior depended on the monomers and CTAs. The polymerization kinetic and polymer structure were studied by proton nuclear magnetic resonance analysis and gel permeation chromatography measurement. Poly(N,N‐dimethylacrylamide)‐based cryogels crosslinked with reductively cleavable disulfide‐containing diacrylamide, N,N′‐bisacryloylcystamine, were synthesized via RAFT cryopolymerization. Scanning electron microscopy observation revealed that the porous structure of cryogels depended on the CTA used. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2009     

Composite polymer particles with stimuli-responsive surface properties and specific activity of adsorbed/released trypsin

Micron-sized monodispersed stimuli-responsive polys’ (PS)/poly(2-dimethylaminoethyl methacrylate-N-isopropyl acrylamide-ethylene glycol dimethacrylate) [P(DM-NIPAM-EGDM)] composite polymer particles were prepared by seeded copolymerisation of DM, NIPAM and EGDM with PS seed particles. Adsorption behaviour of trypsin suggested that composite particles surface has both temperature- and pH-responsive swelling–deswelling characteristics. The performance of composite polymer particles as a carrier for biomolecules in adsorption/release experiments was evaluated by measuring the specific activities of adsorbed trypsin as a function of temperature and pH.     

Understanding and preventing the formation of deformed polymer particles during synthesis by a seeded polymerization method

Uniformly sized porous polymer particles with different polarity namely poly(divinylbenzene), poly(vinyl acetate‐co‐divinylbenzene), poly(ethylene dimethacrylate), and poly (glycidyl methacrylate‐co‐ethylene dimethacrylate) were prepared in the micron‐size range by a seeded polymerization method. Parameters affecting the particle morphologies including monomer mixture content, porogen content, and polystyrene (PS) seed latexes were varied, and the morphologies of the resulting particles were investigated by scanning electron and confocal microscopy. The results obtained indicated that the particle shape depended dominantly on the molecular weight of the PS seed template. Deformed particles, including collapsed spheres and spheres with holes were obtained when high molecular weight PS seeds were used, whereas well‐defined polymer particles were produced easily by using low molecular weight seeds. The use of 1,1‐diphenylethylene as a chain terminator during seed polymerization is proposed in this work as an efficient method to lower molecular weight of PS in seed particles while keeping seed size small. This low molecular weight seed template retained its spherical geometry after swelling and polymerization with different second stage monomers. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis and micellization of new biodegradable phosphorylcholine‐capped polyurethane

To obtain controllable and biocompatible drug carriers, a series of amphiphilic biodegradable multiblock polyurethanes end‐capped by phosphorylcholine were designed and synthesized using L ‐lysine ethyl ester diisocyanate (LDI), poly(lactic acid)‐poly(ethylene glycol)‐poly(lactic acid) (PLA‐PEG‐PLA), 1,4‐butanediol (BDO), and 4‐hydroxy butyl phosphorylcholine (BPC) was used as end‐capper to improve their biocompatibility and provide them with tailored micellization characteristics. The resulting polyurethanes were fully characterized with proton nuclear magnetic resonance spectroscopy (¹H NMR), Fourier transform infrared spectroscopy (FT‐IR), gel permeation chromatograph (GPC), and differential scanning calorimetry (DSC). More importantly, these phosphorylcholine‐capped polyurethanes can self assemble into micelles that are smaller than 100 nm in diameter. Their particle sizes, size distributions, and zeta potentials can also be tailored by varying the phosphorylcholine content. The incorporation of phosphorylcholine into these polyurethanes has significantly affected their degree of microphase separation, bulk and micelle degradation rates. This work provides a new and facile approach to prepare amphiphilic block copolymer micelles with controllable performances, which could be useful for drug delivery and bioimaging applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

pH‐responsive polymer core–shell nanospheres for drug delivery

Stimuli‐responsive polymer nanoparticles are playing an increasingly more important role in drug delivery applications. However, limited knowledge has been accumulated about processes which use stimuli‐responsive polymer nanospheres (matrix nanoparticles whose entire mass is solid) to carry and deliver hydrophobic therapeutics in aqueous solution. In this research, pyrene was selected as a model hydrophobic drug and a pyrene‐loaded core‐shell structured nanosphere named poly(DEAEMA)‐poly(PEGMA) was designed as a drug carrier where DEAEMA and PEGMA represent 2‐(diethylamino)ethyl methacrylate and poly(ethylene glycol) methacrylate, respectively. The pyrene‐loaded core‐shell nanospheres were prepared via an in situ two‐step semibatch emulsion polymerization method. The particle size of the core‐shell nanosphere can be well controlled through adjusting the level of surfactant used in the polymerization where an average particle diameter of below 100 nm was readily achieved. The surfactant was removed via a dialysis operation after polymerization. Egg lecithin vesicles (liposome) were prepared to mimic the membrane of a cell and to receive the released pyrene from the nanosphere carriers. The in vitro release profiles of pyrene toward different pH liposome vesicles were recorded as a function of time at 37 °C. It was found that release of pyrene from the core‐shell polymer matrix can be triggered by a change in the environmental pH. In particular the pyrene‐loaded nanospheres are capable of responding to a narrow window of pH change from pH = 5, 6, to 7 and can achieve a significant pyrene release of above 80% within 90 h. The rate of release increased with a decrease in pH. A first‐order kinetic model was proposed to describe the rate of release with respect to the concentration of pyrene in the polymer matrix. The first‐order rate constant of release k was thus determined as 0.049 h^?1 for pH = 5; 0.043 h^?1 for pH = 6; and 0.035 h^?1 for pH = 7 at 37 °C. The release of pyrene was considered to follow a diffusion‐controlled mechanism. The synthesis and encapsulation process developed herein provides a new approach to prepare smart nanoparticles for efficient delivery of hydrophobic drugs. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4440–4450     

Synthesis and characterization of well‐defined diblock and triblock copolymers of poly(N‐isopropylacrylamide) and poly(ethylene oxide)

Well‐defined diblock and triblock copolymers composed of poly(N‐isopropylacrylamide) (PNIPAM) and poly(ethylene oxide) (PEO) were successfully synthesized through the reversible addition–fragmentation chain transfer polymerization of N‐isopropylacrylamide (NIPAM) with PEO capped with one or two dithiobenzoyl groups as a macrotransfer agent. ¹H NMR, Fourier transform infrared, and gel permeation chromatography instruments were used to characterize the block copolymers obtained. The results showed that the diblock and triblock copolymers had well‐defined structures and narrow molecular weight distributions (weight‐average molecular weight/number‐average molecular weight < 1.2), and the molecular weight of the PNIPAM block in the diblock and triblock copolymers could be controlled by the initial molar ratio of NIPAM to dithiobenzoate‐terminated PEO and the NIPAM conversion. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4873–4881, 2004     

Synthesis and properties of monocleavable amphiphilic comblike copolymers with alternating PEG and PCL grafts

Symmetric reduction‐responsive amphiphilic comblike copolymers mid‐disulfide‐functionalized comblike copolymers with alternating copolymer comprised of styrenic unit and N‐(2‐hydroxyethyl) maleimide (HEMI) unit (poly(St‐alt‐HEMI)) backbones and alternating PEG and PCL side chains (S‐CP(PEG‐alt‐PCL)) with poly(St‐alt‐HEMI) backbones and alternating poly(ε‐caprolactone) (PCL) and poly(ethylene glycol) (PEG) side chains were synthesized and used as nanocarriers for in vitro release of doxorubicin. The target copolymers with predetermined molecular weight and narrow molecular weight distribution (M_w/M_n = 1.15–1.20) were synthesized by reversible addition‐fragmentation chain transfer (RAFT) copolymerization of vinylbenzyl‐terminated PEG and N‐(2‐hydroxyethyl) maleimide mediated by a disulfide‐functionalized RAFT agent S‐CPDB, and followed by ring‐opening polymerization of ε‐caprolactone. When compared with linear block copolymer comprised of poly(ethylene glycol) (PEG) and poly(?‐caprolactone) (PCL) segments (PEG‐b‐PCL) copolymers, comblike copolymers with similar PCL contents usually exhibited decreased crystallization temperature, melting temperature, and degree of crystallinity, indicating the significant influence of copolymer architecture on physicochemical properties. Dynamic light scattering measurements revealed that comblike copolymers were liable to self‐assemble into aggregates involving vesicles and micelles with average diameter in the range of 56–226 nm and particle size distribution ranging between 0.07 and 0.20. In contrast to linear copolymer aggregates, comblike copolymer aggregates with similar compositions were of improved storage stability and enhanced drug‐loading efficiency. In vitro drug release confirmed the disulfide‐linked comblike copolymer aggregates could rapidly release the encapsulated drug when triggered by 10 mM DL ‐dithiothreitol. These reduction‐sensitive, biocompatible, and biodegradable aggregates have a potential as controlled delivery vehicles. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Molecular dynamics simulations of PNIPAM‐co‐PEGMA copolymer hydrophilic to hydrophobic transition in NaCl solution

Classical molecular dynamics simulations were carried out to investigate the hydrophilic to hydrophobic transition of PNIPAM‐co‐PEGMA close to its lower critical solution temperature (LCST) in 1 M NaCl solution. PNIPAM‐co‐PEGMA is a copolymer of poly(N‐isopropylacrylamide) (PNIPAM) and poly(ethylene glycol) methacrylate (PEGMA). The copolymer consists of 38 monomer units of NIPAM with two PEGMA chains attached to the PNIAPM backbone. The PNIPAM‐co‐PEGMA was observed to go through the hydrophilic?hydrophobic conformational change for simulations at temperature slightly above its LCST. Na⁺ ions were found to bind strongly and directly with amide O, even more strongly with the O atoms on PEGAMS chains, whereas Cl^? ions only exhibit weak interaction with the polymer. Significantly a novel caged stable metal‐organic complex involving a Na⁺ ion coordinated by six O atoms from the copolymer was observed after the PNIPAM‐co‐PEGMA copolymer went through conformational transition to form a hydrophobic folded structure. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Synthesis and characterization of saccharide‐based latex particles

The synthesis of new polymer colloids based on renewable resources, such as sugar‐derived monomers, is nowadays a matter of interest. These new polymeric particles should be useful in biomedical applications, such as drug delivery, because of their assumed biodegradability. In this work, two new families of polymer latex particles, based on a sugar‐derived monomer, 3‐O‐methacryloyl‐1,2:5,6‐di‐O‐isopropylidene‐α‐D ‐glucofuranose (3‐MDG), were produced and characterized. The syntheses of poly(3‐MDG) crosslinked particles and those obtained by copolymerization with methacrylic acid (MAA), poly(3‐MDG‐co‐MAA) crosslinked particles, were prepared by surfactant‐free emulsion polymerization in a batch reactor. The average particle diameter evolutions, the effect of pH of the dispersion medium on the final average diameters, together with the microscopic and morphological analysis of the particle's surface and inner dominium, were analyzed. Poly(3‐MDG‐co‐EGDMA) stable particles were obtained by adding low amounts of initiator. The surface‐charge density of these particles corresponded to the sulfate groups coming from the initiator. In the second family of latices, poly(3‐MDG‐co‐MAA‐co‐EGDMA) particles, DCP measurements and SEM and TEM observations showed that the sizes and surface characteristics depended on the amounts of MAA and crosslinker used in the reaction mixture. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 443–457, 2006     

pH‐sensitive polymeric micelles based on amphiphilic polypeptide as smart drug carriers

A series of amphiphilic diblock copolymers having poly(ethylene glycol) (PEG) as one block and a polypeptide as the other block were synthesized by ring‐opening polymerization using PEG‐amine as a macroinitiator. These polymers were characterized by ¹H‐NMR and gel permeation chromatography. The influence of the substitution ratio of tertiary amine‐containing groups on the pH sensitivity of the polymers was investigated in detail. Core/shell‐structured micelles were fabricated from these polymers using an organic solvent‐free method. pH‐ and concentration‐dependent micellization behaviors were investigated by dynamic light scattering and fluorescence microscopy. Micelles loaded with doxorubicin, selected as a model drug, showed restricted drug release at physiological pH but accelerated drug release at tumor extracellular pH. Collectively, our findings suggest that these pH‐sensitive micelles might have great potential for cancer therapy applications. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4175–4182