Double-responsive core-shell-corona micelles from self-assembly of diblock copolymer of poly(t-butyl acrylate-co-acrylic acid)-b-poly(N-isopropylacrylamide)

Self-assembly of poly(t-butyl acrylate-co-acrylic acid)-b-poly(N-isopropylacrylamide) [P(tBA-co-AA)-b-PNIPAM], which was obtained from part hydrolysis of PtBA-b-PNIPAM synthesized by sequential atom transfer radical polymerization (ATRP) was studied. Thermo- and pH-responsive core-shell-corona (CSC) micelles with different structures were formed from (PtBA-co-PAA)-b-PNIPAM in aqueous solution. At pH 5.8 and 25 °C, the block copolymer self-assembled into spherical core-shell micelles with hydrophobic PtBA segments as the core, hydrophilic PAA/PNIPAM segments as the mixed shell. Increasing temperatures, core-shell micelles converted into CSC micelles with PtBA as the core, collapsed PNIPAM as the shell and soluble PAA as the corona. Moreover, decreasing pH at 25 °C, PAA chains collapsed onto the core resulting in CSC micelles with PtBA as the core, PAA as the shell and PNIPAM as the corona.     

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.     

Temperature-responsive multilayered micelles formed from the complexation of PNIPAM-b-P4VP block-copolymer and PS-b-PAA core–shell micelles

Multilayered micelles with a polystyrene (PS) core, a swollen poly(acrylic acid) (PAA)/poly(4-vinyl pyridine) (P4VP) complex shell and a poly(4-vinyl pyridine)-block-poly(isopropyl acryl amide) (P4VP-b-PNIPAM) block-copolymer corona was synthesized by complexation between PNIPAM₅₃-b-P4VP₁₀₉ block-copolymers and the PS₁₂₀-b-PAA₄₇ diblock-copolymer core–shell micelles in ethanol due to the hydrogen bonding between the AA units and 4VP units. The surface of the micelle has been modified and a temperature sensitive block PNIPAM was introduced into the corona of the micelles. After being dialyzed against acidic water, PNIPAM corona would collapse onto the PAA/P4VP shell and the excessive P4VP shell would extend into the acidic solution to form the corona reversed micelles when the micelle aqueous solution was heated to 45 °C. The whole process was performed using dynamic light scattering (DLS), static light scattering (SLS), atom force microscope (AFM) and nuclear magnetic resonance (NMR).     

Thermosensitive poly(N-isopropylacrylamide) nanocapsules with controlled permeability

In this paper, novel thermosensitive poly(N-isopropylacrylamide) (PNIPAM) nanocapsules with temperature-tunable diameter and permeability are reported. Firstly, the core-shell composite microparticles were synthesized by precipitation polymerization with isothiocyanate fluorescein (FITC) entrapped SiO₂ as core and cross-linked PNIPAM as shell. Then, the SiO₂ core was etched by hydrofluoric acid at certain condition and the pre-trapped FITC molecules remained within the inner cavity. The FITC release profile and TEM studies clearly indicate that the release behavior of FITC could be controlled effectively by the external temperature. Above the LCST of PNIPAM (32 °C), the dehydrated PNIPAM shell inhibited the release of FITC from the internal cavity while below its LCST, the fluorophore could permeate the swollen shell easily.     

Shell-core-corona aggregates formed from poly(styrene)-poly(4-vinylpyridine) block copolymer induced by added homopolymer via interpolymer hydrogen-bonding

The solution behavior of poly(styrene)-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer with added poly(4,4′-oxydiphenylenepyromellitamic acid) (POAA) homopolymer in DMF is studied by dynamic light scattering (DLS), nuclear magnetic resonance (NMR), and transmission electron microscopy (TEM). It is found that coaggregation takes place when mixing PS-b-P4VP block copolymer and POAA homopolymer in DMF due to the strong interpolymer hydrogen-bonding between POAA chains and P4VP blocks. The coaggregation is a diffusion-controlled process and the complexation-induced aggregates are very stable. NMR measurements demonstrate that the resultant aggregates are much more swollen compared with typical amphiphilic block copolymer core-shell micelles. DLS measurements with Eu³⁺ as a probe combined with TEM observation, are employed to study the structure of the aggregates. Results reveal that the formed aggregates are core-shell spheres with the P4VP/POAA complexes as core and the PS blocks as shell when the weight ratio of POAA to PS-b-P4VP is lower. However, a core-shell-corona structure forms with a thin layer of POAA chains adsorbed on the initial core-shell aggregates with increasing weight content of POAA to 60%. Finally, possible mechanisms of the structural transitions are proposed.     

Nanostructure and hydrogen bonding in interpolyelectrolyte complexes of poly(?-caprolactone)-block-poly(2-vinyl pyridine) and poly(acrylic acid)

Nanostructured poly(?-caprolactone)-block-poly(2-vinyl pyridine) (PCL-b-P2VP)/poly(acrylic acid) (PAA) interpolyelectrolyte complexes (IPECs) were prepared by casting from THF/ethanol solution. The morphological behaviour of this amphiphilic block copolymer/polyelectrolyte complexes with respect to the composition was investigated in a solvent mixture. The phase behaviour, specific interactions and morphology were investigated using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, optical microscopy (OM), dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelle formation occurred due to the aggregation of hydrogen bonded P2VP block and polyelectrolyte (PAA) from non-interacted PCL blocks. It was observed that the hydrodynamic diameter (D_h) of the micelles in solution decreased with increasing PAA content up to 40 wt%. After 50 wt% PAA content, D_h again increased. The micelle formation in PCL-b-P2VP/PAA IPECs was due to the strong intermolecular hydrogen bonding between PAA homopolymer units and P2VP blocks of the block copolymer. The penetration of PAA homopolymers into the shell of the PCL-b-P2VP block copolymer micelles resulted in the folding of the P2VP chains, which in turn reduced the hydrodynamic size of the micelles. After the saturation of the shell with PAA homopolymers, the size of the micelles increased due to the absorption of added PAA onto the surface of the micelles.     

pH/temperature sensitive poly(ethylene glycol)-based biodegradable polyester block copolymer hydrogels

Novel pH and temperature sensitive biodegradable block copolymers composed of poly(ethylene glycol) (PEG), polyglycolide (GA), ?-caprolactone (CL) and sulfamethazine oligomers (OSMs) were synthesized by ring opening polymerization and 1,3-dicyclohexyl-carbodiimide (DCC) mediated coupling reactions. Their physicochemical properties in aqueous media were characterized by ¹H NMR spectroscopy and gel permeation spectroscopy. The sol-gel phase transition behavior of OSM-PCGA-PEG-PCGA-OSM block copolymers was investigated both in solution and injection to PBS buffer at pH 7.4 and 37 °C. Aqueous solutions of OSM-PCGA-PEG-PCGA-OSM changed from a sol to a gel phase with increasing temperature and decreasing pH. The sol-gel transition properties of these block copolymers are influenced by the hydrophobic/hydrophilic balance of the copolymers, block length, hydrophobicity, stereoregularity of the hydrophobic components within the block copolymer, and the ionization of the pH functional groups in the copolymer, which depends on the environmental pH. Degradation of the triblock and pentablock copolymers at 37 °C (pH 7.4), and at 0 °C and 5 °C both at pH 8.0, was investigated. It was demonstrated here using the in vitro test method, that the anticancer agent paclitaxel (PTX) could be loaded and released by the pH and temperature sensitive OSM-PCGA-PEG-PCGA-OSM block copolymer, such that this could be used as a suitable matrix for subcutaneous injection in drug delivery systems.     

Synthesis and characterization of dual stimuli-responsive block copolymers based on poly(N-isopropylacrylamide)-b-poly(pseudoamino acid)

The current study synthesized amphiphilic thermal/pH-sensitive block copolymers PNiPAAm-b-PHpr by condensation polymerization of trans-4-hydroxy-l-proline (Hpr) initiated from hydroxy-terminated poly(N-isopropylacrylamide) (PNiPAAm) as the macroinitiator in the presence of the catalyst, SnOct₂. ¹H NMR, FTIR, and gel permeation chromatography (GPC) characterized these copolymers. Their solutions showed reversible changes in optical properties: transparent below a lower critical solution temperature (LCST) and opaque above the LCST. The LCST values depended on the polymer composition and the media. With critical micelle concentrations (CMCs) in the range of 1.23-3.73 mg L⁻¹, the block copolymers formed micelles in the aqueous phase owing to their amphiphilic characteristics. Increased hydrophobic segment length or decreased hydrophilic segment length in an amphiphilic diblock copolymer produced lower CMC values. The current work proved the core-shell structure of micelles by ¹H NMR analyses of the micelles in D₂O. Transmission electron microscopy analyzed micelle morphology, showing a spherical core-shell structure. The micelles had an average size in the range of 170˜210 nm (blank), and 195˜280 nm (with drug). Observations showed high drug entrapment efficiency and drug-loading content for the drug micelles.     

Injectable hydrogels of poly(?-caprolactone-co-glycolide)-poly(ethylene glycol)-poly(?-caprolactone-co-glycolide) triblock copolymer aqueous solutions

Thermogelling triblock copolymers of poly(?-caprolactone-co-glycolide)-poly(ethylene glycol)-poly(?-caprolactone-co-glycolide) [P(CL-GA)-PEG-P(CL-GA)] were successfully prepared by control of the hydrophilicity/hydrophobicity balance and chemical compositions of the copolymers. The aqueous solutions of the copolymers underwent sol-gel transition as the temperature was increased from 20 to 60 °C. The amphiphilic copolymer formed micelles in water and a gel was formed by aggregation of micelles. The structure parameters played a critical role in determining sol-gel transition behavior. Either increasing [GA]/[CL] ratio or decreasing P(CL-GA) block length could induce the increase of the lower sol-gel transition temperature. Glycolide (GA) was incorporated into the polymer chain to increase the polymer degradation rate. Sustained release of rifampicin for approximately 32 days was obtained from the gel. It is believed to have potential applications in drug delivery and tissue engineering.     

Copolymer hydrogels based on N-isopropylacrylamide and itaconic acid

In this study, the swelling behaviour of copolymer hydrogels of N-isopropylacrylamide (NIPAM) and itaconic acid (IA) in response to temperature and pH value of the external media was studied. The equilibrium degree of swelling for PNIPAM and PNIPAM/IA copolymers was greater at 25 °C than at 37 °C. The degree of swelling was low at low pH values. As the degree of ionization increased above the nominal pK_a values of IA, the increased hydrophilicity resulted in larger degrees of swelling. At 37 °C, the PNIPAM hydrogel and some copolymers show anomalous swelling behaviour, i.e. the overshooting effect, in buffered solutions of certain pH values. A swelling-deswelling study showed that the deswelling process of the hydrogels was faster then the swelling process. According to dynamic swelling studies, the diffusion exponent and the diffusion coefficient both increase with increasing content of IA.     

The effects of the selectivity of the toluene/ethanol mixture on the micellar and the ordered structures of an asymmetric poly(styrene-b-4-vinylpyridine)

The effects of the solvent selectivity of toluene/ethanol mixtures on the micellar and ordered structures of an asymmetric diblock copolymer of PS(19.6 K)-b-P4VP(5.1 K) in the dilute (1 wt%) and semi-dilute (8 wt%) solutions, as well as in the gel and solid films, were studied using small angle X-ray scattering (SAXS), generalized indirect Fourier transform (GIFT), and transmission electron microscopy (TEM) methods. The solvent selectivity was controlled by ? (weight percentage of ethanol in toluene/ethanol mixture). Individual micelles, space-filled micellar structure (without three-dimensional order), and three-dimensionally ordered gel and solid structures were observed from the 1 and 8 wt% solutions, the gel, and the solid film, respectively. In the 1 wt% solution, the individual micellar structures were strongly dependent on ?; the spherical micelles with P4VP core at ? = 0, the unimer state at 10 ≤ ? ≤ 50, the spherical micelles with PS core at ? = 60, the cylindrical micelles with PS core at ? = 70 and 80, and precipitation at ? = 90 and 100 were observed. The 8 wt% solution was close to overlap concentration with the unimer state in the regions of 20 ≤ ? ≤ 40. In the gel, the ordered structure was observed in the sequence of bcc, hexagonal, gyroid, lamellar, reverse hexagonal and random as ? increased, and could be explained by the change of the relative volume fraction of each block as ? changed, similar to the phase sequence in the phase diagram of the diblock copolymer. The solid films showed the various kinetically frozen ordered microstructures such as randomly packed sphere, hexagonal, gyroid, hexagonally perforated lamella, reversed hexagonal, and randomly packed cylinder, which were controlled by the solvent quality in the gel before solidification. We believe that these results can be applied to photonic crystals, self-assembled nano-patterning, and functional nanoparticles in which the structural control is most important.     

Exfoliation of organoclay nanocomposites based on polystyrene-block-polyisoprene-block-poly(2-vinylpyridine) copolymer: Solution blending versus melt blending

Exfoliated nanocomposites based on polystyrene-block-polyisoprene-block-poly(2-vinylpyridine) (SI2VP triblock) copolymer were prepared by solution blending and melt blending. Their dispersion characteristics were investigated using transmission electron microscopy, X-ray diffraction, and small-angle X-ray scattering (SAXS). For the study, SI2VP triblock copolymers with varying amounts of poly(2-vinylpyridine) (P2VP) block (3, 5, and 13 wt%) and different molecular weights were synthesized by sequential anionic polymerization. In the preparation of nanocomposites, four different commercial organoclays, treated with a surfactant having quaternary ammonium salt, were employed. It was found from SAXS that the microdomain structure of an SI2VP triblock copolymer having 13 wt% P2VP block (SI2VP-13) transformed from core-shell cylinders into lamellae when it was mixed with an organoclay. It was found further that the solution-blended nanocomposites based on a homogeneous SI2VP triblock copolymer having 5 wt% P2VP block (SI2VP-5) gave rise to an exfoliated morphology, irrespective of the differences in chemical structure of the surfactant residing at the surface of the organoclays, which is attributable to the presence of ion-dipole interactions between the positively charged N⁺ ion in the surfactant residing at the surface of the organoclay and the pyridine rings in the P2VP block of SI2VP-5 and SI2VP-13, respectively. Both solution- and melt-blended nanocomposites based on microphase-separated SI2VP-13 having an order-disorder transition temperature (T_ODT) of approximately 210 °C also gave rise to exfoliated morphology. However, melt-blended nanocomposite based on a high-molecular-weight SI2VP triblock copolymer having a very high T_ODT (estimated to be about 360 °C), which was much higher than the melt blending temperature employed (200 °C), gave rise to very poor dispersion of the aggregates of organoclay. It is concluded that the T_ODT of a block copolymer plays a significant role in determining the dispersion characteristics of organoclay nanocomposites prepared by melt blending.     

Synthesis and self-assembly of amphiphilic poly(acrylic acid-b-dl-lactide) to form micelles for pH-responsive drug delivery

An amphiphilic diblock copolymer of poly(acrylic acid-b-dl-lactide) (PAAc-b-PDLLA) was synthesized by ring-opening polymerization of dl-lactide initiated by hydroxyl-terminated polyacrylic acid (PAAc-OH). The critical micelle concentration (CMC) of PAAc-b-PDLLA in aqueous solution, determined by fluorescence spectroscopy using pyrene as a probe, was found about 80 mg L⁻¹. A solution of PAAc-b-PDLLA in tetrahydrofuran (THF) was dialyzed against pure water to form pH-responsive micelles. Transmission electron microscopy (TEM) measurement showed that the micelles exhibited regular spherical morphology and the diameters of particles were in the range from 40 to 90 nm. The micelles were stable at a pH above 3 or at an ionic strength below 1.0, however, they aggregated and precipitated in the solutions when further decreasing pH or increasing ionic strength. Prednisone acetate, as a model hydrophobic drug, was loaded into the polymeric micelles. In vitro release of prednisone acetate from polymeric micelles showed that the release kinetics was strongly pH-dependent. Hydrophobic drug displayed “burst” release at pH 7.4, while only a small part of loaded drug released at pH 1.4. This provides a new choice to design delivery system for the gastrointestinal tract (GI tract), where the pH environment is strongly acidic in stomach and basic in intestine. The cytotoxicity measurement by MTT assay indicated that PAAc-b-PDLLA was low toxic in HeLa cells with an IC50 value of 2.8 mg mL⁻¹, which suggests that PAAc-b-PDLLA could be used as a safe candidate for pH-responsive drug delivery.     

Dual thermo- and pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid) hydrogels with rapid response behaviors

Novel dual temperature- and pH-sensitive comb-type grafted poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-co-AAc)) hydrogels were successfully prepared by grafting PNIPAM chains with freely mobile ends onto the backbone of a cross-linked P(NIPAM-co-AAc) network. The prepared comb-type grafted P(NIPAM-co-AAc) hydrogels exhibited a more rapid deswelling rate than normal-type P(NIPAM-co-AAc) hydrogels in ultrapure water in response to abrupt changes from 25 °C to 60 °C. The same was true in buffer solution with a pH jump from 7.4 to 2.0 at 25 °C. Unexpectedly, the comb-type grafted P(NIPAM-co-AAc) hydrogels showed abnormal shrinkage behaviors in a buffer solution when the temperature increased from 25 °C to 60 °C with a pH value fixed at 7.4 or 2.0. In a buffer solution of pH 7.4, when the environmental temperature jumped from 25 °C to 60 °C, the grafted comb-type hydrogels shrank slower than the normal-type hydrogels, while at pH 2.0, the gels shrank faster than the normal-type gels in the beginning, which was followed by a slower shrinking. Interestingly, the much quicker shrinkage of the comb-type grafted P(NIPAM-co-AAc) hydrogels was observed because of the cooperative thermo-/pH-responses when the simultaneous temperature and pH stimuli met from pH 7.4/25 °C to pH 2.0/60 °C. The results of this study provide valuable information regarding the development of dual stimuli-sensitive hydrogels with fast responsiveness.     

Self-assembling of star-like amphiphilic block copolymers with polyelectrolyte blocks. Effect of pH

The self-assembling behaviour of a four-arm amphiphilic star block copolymer, (PMMA₇₃-b-PAA₁₄₃)₄, with poly(methyl methacrylate) inner blocks and poly(acrylic acid) outer blocks in ratio 1:2 (PMMA:PAA) has been investigated in aqueous solutions as a function of pH by dynamic light scattering and cryo-transmission electron microscopy. At low pH (pH ≤ 5) the amphiphile forms in the presence of salt both spherical and worm-like micellar aggregates that coexist in solution. At high pH (pH > 12) the solution contains mainly spherical micelles and a small number of larger aggregates that have ‘pearl-necklace’ structure, indicating the disintegration of the worm-like species. In addition to the experiments, computer simulations of the four-arm amphiphilic star block copolymer with the same ratio of the blocks as above were conducted using a coarse-grained model. The simulations predict the formation of the worm-like micellar aggregates at low pH and the spherical ones at high pH. The changes in the morphology of the aggregates are related to the higher degree of ionization of poly(acrylic acid) blocks at high pH and to the swelling of the corona of the micelles by the higher osmotic pressure due to trapped counterions.     

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.     

Preparation of hydrogel nanoparticles by atom transfer radical polymerization of N-isopropylacrylamide in aqueous media using PEG macro-initiator

PEG-b-PNIPAM block copolymers are synthesized by the atom transfer radical polymerization of NIPAM using PEG macro-initiator. When the polymerization temperature is 25 °C, the block copolymer is soluble in water, whereas the block copolymer is phase-separated to form micelles during polymerization as the polymerization temperature is raised to 50 °C, the temperature above the LCST of PEG-b-PNIPAM. To prepare stable hydrogel nanoparticles in water at room temperature, a small amount of N,N′-ethylenebisacrylamide is added as a cross-linker to the reaction system, where the size of nanoparticles is controlled by the composition of mixed solvent.     

Doubly thermo-responsive brush-linear diblock copolymers and formation of core-shell-corona micelles

Doubly thermo-responsive brush-linear diblock copolymer of poly[poly(ethylene glycol) methyl ether vinylphenyl]-block-poly(N-isopropylacrylamide) (PmPEGV-b-PNIPAM) is prepared by RAFT polymerization. The obtained brush-linear diblock copolymer exhibits two lower critical solution temperatures (LCSTs) corresponding to the linear poly(N-isopropylacrylamide) (PNIPAM) block and the brush poly[poly(ethylene glycol) methyl ether vinylphenyl] (PmPEGV) block in water. This brush-linear diblock copolymer undergoes a two-step temperature sensitive micellization. At temperature above the first LCST, the brush-linear diblock copolymer self-assembles into core-corona micelles with the dehydrated PNIPAM block forming the core and the solvated brush PmPEGV block forming the corona. When temperature increases above the second LCST, the polystyrene backbone in the brush PmPEGV block collapses onto the dehydrated PNIPAM core to form core-shell-corona micelles, in which the dehydrated PNIPAM block forms the core, the collapsed polystyrene backbone in the brush PmPEGV block forms the shell and the solvated poly(ethylene glycol) side-chains forms the corona. The effect of the length of the PNIPAM block and the length of the poly(ethylene glycol) side-chains on the thermo-responsive micellization and the size of core-shell-corona micelles is investigated.     

pH- and thermo-multi-responsive fluorescent micelles from block copolymers via reversible addition fragmentation chain transfer (RAFT) polymerization

Well-defined pH- and thermo- multi-responsive fluorescent micelles based on the self-assembly of diblock copolymers poly[(N-isopropyl-acrylamide-co-N-vinylcarbazole)-b-2-(dimethylamino)ethyl acrylate], (PNIPAAM-co-PNVC)-b-PDMAEA, are described. The diblock copolymers are prepared via the reversible addition fragmentation chain transfer (RAFT) copolymerization of N-isopropyl-acrylamide (NIPAAM) and N-vinylcarbazole (NVC) followed by chain extension in presence of 2-(dimethylamino)ethyl acrylate) (DMAEA). The micelles are formed in aqueous solutions in a wide range of temperature (25-60 °C), and their sizes increase from 40 to 65 nm when varying pH from basic to acidic. The cross-linking of the PDMAEA-containing shell with 1,2-bis(2-iodoethoxy)ethane (BIEE) results in spherical soft nanoparticles which size is increased by 20-25% when compared to the micelles. The presence of NVC in concentrations as low as 4% in the core of the micelles allow the nanoparticles to be tagged by fluorescence, making them well suited for therapeutic applications.     

Synthesis of cationic poly(methyl methacrylate)-poly(N-isopropyl acrylamide) core-shell latexes via two-stage emulsion copolymerization

Thermally sensitive poly(methyl methacrylate (MMA))-poly(N-isopropylacrylamide (NIPAM)) core-shell particles were prepared via a two-stage emulsion copolymerization process. Methylene bisacrylamide (MBA), 2,2′-azobis (2-amidinopropane) dihydrochloride (V50) and dodecylethyl dimethyl ammonium bromide (DEDAB) were used as crosslinker, cationic initiator and surfactant, respectively. Functional core-shell particles were prepared using aminoethyl methacrylate hydrochloride (AEMH) as cationic co-monomer to increase the surface charge density. The influences of the crosslinker and co-monomer concentrations on the thickness and swelling capacity of the PNIPAM-based shell layer were studied. The latex particle size and particle size distribution were determined both by dynamic light scattering (DLS) and scanning electron microscopy (SEM). Monodisperse particles were produced with diameters between 150-250 nm (at 25 °C) and 140-190 nm (at 50 °C). The surface charge density was determined by chemical titration and higher values (∼10 μmol/g) were obtained for the functional core-shell particles. The electrokinetic properties of the dispersions at several pH and temperature values confirm the presence of the shell layer and cationic surface charges.