Amphiphilic chitosan graft copolymer via combination of ROP, ATRP and click chemistry: Synthesis, self-assembly, thermosensitivity, fluorescence, and controlled drug release

Novel amphiphilic chitosan-g-poly(ε-caprolactone)-(g-poly(2-(2-methoxyethoxy)ethyl methacrylate)-co-oligo(ethylene glycol) methacrylate) (CS-g-PCL(-g-P(MEO₂MA-co-OEGMA))) copolymers with double side chains of PCL and P(MEO₂MA-co-OEGMA) were synthesized via combination of ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP) and click chemistry. The molar ratio of PCL and P(MEO₂MA-co-OEGMA) was varied through variation of the feed ratio and the coupling efficiency of click chemistry is comparatively high. The graft copolymers can assemble into spherical micelles. The micelles show thermosensitive properties and the lower critical solution temperatures (LCSTs) were influenced by CS chains and the ratio of PCL and P(MEO₂MA-co-OEGMA) side chains. Moreover, the micelles can reversibly swell and shrink in response to the change of temperatures. Furthermore, the micelles present obvious fluorescence and the fluorescent intensity can be adjusted by altering the temperatures. The investigation of doxorubicin release from the micelles indicated that the release rate of the drug could be effectively controlled by altering the temperatures.     

Synthesis of novel temperature responsive PEG-b-[PCL-g-P(MEO2MA-co-OEGMA)]-b-PEG (tBG) triblock-graft copolymers and preparation of tBG/graphene oxide composite hydrogels via click chemistry

Novel triblock-graft copolymers, poly ethylene glycol-b-[poly(ε-caprolactone)-g-poly(2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methacrylate)]-b-poly ethylene glycol (PEG-b-[PCL-g-P(MEO₂MA-co-OEGMA)]-b-PEG) (tBG), were synthesized via ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). In the synthesis process, temperature responsive P(MEO₂MA-co-OEGMA) chains were grafted onto the PCL block of triblock copolymer PEG-b-PCL-b-PEG to improve its hydrophilicity. This method succeeded in increasing the solubility of PEG-b-PCL-b-PEG in water, and more importantly, endowing PEG-b-PCL-b-PEG with temperature sensitivity. By adjusting the feed ratio of 2-(2-methoxy ethoxy) ethyl methacrylate (MEO₂MA) and oligo (ethylene glycol) methacrylate (OEGMA) monomers, the lower critical solution temperature (LCST) of the tBG can be realized at about 37 °C. Taking advantage of the excellent mechanical property of graphene sheets, alkyne-functionalized graphene oxide (alkyne-GO) was introduced to cross-link tBGs and prepare tBG/GO composite hydrogel through click reaction between tBG-N₃ and alkyne-GO. Different from traditional cross-linkers, alkyne-GO acts as reinforcing filler in the composite hydrogel. Benefiting from superior properties of PCL, PEG, P(MEO₂MA-co-OEGMA) and GO, the as-prepared temperature responsive tBG/GO hydrogel exhibits excellent mechanical strength and toughness, demonstrating future potential applications in tissue engineering and biotechnology fields.     

Micellization and sol-gel transition of novel thermo- and pH-responsive ABC triblock copolymer synthesized by RAFT

A well-defined thermo- and pH-responsive ABC-type triblock copolymer monomethoxy poly(ethylene glycol)-b-poly(2-(2-methoxyethoxy) ethyl methacrylate-co-N-hydroxymethyl acrylamide)-b-poly(2-(diethylamino) ethyl methacrylate), mPEG-b-P(MEO₂MA-co-HMAM)-b-PDEAEMA, was synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT). The ABC-type triblock copolymer was endowed thermo- and pH-responsive, corresponding to the thermosensitive properties of P(MEO₂MA-co-HMAM) and pH-responsive properties PDEAEMA segments, respectively. The thermo- and pH-responsive properties of copolymer aqueous solutions were studied by UV transmittance measurements, dynamic light scattering (DLS), transmission electron microscopy (TEM). The results showed that the N-hydroxymethyl acrylamide (HMAM) content in triblock copolymer affected the lower critical solution temperature (LCST) of the triblock copolymer aqueous solution. The copolymer self-assembled into core-shell micelles, with the thermoresponsive P(MEO₂MA-co-HMAM) block and the hydrophilic PEG block as the shell, the hydrophobic PDEAEMA block as the core, in alkaline solution at room temperature. While in acidic media, when the temperature above the lower critical solution temperature (LCST) of the triblock copolymer aqueous solution, the copolymer self-assembled into P(MEO₂MA-co-HMAM)-core micelles with mixed hydrophilic PEG and pH-responsive PDEAEMA coronas. Sol-gel transition temperature (T_sol-gel) for the triblock copolymer determined by vial inversion test further indicated that it is dependent on the concentration of the triblock copolymers and solution pH. Copolymer hydrogel loaded with bovine serum albumin (BSA) were used for the sustained release study. The results indicated that the hydrogel was a promising candidate for controlling protein drug delivery.     

Novel amphiphilic temperature responsive graft copolymers PCL-<Emphasis Type="Italic">g</Emphasis>-P(MEO<Subscript>2</Subscript>MA-<Emphasis Type="Italic">co</Emphasis>-OEGMA) via a combination of ROP and ATRP: synthesis,characterization, and sol-gel transition

A series of well-defined novel amphiphilic temperature-responsive graft copolymers containing PCL analogues P(αClεCL-co-εCL) as the hydrophobic backbone, and the hydrophilic side-chain PEG analogues P(MEO₂MA-co-OEGMA), designated as P(αClεCL-co-εCL)-g-P(MEO₂MA-co-OEGMA) have been prepared via a combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The composition and structure of these copolymers were characterized by ¹H NMR and GPC analyses. The self-assembly behaviors of these amphiphilic graft copolymers were investigated by UV transmittance, a fluorescence probe method, dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. The results showed that the graft copolymers exhibited the good solubility in water, and was given the low critical temperature (LCST) at 35(±1) °C, which closed to human physiological temperature. The critical micelle concentrations (CMC) of P(αClεCL-co-εCL)-g-P(MEO₂MA-co-OEGMA) in aqueous solution were investigated to be 2.0 × 10^?3, 9.1 × 10^?4 and 1.5 × 10^?3 mg·mL^?1, respectively. The copolymer could self-assemble into sphere-like aggregates in aqueous solution with diverse sizes when changing the environmental temperature. The vial inversion test demonstrated that the graft copolymers could trigger the sol-gel transition which also depended on the temperature.     

Temperature and pH responsive hydrogels based on polyethylene glycol analogues and poly(methacrylic acid) via click chemistry

A novel temperature responsive copolymer, poly[2‐(2‐methoxyethoxy)ethyl methacrylate‐co‐oligo(ethylene glycol)methacrylate‐co‐N‐hydroxymethyl acrylamide] [P(MEO₂MA‐co‐OEGMA‐co‐HMAM)], was synthesized by atom transfer radical polymerization. pH responsive poly(methacrylic acid) (PMAA) was synthesized by reversible addition‐fragmentation chain transfer polymerization. After the hydroxyl groups on P(MEO₂MA‐co‐OEGMA‐co‐HMAM) were transformed into azide groups and the carboxyl groups on PMAA were transformed into alkyne groups respectively, a novel temperature and pH responsive hydrogel was fabricated by click chemistry between the azide‐P(MEO₂MA‐co‐OEGMA‐co‐HMAM) and alkyne‐PMAA in the presence of CuSO₄ and sodium ascorbate in aqueous solution. The rheological kinetics of gel formation demonstrated that gelation had commenced within 5 min at 25 °C, since then the storage modulus (G′) was higher than the loss modulus (G″). SEM images of hydrogel morphology and the swelling ratios of hydrogel at different temperatures and pH proved that the formed hydrogel had temperature and pH sensitivities. Bovine serum albumin was used as a model to evaluate the sustained release of the hydrogel; the results indicated that the hydrogel was a promising candidate for controlling protein drug delivery. © 2015 Society of Chemical Industry     

Synthesis of well‐defined comb‐like amphiphilic copolymers with protonizable units in the pendent chains: 2. Poly(2‐(dimethylamino)ethyl methacrylate) grafted poly(methyl methacrylate‐co‐2‐hydroxyethyl methacrylate) copolymers and their association behavior in aqueous solution

Narrow‐distribution, well‐defined comb‐like amphiphilic copolymers are reported in this work. The copolymers are composed of poly(methyl methacrylate‐co‐2‐hydroxyethyl methacrylate) (P(MMA‐co‐HEMA)) as the backbones and poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) as the grafted chains, with the copolymer backbones being synthesized via atom‐transfer radical polymerization (ATRP) and the grafted chains by oxyanionic polymerization. The copolymers were characterized by gel permeation chromatography (GPC), Fourier‐transform infrared (FT‐IR) spectroscopy and ¹H NMR spectroscopy. The aggregation behavior in aqueous solutions of the comb‐like amphiphilic copolymers was also investigated. ¹H NMR spectroscopic and surface tension measurements all indicated that the copolymers could form micelles in aqueous solutions and they possessed high surface activity. The results of dynamic light scattering (DLS) and scanning electron microscopy (SEM) investigations showed that the hydrodynamic diameters of the comb‐like amphiphilic copolymer aggregates increased with dilution. Because of the protonizable properties of the graft chains, the surface activity properties and micellar state can be easily modulated by variations in pH. Copyright © 2004 Society of Chemical Industry     

Synthesis and characterization of AB2-type star polymers via combination of ATRP and click chemistry

Homo/miktoarm star polymers were successfully synthesized via combination of the “arm-first” and “coupling-onto” strategies. Firstly, the multifunctional coupling agent (core), 2, 4, 6-tris(3-ethynylphenyl)-1,3,5-triazine-2,4,6-triamine (TPTTA), was synthesized. Secondly, the linear polystyrene-Cl (PS-Cl) and poly(2-(dimethylamino)ethyl methacrylate)-Br (PDMAEMA-Br) were prepared by atom transfer radical polymerization (ATRP) method. Then, the linear PS-Cl and PDMAEMA-Br chains were modified by a nucleophilic substitution reaction with sodium azide. Finally, homo/miktoarm star polymers PS₃ and PS(PDMAEMA)₂ were designed by click reaction between the core (TPTTA) and the arm precursor (PS-N₃ or PDMAEMA-N₃). The structures of the PS₃, PS(PDMAEMA)₂ and the precursors were all characterized by NMR, FT-IR, UV and GPC analysis. Moreover, the self-assembly behaviors of the miktoarm amphiphilic copolymer PS(PDMAEMA)₂ was also investigated by transmission electron microscopy (TEM).     

Temperature,pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for controlled release

Temperature, pH, and reduction triple‐stimuli‐responsive inner‐layer crosslinked micelles as nanocarriers for drug delivery and release are designed. The well‐defined tetrablock copolymer poly(polyethylene glycol methacrylate)–poly[2‐(dimethylamino) ethyl methacrylate]–poly(N‐isopropylacrylamide)–poly(methylacrylic acid) (PPEGMA‐PDMAEMA‐PNIPAM‐PMAA) is synthesized via atom transfer radical polymerization, click chemistry, and esterolysis reaction. The tetrablock copolymer self‐assembles into noncrosslinked micelles in acidic aqueous solution. The core‐crosslinked micelles, shell‐crosslinked micelles, and shell–core dilayer‐crosslinked micelles are prepared via quaternization reaction or carbodiimide chemistry reaction. The crosslinked micelles are used as drug carriers to load doxorubicin (DOX), and the drug encapsulation efficiency with 20% feed ratio reached 59.2%, 73.1%, and 86.1%, respectively. The cumulative release rate of DOX is accelerated by single or combined stimulations. The MTT (3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay verifies that the inner‐layer crosslinked micelles show excellent cytocompatibility, and DOX‐loaded micelles exhibit significantly higher inhibition for HepG2 cell proliferation. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46714.     

Two‐component “Onionlike” micelles with a PPO core,a PDMAEMA shell and a PEO corona: formation and crosslinking

BACKGROUND: Chemical or physical crosslinking of supramolecular assemblies gives them stability in a wide range of environments. Much attention is paid to multilayer (onion‐like) polymeric micelles because their functionality is higher than classic core‐shell micelles. This work reports on the formation and crosslinking of onion‐like micelles prepared by mixing two different block copolymers containing a crosslinkable poly(dimethylaminoethyl methacrylate) (PDMAEMA) block. RESULTS: Block copolymers of a crosslinkable PDMAEMA block were synthesized by atom transfer radical polymerization of 2‐(dimethylamino)ethyl methacrylate (DMAEMA) from poly(propylene oxide) (PPO) or poly(ethylene oxide) (PEO) macroinitiators. The (PDMAEMA₁₃)‐block‐PPO₆₉‐block‐(PDMAEMA₁₃) triblock formed wormlike core‐shell micelles, which were converted into ellipsoidal onion‐like micelles on mixing with the PEO₄₅‐block‐P(DMAEMA₈‐co‐MMA₄) diblock. Onion‐like micelles were crosslinked by quaternization of DMAEMA units. CONCLUSION: Formation of onion‐like micelles by mixing two different AB (ABA) and B′C block copolymers and their subsequent crosslinking is a valuable approach towards stabilized supramolecular assemblies of a higher complexity and functionality than the individual constitutive components. Copyright © 2008 Society of Chemical Industry     

A novel thermosensitive triblock copolymer from 100% renewably sourced poly(trimethylene ether) glycol

Bio‐based amphiphilic triblock copolymers with 100% renewably sourced poly(trimethylene ether) glycol (PO3G) as the hydrophobic blocks and statistical copolymer of 2‐(2‐methoxyethoxy)ethyl methacrylate (MEO₂MA) and oligo(ethylene glycol)methacrylate (OEGMA) [P(MEO₂MA‐stat‐OEGMA)] as the hydrophilic blocks are synthesized and characterized. It is found that the molar ratio of MEO₂MA/OEGMA among the resulting copolymers is approximately 70/30. The degree of polymerization (DP) of P(MEO₂MA‐stat‐OEGMA) block ranges from 16 to 90, and the DP of PO3G block is fixed at 35. The amphiphilic copolymers could form core‐shell micelles self‐assembly in aqueous solution at low concentrations, and the micelles are in spherical shape with sizes varying from 121 to 188 nm. With the increasing length of hydrophilic blocks, the critical micelle concentration increases from 2.15 to 13.8 mg L^?1, and the lower critical solution temperature improves from 32.5 to 38.4 °C. The in vitro doxorubicin (DOX) release study shows that all DOX‐loaded micelles have a higher release rate at 37 °C than that at 25 °C. Cytotoxicity test reveals that the blank micelles are nearly nontoxic. These results indicate that the block copolymer micelles containing 100% renewably sourced PO3G can serve as a potential drug delivery carrier. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46112.     

Temperature induced micellization and aggregation of biocompatible poly (oligo(ethylene glycol)methyl ether methacrylate) block copolymer analogs in aqueous solutions

A series of well-defined block copolymers composed of di(ethylene glycol) methyl ether methacrylate (188 g/mol) and oligo(ethylene glycol) methyl ether methacrylate (300 g/mol), PMEO₂MA-b-(PMEO₂MA-stat-POEGMA₃₀₀), were successfully synthesized at room temperature via a two-step atom transfer radical polymerization (ATRP) process using 1,1,4,7,10,10-hexamethyl triethylene tetramine (HMTETA) as the ligand. The ratio of MEO₂MA/OEGMA₃₀₀ in the second block controls the thermal behaviors of these copolymers. When the ratio of MEO₂MA/OEGMA₃₀₀ is 80/20, only one thermal transition was observed. However, two thermal transitions were observed for MEO₂MA/OEGMA₃₀₀ ratios of 70/30 and 0/100. We believed that the first transition was associated with the formation of micelles and the second transition corresponded to the formation of larger aggregates consisting of several preformed micelles. This hypothesis was confirmed by light scattering, where the hydrodynamic radius (R_h) of the aggregates of 70/30 and 0/100 systems increased from 48 to 95 nm and 88 to 147 nm with a corresponding increase in the R_g/R_h from 0.76 to 1.1 and 0.68 to 1.0 respectively. TEM analyses confirmed the formation of spherical particles, where the sizes of these particles increased with increasing temperatures.     

Heterografted PEO-PnBA brush copolymers

A series of P[(HEMA-TMS)-co-PEOMA] graft copolymers with different amounts of incorporated macromonomer grafts were prepared by copolymerization of a PEO macromonomer (PEOMA, MW_av=1100 g/mol, DP_PEO=23) with 2-(trimethylsilyloxy)ethyl methacrylate (HEMA-TMS) using various initial ratios of the comonomers via atom transfer radical polymerization. After transformation of the HEMA-TMS units to 2-(2-bromopropionyloxy)ethyl methacrylate (BPEM), the resulting P(BPEM-co-PEOMA) copolymers were used as macroinitiators for the controlled polymerization of nBA in a ‘grafting from’ reaction. The resulting densely heterografted brush copolymers with a uniform length of PEO grafts (DP_PEO=23) and a range of lengths for the PnBA side chains (DP_PnBA=15-60) depending solely on the reaction time. Analysis of the bulk properties showed that the specific architecture of the copolymers suppresses crystallization of the PEO, and consequently leads to amorphous, homogeneous materials.     

Effect of molecular weight and polymer concentration on the triple temperature/pH/ionic strength-sensitive behavior of poly(2-(dimethylamino)ethyl methacrylate)

Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) samples were synthesized via aqueous atom transfer radical polymerization with DP_n of 35, 151, 390, and 546 and dispersity of 1.13, 1.17, 1.20, and 1.18, respectively. All samples were exposed to temperature and pH variations at different concentration of polymer and salt (NaCl). Results indicated that cloud point (T_cl) can be controlled by changing DP_n, polymer concentration, and ionic strength of solution. According to results, T_cl of the PDMAEMA chains shifted to lower temperatures with increasing solution pH at all molecular weight ranges due to deprotonation of tertiary amine groups in polymer structure. However, higher molecular weight polymers were more sensitive to pH variation especially in alkaline media. Also, higher polymer concentration acted as driving force to decrease cloud point of samples and formation of aggregates that was more predominant for higher molecular weights at alkaline media. T_cl of PDMAEMA chains decreased with increasing ionic strength even at low pH values for low molecular weight polymers.     

Reversible pH-Responsive Hydrogels of Softwood Kraft Lignin and Poly[(2-dimethylamino)ethyl Methacrylate]-based Polymers

Softwood kraft lignin (SKL) pH-responsive hydrogels were prepared through controlled aggregation using poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) and poly(2-(dimethylamino)ethyl methacrylate)-block-poly(ethylene oxide)-block-poly(2-(dimethylamino) ethyl methacrylate) triblock copolymer (PDMAEMA-co-PEO-co-PDMAEMA). At low SKL concentrations, the SKL/polymer (PDMAEMA and PDMAEMA-co-PEO-co-PDMAEMA) aqueous solutions exhibited pH-dependent aggregation arising from the formation of strong intermolecular hydrogen bonds. Decreasing the SKL/polymer weight ratio resulted in the pH-reversible soluble-insoluble (S-I) transition to become a soluble-insoluble-soluble (S-I-S) transition, which upon increasing the SKL concentration resulted in hydrogel formation. Under neutral conditions relatively strong hydrogels were formed, which upon either increasing or decreasing solution pH resulted in the hydrogels collapsing to liquid solutions, but were readily reformed upon neutralization. The effects of polymer structure, concentration, and intermolecular interactions on solution behavior and gelation are thoroughly discussed.     

A novel amphiphilic AB2 star copolymer synthesized by the combination of ring-opening metathesis polymerization and atom transfer radical polymerization

A new amphiphilic AB₂ star copolymer was synthesized by the combination of ring-opening metathesis polymerization (ROMP) and atom transfer radical polymerization (ATRP). Two different routes (methods A and B) were employed firstly to prepare the poly(oxanorbornene)-based monotelechelic polymers as the hydrophobic arm bearing dibromo-ended group via ROMP in the presence of two different terminating agents catalyzed by first generation Grubbs catalyst. The values of capping efficiency (CE) of the polymers were determined by NMR, which were 94% and 67% for methods A and B, respectively. Then, the dibromo-ended ROMP polymers were used as the macroinitiators for ATRP of 2-(dimethylamino)ethyl methacrylate (DMAEMA) to produce two hydrophilic arms. The prepared amphiphilic AB₂ star copolymers poly(7-oxanorborn-5-ene-exo,exo-2,3-dicarboxylic acid dimethyl ester)-block-bis[poly(2-(dimethylamino)ethyl methacrylate)] (PONBDM_n-b-(PDMAEMA_m)₂) with a fixed chain length of hydrophobic PONBDM and various hydrophilic PDMAEMA chain lengths can self-assemble spontaneously in water to form polymeric micelles, which were characterized by dynamic light scattering, atom force microscopy, and transmission electron microscopy measurements.     

Synthesis of pH‐ and temperature‐responsive chitosan‐graft‐poly[2‐(N,N‐dimethylamino) ethyl methacrylate] copolymer and gold nanoparticle stabilization by its micelles

Novel pH‐ and temperature‐responsive chitosan‐graft‐poly[2‐(N,N‐dimethylamino)ethyl methacrylate] (chitosan‐g‐PDMAEMA) copolymers were successfully synthesized by homogeneous atom transfer radical polymerization (ATRP) under mild conditions. Chitosan macroinitiator was prepared by phthaloylation of amino groups of chitosan and subsequent acylation of hydroxyl groups of chitosan with 2‐bromoisobutyryl bromide. The copolymers were obtained by ATRP of 2‐(N,N‐dimethylamino)ethyl methacrylate and they can self‐assemble into stable micelles in water. Hybrid micelles with a PDMAEMA corona incorporating gold nanoparticles (Au NPs) were prepared in situ via the reduction of HAuCl₄ with NaBH₄. The pH and temperature responses of the copolymer micelles and hybrid micelles were characterized using UV‐visible spectroscopy and dynamic laser light scattering. The morphology of the micelles was observed using transmission electron microscopy and atomic force microscopy. The PDMAEMA corona of the micelles acts as the ‘nanoreactor’ and the ‘anchor’ for the in situ formation and stabilization of Au NPs. Therefore, the spatial distribution of Au NPs within the micelles can be tuned by varying the temperature and pH value. Copyright © 2010 Society of Chemical Industry     

POEGMA hydrogel cross-linked by starch-based microspheres: synthesis and characterization

Hydrogels with high mechanical strength and controllable stimuli responses are highly desirable in the biomedical field. Herein, starch-based microspheres were used as macrosized cross-linkers to synthesize a series of extremely tough and thermosensitive poly[2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methyl ether methacrylate] (POEGMA) hydrogels. Scanning electron microscopy and confocal laser scanning microscopy showed that the starch-based microspheres were uniformly distributed in the hydrogel network. Compression test results indicated that the POEGMA hydrogel exhibits strength of 3.0 MPa, which is ten times greater than that of conventional hydrogels cross-linked using small molecules. This improvement in mechanical strength is attributable to the even distribution of the cross-linking points in the hydrogel, because of which the length of the flexible polymer chains between the microspheres was similar. As a result, the polymer network can readily dissipate stress. Moreover, the mechanical strength of the POEGMA hydrogel can be regulated efficiently by varying the amount of microspheres used. In addition, the POEGMA hydrogel exhibited a lower critical solution temperature (LCST) of 37°C when the 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA)/oligo(ethylene glycol) methyl ether methacrylate (OEGMA₃₀₀) mass ratio was 70/30. Further, the LCST of the POEGMA hydrogel can also be adjusted by adding salt or ethanol. The LCST decreased in the presence of sodium chloride but increased in the presence of ethanol.     

Preparation of poly(butylene succinate)‐poly[2‐(dimethylamino)ethyl methacrylate] copolymers and their applications as carriers for drug delivery

Copolymers of poly[2‐(dimethylamino)ethyl methacrylate]–poly(butylene succinate)–poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA–PBS–PDMAEMA, PDBD) were synthesized through a chain‐extension reaction. The thermal properties characterized using differential scanning calorimetry showed that the introduction of PDMAEMA chains slightly decreased the melting temperature of PBS. The water contact angle of PDBD copolymer films with media of various pH decreased with a decrease of pH. This should be ascribed to the conformational transition of PDMAEMA blocks from a compact coil to an expanding shape in accordance with the variation of the pH of the surroundings. The results of dynamic light scattering and scanning electron microscopy revealed that PDBD copolymers could form spherical micelles with small particle size and narrow particle size distribution. Furthermore, drug loading (loading content, ca 10%; encapsulation efficiency, ca 60%) and release experiments were conducted using doxorubicin as a hydrophobic model drug. The results of release experiments of copolymer nanomicelles showed that these micelles had pH‐responsive properties. © 2018 Society of Chemical Industry     

Photophysical properties and self-assembly of triblock copolymer with complexes of positively charged PDMAEMA and oppositely charged chromophores

The self-assembly and photophysical properties of a triblock copolymer with complex mid-block in THF and aqueous solution were investigated in this research. Poly(poly(ethylene glycol) methyl ether methacrylate)-block-poly(2-(dimethylamino ethyl methacrylate)-block- poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA–b–PDMAEMA–b–PPEGMA) triblock copolymer was synthesized by subsequent atom transfer radical polymerizations (ATRP) of DMAEMA and PEGMA. The PDMAEMA blocks were quaternized by a reaction with iodomethane. The complex of the positively charged PDMAEMA chain unit and sodium salt of 1-pyrenebutyric acid was prepared by mixing equimolar amount of the two components in THF/water mixture. Transmission electron microscopy and fluorescence technique results show that the triblock copolymer chains self-assemble into micelles in THF at high concentration. The critical aggregation concentration (CAC) of the triblock copolymer in THF determined by fluorescence technique is 6.8 × 10^?5 M. The triblock copolymer was also able to self-assemble into micelles in water. The value of CAC of the triblock copolymer in water is 2.0 × 10^?5 M. The photophysical properties and self-assembly structures of the triblock copolymer in aqueous solutions were influenced by added sodium chloride. After salt addition, a transition of the assembled structures from micelles to hollow structures was observed.     

Thermosensitive PMMA core/oligo(ethylene glycol)-based shell microgels as drug carriers in detoxification treatment

The core-shell structured polymer microgels were synthesized by coating the hydrophobic poly(methyl methacrylate) (PMMA) sphere cores with hydrophilic nonlinear poly(ethylene glycol)-based gel shell layer. The uniqueness of these core-shell microgels lies in the integration of the PMMA core microsphere with strong hydrophobicity and the novel oligo(ethylene glycol)-based gel layer with well-defined thermosensitivity for improving loading/release efficacy of two detoxification drugs (chlorpromazine and diltiazem). The hydrophilic shell is composed of hydrophilic copolymer of 2-(2-methoxyethoxy)ethyl methacrylate (MEO₂MA) with oligo(ethylene glycol) methyl ether methacrylates (MEO₅MA). It was found that the molar ratio of two shell monomers n(MEO₂MA)/n(MEO₅MA) of 1:6 was an ideal matching value for production of the P(MEO₂MA)/P(MEO₂MA-co-MEO₅MA) core-shell microgels with tunable volume phase transition temperature and excellent colloidal stability across the physiologically important temperature range. Moreover, chlorpromazine- and diltiazem-loaded microgels can show an obvious thermosensitive release and in vitro sustained-release characteristic up to 80 h.