Synthesis of amphiphilic temperature‐sensitive poly(N‐isopropylacrylamide)‐block‐poly(tetramethylene carbonate) block copolymers and micellar characterization

Amphiphilic thermally sensitive poly(N‐isopropylacrylamide)‐block‐poly(tetramethylene carbonate) block copolymers were synthesized by ring‐opening polymerization of tetramethylene carbonate with hydroxyl‐terminated poly(N‐isopropylacrylamide) (PNiPAAm) as macro‐initiator in the presence of stannous octoate as catalyst. The synthesis involved PNiPAAm bearing a single terminal hydroxyl group prepared by telomerization using 2‐hydroxyethanethiol as a chain‐transfer agent. The copolymers were characterized using ¹H NMR and Fourier transform infrared spectroscopy and gel permeation chromatography. Their solutions show reversible changes in optical properties: transparent below the lower critical solution temperature (LCST) and opaque above the LCST. The LCST depends on the polymer composition and the media. Owing to their amphiphilic characteristics, the block copolymers form micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range 1.11–22.9 mg L^?1. Increasing the hydrophobic segment length or decreasing the hydrophilic segment length in the amphiphilic diblock copolymers produces lower CMCs. A core‐shell structure of the micelles is evident from ¹H NMR analyses of the micelles in D₂O. Transmission electron microscopic analyses of micelle morphology show a spherical structure of both blank and drug‐loaded micelles. The blank and drug‐loaded micelles have an average size of less than 130 nm. Observations show high drug‐entrapment efficiency and drug‐loading content for the drug‐loaded micelles. Copyright © 2010 Society of Chemical Industry     

New water soluble azobenzene-containing diblock copolymers: synthesis and aggregation behavior

Homopolymers of azobenzene (azo) methacrylates with different substituents and their diblock copolymers with poly(2-(dimethylamino)ethyl methacrylate p(DMAEMA) were synthesized via atom transfer radical polymerization (ATRP). Controlled/‘living’ ATRP of azo methacrylates were achieved up to ∼50% conversion, after which deviation occurred. It was found that the copolymerization rate of 6-[4-phenylazo]phenoxy]hexylmethacrylate (PPHM) from p(DMAEMA) macroinitiator was almost identical to that for the homopolymerization of PPHM monomer, with k_app∼0.0078 min⁻¹. For the copolymerizations, almost complete incorporation of the azo methacrylate monomers could be obtained with low molecular weight macroinitiator (PDMAEMA)-Cl, whereas macroinitiators of long chain length did not give full conversion, most likely due to chain floding and steric hindrance caused by the bulk azo monomers. Because azo monomers are highly hydrophobic, only the diblock copolymers with short azo segment were soluble in water which self-assembled into micellar particles. The effect of photo-induced trans-cis isomerization on lower critical solution temperature (LCST) and surface tension were studied. The LCST of the diblock copolymers increased upon irradiation by UV light due to the cis conformers being more hydrophilic. However, the trans-cis isomerization had only small effect on the critical micelle concentration (cmc) and γ_cmc of azo methacrylate block copolymers, due to the formation of compact core of the micelles. The formations of core-shell micelles were established from LLS and TEM studies. All the three azo methacrylate amphiphilic block copolymers formed hard core-shell micelles with relatively small R_h values of 31 nm for p(DMAEMA₁₇₂-b-BPHM₇), 26 nm for p(DMAEMA₁₇₂-b-CPHM₇) and 32 nm for p(DMAEMA₁₇₂-b-PPHM₉). Whereas for the azo acrylate copolymer, p(DMAEMA₁₇₂-b-BPHA₆), large micelles with R_h∼78 nm with loose core was formed.     

Synthesis and characterization of amphiphilic triblock-graft PEG-(<Emphasis Type="Italic">b</Emphasis>-PαN<Subscript>3</Subscript>CL-<Emphasis Type="Italic">g</Emphasis>-Alkyne)<Subscript>2</Subscript> degradable copolymers

The study proposes a straightforward strategy for synthesizing novel, amphiphilic triblock-graft PEG-(b-PαN₃CL-g-Alkyne)₂ degradable copolymers. First, this investigation performs copolymerization of α-chloro-ε-caprolactone (αClCL) using α,ω-dihydroxyl-terminated macroinitiator poly(ethylene glycol) (PEG) and stannous octoate as the catalyst. In a second step, the current work converts pendent chlorides into azides by reacting with sodium azide. Finally, various kinds of terminal alkynes react with pendent azides by copper-catalyzed Huisgen’s 1,3-dipolar cycloaddition, thus a “click” reaction. These copolymers are characterized by differential scanning calorimetry (DSC), ¹H NMR, IR and gel permeation chromatography. The resulting triblock-graft copolymers exhibit lower crystallinity and melting temperature with respect to the original PEG. The triblock-graft copolymers form micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range of 1.58–8.62 mg L⁻¹, depending on polymer composition. The ¹H NMR spectrum of micelles in D₂O demonstrate only the PEG signal and thus confirm the PCL-g-Alkyne blocks constitute the micelle core, while the central PEG block constitutes the micelle shell. The hydrophilic segment lengths influence the micelle shape. The mean hydrodynamic diameters of micelles from DLS range from 90–200 nm. The work describes drug entrapment efficiency and drug loading content of micelles depending on the composition of triblock-graft polymers.      

Association behavior of thermo-responsive block copolymers based on poly(vinyl ethers)

Thermo-sensitive nanosized structures have been prepared in water from poly(methyl vinyl ether)-block-poly(isobutyl vinyl ether) (PMVE-b-PIBVE) block copolymers. The composition and the architecture (diblock and triblock architectures) of the PMVE-b-PIBVE copolymers have been varied. The investigated copolymers had an asymmetric composition with a major PMVE block. While the PIBVE blocks are hydrophobic, the PMVE blocks are hydrophilic at room temperature and become hydrophobic above their demixing temperature (around 36 °C) as a result of the lower critical solution temperature (LCST) behavior. At room temperature, the amphiphilic copolymers aggregate in water above a critical micelle concentration, which has been experimentally measured by hydrophobic dye solubilization. The hydrodynamic diameter of the structures formed above the cmc has been measured by dynamic light scattering (DLS) while their morphology has been studied by transmission electron microscopy (TEM). ¹H NMR measurements in D₂O at room temperature reveal that the aggregates contain PIBVE insoluble regions surrounded by solvated PMVE chains. These investigations have shown that polydisperse spherical micelles are formed for asymmetric PMVE-b-PIBVE copolymers containing at least 9 IBVE units. For copolymers containing less IBVE units, loose aggregates are formed.Finally, the thermo-responsive, reversible properties of these structures have been investigated. Above the cloud point of the copolymers, the loose aggregates precipitate while the micelles form large spherical structures.     

Synthesis and characterization of amphiphilic block copolymers from poly(ethylene glycol)methyl ether and 4-methyl-?-caprolactone or 4-phenyl-?-caprolactone

MPEG-b-PMCL and MPEG-b-PBCL diblock copolymers were synthesized by ring-opening polymerization of 4-methyl-?-caprolactone (MCL) or 4-phenyl-?-caprolactone (BCL) using monomethoxy poly(ethylene glycol) (MPEG, M_n = 550 or 2000 g mol⁻¹) as the macroinitiator and SnOct₂ as the catalyst. These copolymers were characterized by differential scanning calorimetry (DSC), ¹H NMR, ¹³C NMR, and gel permeation chromatography. The thermal properties (T_g and T_m) of the diblock copolymers depend on the composition of polymers. When larger amount of MCL or BCL was incorporated into the macromolecular backbone there was an increase in T_g. Their micellar characteristics in the aqueous phase were investigated by fluorescence spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). The block copolymers formed micelles in the aqueous phase with critical micelle concentrations (CMCs) in the range of 0.5-2.9 mg L⁻¹, depending on the composition of polymers. The lengths of hydrophilic segment influence the shape of micelle. The mean hydrodynamic diameters of micelles from DLS were in the range of 70-140 nm. The drug entrapment efficiency and the drug-loading content of micelles depending on the composition of block polymers were described.     

Micellization and phase transition behavior of thermosensitive poly(N-isopropylacrylamide)-poly(?-caprolactone)-poly(N-isopropylacrylamide) triblock copolymers

Thermosensitive triblock copolymers with two hydrophilic poly(N-isopropylacrylamide) blocks flanking a central hydrophobic poly(?-caprolactone) block were synthesized by atom transfer radical polymerization. Core-shell micellization of the triblock copolymers was inferred from the ¹H NMR spectra derived in two different solvent environments (CDCl₃ and D₂O). The micellar characteristics of these amphiphilic triblock copolymers were studied by pyrene fluorescence techniques, dynamic light scattering and transmission electron microscopy. The critical micelle concentrations of the triblock copolymers were in the range of 4-16 mg/L and the partition coefficients were in the range of 3.10 × 10⁴ to 2.46 × 10⁵. The mean diameters of the micelles, measured by light scattering, were between 90 and 120 nm. The temperature sensitivity of the triblock copolymers was demonstrated by the phase transition of a 250 mg/L aqueous polymer solution at the lower critical solution temperature (LCST). The enthalpy of the phase transition was determined by differential scanning calorimetry. PM3 quantum mechanical calculation method was used to understand the intermolecular interactions between the copolymer and the water molecules. A modular approach was used to simulate the phase transition observed at the LCST.     

Synthesis and characterization of amphiphilic functional polyesters by ring-opening polymerization and click reaction

During this work we have prepared novel amphiphilic graft-block (PαN₃CL-g-alkyne)-b-PCL functional polyesters, comprising poly(α-azido-ε-caprolactone-graft-alkyne) (PαN₃CL-g-alkyne) as the hydrophilic segment and poly(ε-caprolactone) (PCL) as the hydrophobic segment, by ring-opening polymerization of ε-caprolactone (ε-CL) with hydroxyl-terminated macroinitiator PαClCL, substituting pendent chloride with sodium azide. The copolymers were subsequently used for grafting of 2-propynyl-terminal alkyne moieties by the Cu(I)-catalyzed Huisgen’s 1,3-dipolar cycloaddition, thus producing a “click” reaction. ¹H NMR, FT-IR, GPC, and differential scanning calorimetry (DSC) examined the characteristics of the copolymers. Grafting of PMEs or PMPEGs onto the PαN₃CL-b-PCL caused these amphiphilic copolymers to self-assemble into micelles in the aqueous phase. Fluorescence, dynamic light scattering (DLS) and transmission electron microscopy (TEM) then examined these micelles. The critical micelle concentration (CMC) ranged from 8.2 mg L⁻¹ to 39.8 mg L⁻¹ at 25 °C and the average micelle size ranged from 140 to 230 nm. The hydrophilicity and length of the hydrophilic segment influenced micelle stability. The current study describes the drug entrapment efficiency and drug loading content of the micelles, dependent on the composition of graft-block polymers. The results from in vitro cell viability assays indicated that (PαN₃CL-g-alkyne)-b-PCL shows low cytotoxicity.     

Synthesis and self-assembly of comb-like amphiphilic Doxifluridine-poly(?-caprolactone)-graft-poly(γ-glutamic acid) copolymer

Advances in amphiphilic copolymers can potentially be exploited in drug or gene delivery. This study develops novel comb-like amphiphilic copolymers that comprise poly(γ-glutamic acid) (γ-PGA) as a hydrophilic backbone and Doxifluridine-poly-(?-caprolactone) (5′-deoxy-5-fluorouridine-poly(?-caprolactone), 5′DFUR-PCL) as a hydrophobic side chain. A novel 5′DFUR-PCL polymer was synthesized with antitumor agent Doxifluridine (5′DFUR) as the initiator via the ring-opening polymerization of ?-caprolactone (?-CL) using tin(II) 2-ethylhexanoate (Sn(Oct)₂) as the catalyst. The 5′DFUR-PCL polymer was then grafted on γ-PGA to yield a 5′DFUR-PCL-γ-PGA comb-like copolymer with the help of 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide (EDC). The characteristics of these copolymers were examined by ¹H NMR, FT-IR, GPC, contact angle measurement and thermal properties. Grafting 5′DFUR-PCL would significantly increase the contact angle and decrease the melting temperature (T_m) of the copolymers. The micelles self-assembled from these amphiphilic copolymers were formed in an aqueous phase and were examined via fluorescence approaches, dynamic light scattering (DLS) and transmission electron microscopy (TEM). The average sizes of the micelles were in the range from 130 to 230 nm and their zeta potentials were negative and less than −16.7 mV. The critical micelle concentration (CMC) was from 1.49 mg/L to 4.63 mg/L at 25 °C. TEM images demonstrated that the micelles were spherical and clearly had a core-shell structure.     

Structural effect of a series of block copolymers consisting of poly(N-isopropylacrylamide) and poly(N-hydroxyethylacrylamide) on thermoresponsive behavior

Well-defined diblock and triblock copolymers consisting of poly(N-isopropylacrylamide) (PNIPAM) and poly(N-hydroxyethylacrylamide) (PHEAA) were prepared using the atom transfer radical polymerization (ATRP) method. The number-average molecular weight and fraction of each segment were precisely controllable by adjusting the monomer/initiator ratio in feed. The lower critical solution temperature (LCST) of a series of block copolymers with different compositions was examined using a turbidimetry analysis. The copolymers with a relatively lower molar fraction of HEAA units in the polymer chain exhibited phase transition phenomenon, in which the LCST depended on the fraction in the copolymer. On the other hand, the LCST disappeared for the copolymers with higher HEAA unit molar fractions. The ¹H NMR measurement clarified that the disappearance of the LCST was attributed to the formation of the water-soluble micelle. Furthermore, the thermoresponsive property of the series of block copolymers was elucidated on the basis of the structural effect of the copolymer, which includes the order and length of the block segments.     

Synthesis and self-assembly of a new amphiphilic thermosensitive poly(N-vinylcaprolactam)/poly(ε-caprolactone) block copolymer

New amphiphilic thermosensitive poly(N-vinylcaprolactam)/poly(ε-caprolactone) (PNVCL-b-PCL) block copolymers were synthesized by ring-opening polymerization of ε-caprolactone with hydroxy-terminated poly(N-vinylcaprolactam) (PNVCL-OH) as a macroinitiator. The structures of the polymers were confirmed by IR, ¹H NMR and GPC. The critical micelle concentrations of copolymer in aqueous solution measured by the fluorescence probe technique reduced with the increasing of the proportion of hydrophobic parts, so did the diameter and distribution of the micelles determined by dynamic light scattering. The shape observed by transmission electron microscopy (TEM) demonstrated that the micelles are spherical. On the other hand, the UV–vis measurement showed that polymers exhibit a reproducible temperature-responsive behavior with a lower critical solution temperature (LCST). The LCST of PNVCL-OH can be adjusted by controlling the molecular weights, and that of copolymers can be adjusted by controlling the compositions and the concentration. Variable temperature TEM measurements demonstrated that LCST transition was the result of transition of individual micelles to larger aggregates.     

Synthesis and micellization of an amphiphilic biodegradable β-cyclodextrin/poly(γ-benzyl L-glutamate) copolymer

β-Cyclodextrin/poly(γ-benzyl L-glutamate) (β-CD-PBLG) copolymers were synthesized by ring-opening polymerization of N-carboxy-γ-benzyl L-glutamate anhydride (BLG-NCA) in N,N-dimethylformamide(DMF) initiated by mono-6-amino-β-cyclodextrin(H₂N-β-CD). The structures of the copolymers were determined by IR, ¹H NMR and GPC. The fluorescence technique was used to determine the critical micelle concentration (CMC) of copolymer micelle solution. The diameter and the distribution of micelles were characterized by dynamic light scattering(DLS) and its shape was observed by transmission electron microscopy(TEM). The results showed that BLG-NCA could be initiated by H₂N-β-CD to produce copolymer. These copolymers showed an amphiphilic nature and could self-assemble into nano-micelles in water. The CMC of copolymer solution and the size of micelle reduced with the increasing of the proportion of hydrophobic parts. TEM images demonstrated the micelles are all spherical. Such copolymers could be expected to find applications in drug delivery systems and other biomedical domains.     

PTPFCBBMA-b-PEG-b-PTPFCBBMA amphiphilic triblock copolymer: Synthesis and self-assembly behavior

We present the synthesis and self-assembly behavior of a new semi-fluorinated amphiphilic triblock copolymer. A series of perfluorocyclobutyl aryl ether-based amphiphilic ABA triblock copolymer containing hydrophilic poly(ethylene glycol) segment as the middle block were synthesized by atom transfer radical polymerization (ATRP). ATRP of 4-(4′-p-tolyloxyperfluorocyclobutoxy)benzyl methacrylate was initiated by PEG-based bifunctional macroinitiators with different molecular weights to obtain the desired copolymers with narrow molecular weight distributions (M_w/M_n ≤ 1.30) and the number of perfluorocyclobutyl linkage can be tuned by the feed ratio and the conversion of the fluorine-containing methacrylic monomer. The critical micelle concentrations of these amphiphilic ABA triblock copolymers in aqueous media were determined by fluorescence probe technique. They could aggregate to form spherical and cylindrical micelles visualized by TEM with varying the content of hydrophobic segment.     

Fabrication of star-shaped, thermo-sensitive poly(N-isopropylacrylamide)-cholic acid-poly(?-caprolactone) copolymers and their self-assembled micelles as drug carriers

Novel star-shaped copolymers, comprised of a thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAm) segment and three hydrophobic poly(?-caprolactone) (PCL) arms were fabricated. The copolymers were prepared by stannous octoate (Sn(Oct)₂) catalyzed ring-opening polymerization of ?-caprolactone (CL) using cholic acid functionalized PNIPAAm as the macroinitiator. The lower critical solution temperatures (LCST) of the copolymer solutions are attractively close to the nominal physiologic temperature at around 37 °C. The in vitro cytotoxicity test indicated no apparent cytotoxicity. The amphiphilic star-shaped copolymers were capable of self-assembling into spherical micelles in water at room temperature, and they possessed low critical micelle concentrations (CMCs) of 3 ∼ 8 mg/L in aqueous solution determined by fluorescence spectroscopy using pyrene as a probe. Transmission electron microscopy (TEM) measurement showed that the micelles exhibited a spherical shape with a size range of 30 ∼ 75 nm in diameter. In addition, the anticancer drug, methotrexate (MTX) can be loaded effectively in the polymeric micelles and its release was temperature-stimulated, which suggests that these materials have good potential as “intelligent” drug carriers.     

Self-assembly of thermo-responsive poly(oligo(ethylene glycol) methyl ether methacrylate)-C60 in water-methanol mixtures

Well-defined statistical copolymer of poly (di(ethylene glycol) methyl ether methacrylate-stat-oligo(ethylene glycol) methyl ether methacrylate-C₆₀ ((PMEO₂MA-stat-POEGMA₃₀₀)-C₆₀) was synthesized via atom transfer radical polymerization (ATRP) reaction and atom transfer radical addition (ATRA) processes. The lower critical solution temperature (LCST) of PMEO₂MA-stat-POEGMA₃₀₀ increased from 42 to 95 °C when the amounts of methanol was increased from 0 to 30 vol%, beyond which the LCST could not be quantified. Similarly, the LCST of (PMEO₂MA-stat-POEGMA₃₀₀)-C₆₀ also increased with methanol content, however it was lower than PMEO₂MA-stat-POEGMA₃₀₀ for all methanol/water compositions. The CMC of (PMEO₂MA-stat-POEGMA₃₀₀)-C₆₀ increased with increasing methanol content, suggesting that methanol is a better solvent for PMEO₂MA-stat-POEGMA₃₀₀ segment. The amphiphilic (PMEO₂MA-stat-POEGMA₃₀₀)-C₆₀ structure formed spherical micelles in water/methanol mixture, and larger micelles were formed at higher methanol content. The hydrodynamic radius (R_h) remained constant at temperature below the LCST. It increased dramatically at temperature greater than the LCST, and the (R_g/R_h) increased from ∼0.75 to ∼1.0. We believe that the (PMEO₂MA-stat-POEGMA₃₀₀) coronas dehydrate at higher temperature, and the micelles associate to form larger aggregates. In water/methanol mixtures, core-shell micelles and large compound micelles are produced below and above the LCST respectively.     

Synthesis and characterization of amphiphilic PLA-(PαN3CL-g-PBA) copolymers by ring-opening polymerization and click reaction

The present study prepared novel amphiphilic block-graft PDLLA-b-(PαN₃CL-g-PBA) and PLLA-b-(PαN₃CL-g-PBA) functional polyesters, containing a hydrophilic poly(α-azido-ε-caprolactone-graft-alkyne) (PαN₃CL-g-alkyne) segment and a hydrophobic poly(dl-lactide) (PDLLA) or poly(l-lactide) (PLLA) segment, using ring-opening polymerization of α-chloro-ε-caprolactone (αClCL) with a hydroxyl-terminated macroinitiator of PDLLA or PLLA, substituting pendent chloride with sodium azide. The copolymers were subsequently used for grafting of 2-propynyl-terminal benzoate moieties by way of Cu(I)-catalyzed Huisgen's 1,3-dipolar cycloaddition, thus producing a “click” reaction. Differential scanning calorimetry (DSC) and ¹H NMR, FT-IR, and GPC examined the characteristics of the copolymers. The critical micelle concentration (CMC) ranged from 2.7 mg L^?1 to 24.6 mg L^?1 at 25 °C and the average micelle size ranged from 106 nm to 297 nm. The length of the hydrophilic segment and the configuration of the lactide both influenced micelle stability. The micelle of PLLA-b-(PαN₃CL-g-PBA) provided high drug entrapment efficiency and loading content. The results from in vitro cell viability assays indicated that PLA-b-(PαN₃CL-g-PBA) shows low cytotoxicity.     

Thermoresponsive core-shell-corona micelles of poly(ethyleneglycol)-b-poly(N-isopropylacrylamide)-b-polystyrene

Core-shell-corona micelles with a thermoresponsive shell self-assembled by triblock copolymer of poly(ethyleneglycol)-b-poly(N-isopropylacrylamide)-b-polystyrene (PEG₄₅-b-PNIPAM₁₆₈-b-PS₄₆) are studied by ¹H NMR, light scattering and atomic force microscopy. The thermoresponsive triblock copolymer, which has a relatively short hydrophobic PS block, can disperse in water at room temperature to form core-shell-corona micelles with the hydrophobic PS block as core, the thermoresponsive PNIPAM block as shell and the hydrophilic PEG block as corona. At temperature above lower critical solution temperature (LCST) of the PNIPAM block, the PNIPAM chains gradually collapse on the PS core to shrink the size and change the structure of the resultant core-shell-corona micelles with temperature increasing. It is found that there possibly exists an interface between the PNIPAM shell and PEG corona of the core-shell-corona micelles at temperature above LCST of the PNIPAM block.     

Synthesis and thermal responsive properties of P(LA-b-EO-b-PO-b-EO-b-LA) block copolymers with short hydrophobic poly(lactic acid) (PLA) segments

Poly(lactic acid) (PLA) was successfully grafted to both ends of Pluronic F87 block copolymer (PEO-PPO-PEO) to obtain amphiphilic P(LA-b-EO-b-PO-b-EO-b-LA) block copolymers (PLA-F87-PLA) with short PLA blocks. The block composition and structure of PLA-F87-PLA block copolymers were studied by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), differential scanning calorimetric (DSC) and wide angle X-ray diffraction (WXRD) techniques. The aggregation behavior of PLA-F87-PLA block copolymers in aqueous solutions was studied using the laser light scattering (LLS) technique. Various types of particles consisting of small micelles, medium and large aggregates were observed due to the complex structure of these copolymers. Importantly, PLA-F87-PLA block copolymers retain the thermal responsive behavior found in Pluronic systems. The critical micellization temperatures (CMTs) of PLA-F87-PLA were lower than that of F87 because of increased hydrophobicity introduced by the PLA blocks. A reversible sol-gel transition was observed for the hydrogels formed from PLA₆-F87-PLA₆ and PLA₉-F87-PLA₉ block copolymers. Preliminary results from the drug release study using a hydrophilic model drug procain hydrochloride (PrHy) were promising. Constant initial release rate was observed.     

Synthesis and properties of amphiphilic thermo-sensitive block copolymers

Octadecyl acrylate (ODA) as hydrophobic monomer and N-isopropylacryamide (NIPAAm) as hydrophilic monomer were chosen to synthetize the thermo-sensitive block copolymers PODA_x-PNIPAAm_y-PODA_x (BAB-type) via reversible-addition-fragmentation chain transfer (RAFT) polymerization, the block copolymers could self-assemble to flower-like micelles in aqueous solution with hydrophobic PODA as the inner core and stabilized by hydrophilic PNIPAAm as the outer shell. The characterizations of the micelles such as surfactivity, thermo-sensitivity, micelle hydrodynamic radius (R _h ) and polydispersity index (PdI) were demonstrated by surface tension technique, UV-Vis, and dynamic light scattering (DLS) measurements, respectively. The longer the hydrophilic chain was, the higher the critical micellization concentration (CMC) would be, and the higher content of the PODA was, the lower the lower critical solution temperature (LCST) would be. The average R _h remained at about 100 nm below LCST, but decreased sharply to about 42 nm and kept constant when reaching and above LCST, which meant the non-aggregation of BAB type block copolymers. The micelle was homogeneous with the small PdI within the range of research. B_0.5mA_24mB_0.5m had the largest capacity to encapsulate lipophilic Sudan Red IV model drugs and the drug loading efficiency was 9.76%.     

Comparison of micelles formed by amphiphilic poly(ethylene glycol)‐b‐poly(trimethylene carbonate) star block copolymers

In this article, we describe the synthesis and solution properties of PEG‐b‐PTMC star block copolymers via ring‐opening polymerization (ROP) of trimethylene carbonate (TMC) monomer initiated at the hydroxyl end group of the core PEG using HCl Et₂O as a monomer activator. The ROP of TMC was performed to synthesize PEG‐b‐PTMC star block copolymers with one, two, four, and eight arms. The PEG‐b‐PTMC star block copolymers with same ratio of between hydrophobic PTMC and hydrophilic PEG segments were obtained in quantitative yield and exhibited monomodal GPC curves. The amphiphilic PEG‐b‐PTMC star block copolymers formed spherical micelles with a core–shell structure in an aqueous phase. The mean hydrodynamic diameters of the micelles increased from 17 to 194 nm with increasing arm number. As arm number increased, the critical micelle concentration (CMC) of the PEG‐b‐PTMC star block copolymers increased from 3.1 × 10^?3 to 21.1 × 10^?3 mg/mL but the partition equilibrium constant, which is an indicator of the hydrophobicity of the micelles of the PEG‐b‐PTMC star block copolymers in aqueous media, decreased from 4.44 × 10⁴ to 1.34 × 10⁴. In conclusion, we confirmed that the PEG‐b‐PTMC star block copolymers form micelles and, hence, may be potential hydrophobic drug delivery vehicles. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Rational design,syntheses, characterization and solution behavior of amphiphilic azobenzene-containing linear-dendritic block copolymers

In this paper, based on the synthesis of precursor linear-dendritic block copolymers (LDBCs) with a linear poly(ethylene glycol) (PEG) block of molecular weight around 2000 and dendritic polyamidoamine (PAMAM) segments of generation G0 to G3, a series of azobenzene-containing amphiphilic LDBCs mPEG-dendr[PAMAM-(AZO)_n] (n = 2, 4, 8, 16) have been successfully prepared in moderate yields 45–60%, through complete Michael addition between the peripheral amine groups of dendritic segment and the reactive azobenzene acrylate mesogen units bearing octyloxy tails and flexible decylmethylene spacers. The purified copolymers have been characterized and confirmed by NMR, FT-IR, MALDI-TOF MS, and GPC showing narrow molecular weight distribution in the range 1.09–1.20. A generation-dependent polymeric micellar aggregation behavior of thus obtained amphiphilic LDBCs from nanofibers of uniform diameter around 20 nm to nanospheres/oval sheets, vesicles, and porous large compound micelles (LCMs) of micrometer size has been demonstrated in selective solvent mixture of dioxane/water. Furthermore, photoisomerization transformation of these azobenzene-containing LDBCs and their kinetics of reversible trans-cis-trans photochemical transitions in THF solution have also been investigated, the measured trans-cis photoisomerization rate constant 0.0240 s^?1 for G3 copolymer is twice of the 0.0127 s^?1 determined for the precursor azobenzene compound, manifesting a kind of promising photoresponsive copolymer materials.