Thermoresponsive Behavior Research Articles

Probing Thermoresponsive Polymerization-Induced Self-Assembly with Variable-Temperature Liquid-Cell Transmission Electron Microscopy

Summary We directly initiate and visualize the formation of polymeric nanomaterials via variable-temperature liquid-cell transmission electron microscopy (VT-LCTEM). With temperature control in the liquid cell, reversible addition-fragmentation chain transfer polymerization was thermally initiated, leading to the formation of amphiphilic block copolymers that assemble upon dispersion polymerization-induced self-assembly (PISA). In combination with traditional ex situ analyses, VT-LCTEM enabled not only the characterization of the nanoparticles in situ but also the observation of a thermal phase transition. Critically, because these assemblies form from thermoresponsive components, any temperature changes during sample preparation and analysis can alter morphologies, necessitating direct in situ characterization of reaction progression. We believe that the findings and the technique described herein will lead to unprecedented possibilities for the development and characterization of self-organizing soft matter.

Sulfobetaine-based polydisulfides with tunable upper critical solution temperature (UCST) in water alcohols mixture, depolymerization kinetics and surface wettability

HypothesisSynthesis of a new family of polymers having a polydisulfide structure can be conducted from sulfobetaine-based derivative of natural (R)-lipoic acid. A polydisulfide backbone of polymer can be depolymerized by response to external stimuli and sulfobetaine pendant groups ensure the upper critical solution temperature (UCST) behaviour temperatures that can be modulated according to the nature of the solvent and concentration. ExperimentsSulfobetaine-bearing polydisulfides were synthesized from dithiolane derivatives and then characterized. UCST behavior of the polymers in water and in mixtures containing different alcohols (methanol, ethanol, isopropanol) was investigated. The regeneration of monomers from the polymers in response to external stimuli was examined using UV–vis and circular dichroism (CD) spectroscopy. Tunable surface wettability were shown on the grafted polymers. FindingsDecreasing polarity and/or increasing alcohol percentage in the water mixtures induced an increase in the cloud points of the polymers in the solutions. Thermoresponsive behaviour were repeatable and fully reversible with negligible hysteresis from aggregate to unimer state. The regeneration of monomers by depolymerization was tunable by temperature and sunlight. A thickness dependence on surface wettability was observed on wafers covalently modified with polydisulfides. This is the first report of sulfobetaine-based polydisulfides showing tunable UCST behavior and surface wettability.

Bioinspired Thermoresponsive Xyloglucan–Cellulose Nanocrystal Hydrogels

Thermoresponsive hydrogels present unique properties, such as tunable mechanical performance or changes in volume, which make them attractive for applications including wound healing dressings, drug delivery vehicles, and implants, among others. This work reports the implementation of bioinspired thermoresponsive hydrogels composed of xyloglucan (XG) and cellulose nanocrystals (CNCs). Starting from tamarind seed XG (XGt), thermoresponsive XG was obtained by enzymatic degalactosylation (DG-XG), which reduced the galactose residue content by ∼50% and imparted a reversible thermal transition. XG with native composition and comparable molar mass to DG-XG was produced by an ultrasonication treatment (XGu) for a direct comparison of behavior. The hydrogels were prepared by simple mixing of DG-XG or XGu with CNCs in water. Phase diagrams were established to identify the ratios of DG-XG or XGu to CNCs that yielded a viscous liquid, a phase-separated mixture, a simple gel, or a thermoresponsive gel. Gelation occurred at a DG-XG or XGu to CNC ratio higher than that needed for the full surface coverage of CNCs and required relatively high overall concentrations of both components (tested concentrations up to 20 g/L XG and 30 g/L CNCs). This is likely a result of the increase in effective hydrodynamic volume of CNCs due to the formation of XG-CNC complexes. Investigation of the adsorption behavior indicated that DG-XG formed a more rigid layer on CNCs compared to XGu. Rheological properties of the hydrogels were characterized, and a reversible thermal transition was found for DG-XG/CNC gels at 35 °C. This thermoresponsive behavior provides opportunities to apply this system widely, especially in the biomedical field, where the mechanical properties could be further tuned by adjusting the CNC content.

LCST and UCST Transition of Poly(DMAEMA‐b‐MEO2MA) Copolymer in KHP Buffer

AbstractBlock copolymers of poly(2‐(dimethylamino)ethyl methacrylate) and poly(di(ethylene glycol) methyl ether methacrylate) (poly(DMAEMA‐b‐MEO2MA)) are successfully prepared by sequential reversible addition‐fragmentation chain transfer polymerization and evaluated its thermoresponsive behavior in acidic potassium hydrogen phthalate buffer. Individual block of the corresponding block copolymers exhibits lower critical solution temperature (LCST) transition whereas the synthesized block copolymers are found to exhibit dual thermoresponsive behavior: LCST at low temperatures due to the MEO2MA block and upper critical solution temperature (UCST) at high temperatures due to phthalate crosslinked protonated PDMAEMA block. The agglomeration at LCST is effectively enhanced by the ion–ion interactions within the chains. However, at higher temperature the hydrophobicity by the low hydration due to inter‐ionic interactions is disrupted at UCST, resulting in a transparent solution. The temperature‐dependent phase transition of the copolymer (i.e., from micelles to agglomerates, and reversibly to micelles) is confirmed using dynamic light scattering, UV–visible spectroscopy, and transmission electron microscopy. The unique dual thermoresponsive behavior upon heating and cooling cycles is found to exhibit very small hysteresis. The morphological transformation during LSCT and UCST‐type phase transition is explained via a proposed schematic illustration.

Cooling-Triggered Release from Mesoporous Poly(N-isopropylacrylamide) Microgels at Physiological Conditions.

Poly(N-isopropylacrylamide) (pNIPAM) hydrogels have broad potential applications as drug delivery vehicles because of their thermoresponsive behavior. pNIPAM loading/release performances are directly affected by the gel network structure. Therefore, there is a need with the approaches for accurate design of 3D pNIPAM assemblies with the structure ordered at the nanoscale. This study demonstrates size-selective spontaneous loading of macromolecules (dextrans 10−500 kDa) into pNIPAM microgels by microgel heating from 22 to 35 °C (microgels collapse and trap dextrans) followed by the dextran release upon further cooling down to 22 °C (microgels swell back) . This temperature-mediated behavior is fully reversible. The structure of pNIPAM microgels was tailored via hard templating and cross-linking of the hydrogel using sacrificial mesoporous cores of vaterite CaCO3 microcrystals. In addition, the fabrication of hollow thermoresponsive pNIPAM microshells has been demonstrated, utilizing vaterite microcrystals that had narrower pores. The proposed approach for heating-triggered encapsulation and cooling-triggered release into/from pNIPAM microgels may pave the ways for applications of pNIPAM hydrogels for skin and transdermal cooling-responsive drug delivery in the future.

Thermo-Responsive Methylcellulose Hydrogels: From Design to Applications as Smart Biomaterials.

Methylcellulose (MC) is an attractive material used to produce thermo-responsive hydrogels. They undergo sol-gel transition when a critical temperature is reached, thus modifying their properties (e.g., physicochemical and mechanical) in response to temperature changes. This behavior is particularly attractive when the body temperature acts as a trigger to modulate the thermo-responsive behavior of MC hydrogels. In this regard, exciting advances have been achieved in the field of cell and drug delivery, tissue engineering, and regenerative medicine, making MC a very attractive and versatile biomaterial. This review aims to present MC hydrogels, examining their preparation, physical properties, and tunability of thermal response, lastly moving to a comprehensive depiction of both their conventional and innovative applications for tissue regeneration purposes. In particular, three main families of applications are introduced: (1) in situ gelling systems, which undergo sol-gel transition upon delivery into a target site (e.g., tissue or organ), assisting the regeneration of the latter both in the presence or absence of loading components (e.g., cells, biomolecules, and inorganic materials); (2) three-dimensional (3D) (bio)printing, where the sol-gel transition is induced by heating MC-based (bio)inks after printing, obtaining 3D tissue-engineered substitutes with defined geometries and high shape fidelity; (3) smart culture surfaces, where the hydrophilic/hydrophobic transition of MC is exploited to reach a selective attachment/detachment of cells, offering the possibility to obtain cell sheets and cell bodies for tissue reconstruction without the need of any proteolytic enzyme. The main limitations of MC hydrogels will be then examined, together with current solutions to overcome them. Moreover, an overview of the future directions in the field of MC smart hydrogels will be given, with particular focus on the design of multiresponsive systems capable to respond to multiple stimuli (e.g., chemical and biological stimuli), toward the development of more patient-specific treatments. Finally, an overview of the patents and clinical trials describing the use of MC will be given, retracing the abovementioned families of application.

Multiarm Star-Crosslinked Hydrogel: Polymer Network with Thermoresponsive Free-End Chains Densely Connected to Crosslinking Points.

Soft tissue in biological system is a hydrogel with elaborate structure exhibiting repeatable dynamic function. In order to approach such sophisticated system, precise construction of a designed network with multi-components is desired. This communication presents a novel hydrogel having highly dense stimuli-responsive free-end chains around crosslinking structure. A key molecule is a core-crosslinked star-shaped polymer with multiple thermoresponsive arms, which can be prepared by reversible addition-fragmentation chain transfer polymerization of divinyl crosslinker with poly(N-isopropylacrylamide) (PNIPAAm) macro-chain transfer agent and have a number of unreacted carbon-carbon double bonds in the core. These unreacted double bonds can be utilized as a crosslinker for poly(acrylamide) (PAAm) gel synthesis by free radical polymerization. The obtained gel contains homogeneously dispersed star PNIPAAms as crosslinking points and exhibits thermoresponsive swelling behavior in water depending on the star contents. In particular, the gel with low content of the star crosslinker shows localized responsive behavior with expansion and shrinkage of the star in one molecule. The mechanical properties of the star-crosslinked gel are significantly high compared to the conventional PAAm gels particularly in compressive strength (≈9MPa). Moreover, the star-crosslinked gel has thermoresponsive mechanical toughening property.

Tuning of Morphology by Chirality in Self-Assembled Structures of Bis(Urea) Amphiphiles in Water.

We present the synthesis and self‐assembly of a chiral bis(urea) amphiphile and show that chirality offers a remarkable level of control towards different morphologies. Upon self‐assembly in water, the molecular‐scale chiral information is translated to the mesoscopic level. Both enantiomers of the amphiphile self‐assemble into chiral twisted ribbons with opposite handedness, as supported by Cryo‐TEM and circular dichroism (CD) measurements. The system presents thermo‐responsive aggregation behavior and combined transmittance measurements, temperature‐dependent UV, CD, TEM, and micro‐differential scanning calorimetry (DSC) show that a ribbon‐to‐vesicles transition occurs upon heating. Remarkably, chirality allows easy control of morphology as the self‐assembly into distinct aggregates can be tuned by varying the enantiomeric excess of the amphiphile, giving access to flat sheets, helical ribbons, and twisted ribbons.

Highly stable and thermo-responsive gel foams by synergistically combining glycyrrhizic acid nanofibrils and cellulose nanocrystals

HypothesisNatural saponin glycyrrhizic acid (GA) and GA nanofibrils (GNFs) are effective foaming agents for formulation of aqueous food-grade foams. Through the synergistic combination of soft semiflexible GNFs with rigid nanofiller cellulose nanocrystals (CNCs), it should be possible to create advanced composite foams with a more complex structure and diverse properties including high stability and stimuli responsiveness. ExperimentsFoams containing mixtures of GNFs and CNCs were prepared, and their formation and stability were investigated. A range of microscopy techniques and small deformation oscillatory shear were adopted to examine the microstructure and viscoelasticity of foams, and a stabilization mechanism for highly stable foams was then established. Further, the temperature-responsive destabilization of foams was evaluated. FindingsCNCs are homogeneously distributed in the architecture and mechanically reinforce the GNF fibrillar network, leading to a highly viscoelastic composite network in the continuous phase of foams, which is the key factor responsible for their high stability. Such ultra-stable gel foams display tunable thermo-responsive behavior and a rapid on-demand destabilization upon heating by inducing a phase transition of the bulk composite network. Our work opens up new scenarios on the use of a novel combination of all-natural, sustainable nanoscale building blocks to develop aqueous “superfoams” which are highly stable, stimulable and processable.

Thermoresponsive Poly(vinyl methyl ether) (PVME) Retained by 3-Aminopropyltriethoxysilane (APTES) Network

Thermoresponsive polymers (TRP)s have been widely used for various applications from controlling membrane fouling in separation to cell/cell sheet harvesting in regenerative medicine. While poly(N-isopropylacrylamide) (pNIPAAm) is the most commonly used TRP, less expensive and easily processed poly(vinyl methyl ether) (PVME) also shows a hydrophilic to hydrophobic transition at 32-35 °C, near physiological conditions. In this study, we investigated the processing conditions for retaining a stable layer of PVME thin film on silica surfaces via entrapment in a 3-aminopropyltriethoxysilane (APTES) network. In addition, the thermoresponsive behaviors (TRB) of the retained PVME films were evaluated. Blend thin films of PVME/APTES with 90:10 and 50:50 mass ratios were spin-coated from their solutions in ethanol under ambient conditions and then annealed in a vacuum oven at 40, 60, 80, or 120 °C for 1, 2, or 3 days. The annealed films were then thoroughly rinsed with room temperature water and then soaked in water for 3 days. Our results showed that annealing at a temperature of ≥40 °C was necessary for retaining a PVME film on the surface. The higher annealing temperature led to greater film retention, probably due to the formation of a tighter APTES network. Regardless of processing conditions, all retained PVME films showed TRB, determined by water contact angles below and above the transition temperature of PVME. Additionally, particle attachment and protein adsorption on retained PVME films showed lower attachment or adsorption at room temperature as compared to that at 37 °C, and a greater difference was observed for the 90:10 blend where more PVME was consisted. Furthermore, human mesenchymal stem cells attached and proliferated on the retained PVME surfaces at 37 °C and rapidly detached at room temperature. These results illustrated the potential applications of PVME surfaces as thermoresponsive supports for low-fouling applications and noninvasive cell harvesting.

Catalytic behavior of a thermo-responsive PVDF/microgel@Pd membrane for 2- nitroaniline degradation

Catalytic degradation of 2- nitroaniline is carried out under a penetrative flow and circular cross flow model as well as in the static state by a novel thermo-responsive catalytic membrane prepared by inserting Pd nanoparticles decorated thermo-responsive microgels into PVDF membrane pores. Due to the special thermo-responsive behavior of the catalytic membrane, increasing the temperature of the penetrative flow degradation from 30 to 35℃ can make the flux increase by at least 30 % and simultaneously the conversion increase by at least 0.3 %, significantly enhancing the reaction efficiency and the product discharge. In addition, the circular cross flow degradation shows a much higher rate than the static degradation. In brief, this membrane can well execute the catalytic degradation with side reactions and timely remove the products by the penetrative flow. Further more, the catalytic membrane can also well execute the catalytic degradation without side reactions by the circular cross flow.

Influence of Buffers, Ionic Strength, and pH on the Volume Phase Transition Behavior of Acrylamide-Based Nanogels.

The use of covalently crosslinked nanogels for applications in biology and medicine is dependent on their properties and characteristics, which often change because of the biological media involved. Understanding the role of salts, ionic strength and pH in altering specific properties is key to progress in this area. We studied the effect of both chemical structure and media environment on the thermoresponsive behavior of nanogels. A small library of methylenebisacrylamide (MBA) crosslinked nanogels were prepared using N-isopropylacrylamide (NIPAM) or N-n-propylacrylamide (NPAM), in combination with functional monomers N-hydroxyethylacrylamide (HEAM) and N-acryloyl-l-proline (APrOH). The thermoresponsive properties of nanogels were evaluated in phosphate buffer, tris-acetate buffer and Ringer HEPES, with varying concentrations and ionic strengths. The presence of ions facilitates the phase separation of nanogels, and this “salting-out” effect strongly depends on the electrolyte concentration as well as the specificity of individual anions, e.g., their positions in the Hofmeister series. A subtle change in the chemical structure of the side chain of the monomer from NIPAM to NPAM leads to a reduction of the volume phase transition temperature (VPTT) value by ~10 °C. The addition of hydrophilic comonomers such as HEAM, on the other hand, causes a ~20 °C shift in VPTT to higher values. The data highlight the significant role played by the chemical structure of the monomers used, with hydrophobicity and rigidity closely interlinked in determining thermoresponsive behavior. Furthermore, the volume phase transition temperature (VPTT) of nanogels copolymerized with ionizable APrOH comonomer can be tailored by changes in the pH of buffer solutions. This temperature-controlled phase transition is driven by intricate interplay involving the entropy of mixing, electrostatic interactions, conformational transitions, and structural rigidity. These results highlight the importance of understanding the physiochemical properties and behavior of covalently crosslinked nanogels in a biological environment prior to their applications in life-science, such as temperature/pH-triggered drug delivery systems.

Thermoresponsive Starch for the Flocculation of Oil Sands Mature Fine Tailings.

The reclamation of land and recovery of water from tailing ponds created during bitumen extraction from oil sands is a major technical and environmental challenge. In the current study, thermoresponsive hydroxybutylated (HB) corn starch (HB-CS) and potato starch (HB-PS), with lower critical solution temperatures (LCSTs) ranging from 36 to 45 °C, were examined as flocculants for oil sands mature fine tailings (MFT). The ability of different doses of the HB-CS and HB-PS to flocculate 2 and 10 wt % MFT, prepared by diluting 35 wt % MFT in tap water, in terms of the initial settling rate (ISR), supernatant turbidity (ST), sediment solids content (SSC), and water recovery (WR), was examined at temperatures below and above their LCSTs. The thermoresponsive HB-CS and HB-PS were good flocculants of MFT, and their thermoresponsive behavior was essential for optimal results in that they were considerably more effective in several aspects at temperatures above their LCSTs than below. In terms of ISRs, the HB-PS was a considerably better flocculant than the HB-CS, and this was especially so with the 10 wt % MFT. With the HB-PS, the ISR was lower when using diluted MFT prepared with tap water as opposed to simulated oil sands process water.

Entropy Rules: Molecular Dynamics Simulations of Model Oligomers for Thermoresponsive Polymers.

We attempted to attain atomic-scale insights into the mechanism of the heat-induced phase transition of two thermoresponsive polymers containing amide groups, poly(N-isopropylacrylamide) (PNIPAM) and poly(2-isopropyl-2-oxazoline) (PIPOZ), and we succeeded in reproducing the existence of lower critical solution temperature (LCST). The simulation data are in accord with experimental findings. We found out that the entropy has an important contribution to the thermodynamics of the phase separation transition. Moreover, after decomposing further the entropy change to contributions from the solutes and from the solvent, it appeared out that the entropy of the solvent has the decisive share for the lowering of the free energy of the system when increasing the temperature above the LCST. Our conclusion is that the thermoresponsive behavior is driven by the entropy of the solvent. The water molecules structured around the functional groups of the polymer that are exposed to contact with the solvent in the extended conformation lower the enthalpy of the system, but at certain temperature the extended conformation of the polymer collapses as a result of dominating entropy gain from “released” water molecules. We stress also on the importance of using more than one reference molecule in the simulation box at the setup of the simulation.

Controlling the Chain Folding for the Synthesis of Single-Chain Polymer Nanoparticles Using Thermoresponsive Polymers

Synthetic polymer single-chain nanoparticles (SCNPs) are an emerging new class of nanomaterials that possess similar folded structures as natural proteins. However, most SCNPs reported so far are p...

Enrichment of Charged Monomers Explains Non-monotonic Polymer Volume Fraction Profiles of Multi-stimulus Responsive Copolymer Brushes.

Multi-stimulus responsive poly(2-(2-methoxyethoxy)ethyl methacrylate-co-2-(diethylamino)ethyl methacrylate) [P(MEO2MA-co-DEA)] 80:20 mol % copolymer brushes were synthesized on planar silica substrates via surface-initiated activators continuously regenerated via electron transfer atom transfer radical polymerization. Brush thickness was sensitive to changes in pH and temperature as monitored with ellipsometry. At low pH, the brush is charged and swollen, while at high pH, the brush is uncharged and more collapsed. Clear thermoresponsive behavior is also observed with the brush more swollen at low temperatures compared to high temperatures at both high and low pH. Neutron reflectometry was used to determine the polymer volume fraction profiles (VFPs) at various pH values and temperatures. A region of lower polymer content, or a depletion region, near the substrate is present in all of the experimental polymer VFPs, and it is more pronounced at low pH (high charge) and less so at high pH (low charge). Polymer VFPs calculated through numerical self-consistent field theory suggest that enrichment of DEA monomers near the substrate results in the experimentally observed non-monotonic VFPs. Adsorption of DEA monomers to the substrate prior to initiation of polymerization could give rise to DEA segment-enriched region proximal to the substrate.

A difunctional Pluronic®127-based in situ formed injectable thermogels as prolonged and controlled curcumin depot, fabrication, in vitro characterization and in vivo safety evaluation

Curcumin has been reported to be used widely against many types of pathological conditions in clinics. However, due to its limitations such as poor solubility, poor oral absorption and low stability have limited its applications. In the current study, a series of novel chemically cross-linkable depot gel formulations were developed based on thermoresponsive micellar polymer (Pluronic®127) with polyelectrolyte hydrophilic monomer, that is, 2-acrylamido-2-methylpropane sulfonic acid by cold and in situ grafting polymerization method. The formulations were aimed to deliver curcumin at controlled rate from in situ formed depot after administration through subcutaneous route in vivo. The sol-gel phase transitions of formulations were observed by rheological analysis, tube titling and optical transmittance measurements. Maximum swelling of gel formulations was observed at pH 7.4 and below CGT, that is, 25 °C. The in vitro release profile exhibits maximum drug release at pH 7.4 and 25 °C owing to relaxed gel state. In vitro degradation profile of gel formulations showed controlled degradation rate. Cell growth inhibition study confirmed the biocompatibility and safe nature of bare gel formulations against L929 cell lines. In vitro cytotoxic study showed that curcumin loaded in gel formulation has controlled pharmacological activity against HeLa and MCF-7 cancer cells as compared to free drug solution. The IC50 values calculated for pure curcumin solution (30 ± 0.77 µg/ml for HeLa and 27 ± 0.39 µg/ml for MCF-7) were found higher in comparison to curcumin-loaded thermogels against HeLa (19 ± 0.28 µg/ml and 23 ± 0.81 µg/ml) and MCF-7 (22 ± 0.54 µg/ml and 21 ± 0.49 µg/ml). Histopathological and hematological analysis showed the biocompatible nature of hydrogels. Structural confirmation was done by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance spectroscopy (1H NMR). Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) confirmed the thermal stability of the gel formulation. The porous structure of gel formulations was assessed by scanning electron microscopic (SEM) analysis. Results concluded that newly developed gel formulations have thermoresponsive behavior with phase transition at body temperature and can be used as in situ controlled drug depot.

The influence of arm composition on the self-assembly of low-functionality telechelic star polymers in dilute solutions

We combine synthesis, physical experiments, and computer simulations to investigate self-assembly patterns of low-functionality telechelic star polymers (TSPs) in dilute solutions. In particular, in this work, we focus on the effect of the arm composition and length on the static and dynamic properties of TSPs, whose terminal blocks are subject to worsening solvent quality upon reducing the temperature. We find two populations, single stars and clusters, that emerge upon worsening the solvent quality of the outer block. For both types of populations, their spatial extent decreases with temperature, with the specific details (such as temperature at which the minimal size is reached) depending on the coupling between inter- and intra-molecular associations as well as their strength. The experimental results are in very good qualitative agreement with coarse-grained simulations, which offer insights into the mechanism of thermoresponsive behavior of this class of materials.

Biodegradable thermoresponsive polymers: Applications in drug delivery and tissue engineering

Thermoresponsive polymers have been investigated for a variety of clinical applications which make use of in situ gelation at physiological temperatures. However, for biomedical applications such as drug delivery and tissue engineering, thermoresponsive behavior and tunability must be balanced with biocompatibility and degradation kinetics. Significant research regarding polymer blends and copolymers has been conducted to modulate key characteristics of thermoresponsive polymers, including degradation kinetics and mechanical properties. Additionally, cell sheets, injectable materials, 3D-printed scaffolds, and nanomaterials have been fabricated which harness the thermoresponsive features of such polymers for enhanced control of bioactive molecule delivery and tissue regeneration. This perspective thus highlights important considerations for thermoresponsive hydrogels in tissue engineering and drug delivery, discusses several commonly explored natural and synthetic thermoresponsive polymers, and provides examples of advanced processing and fabrication techniques using thermoresponsive polymers for biomedical applications.

Synthesis of poly(Asparagine-co-phenylalanine) copolymers, analogy with thermosensitive poly(acrylamide-co-styrene) copolymers and formation of PEGylated nanoparticles

We presented optimized synthetic pathways to high purity L-phenylalanine (Phe) and L-asparagine (Asn) derived N-carboxyanhydrides (NCA) in one-pot processes and in a highly reproducible manner. Ring-opening homopolymerizations of Asn-NCA and Phe-NCA were successfully achieved together with their copolymerization in an attempt to mimic upper critical solution temperature (UCST) vinylic poly(acrylamide-co-styrene) (P(Aam-co-St)) copolymers. Poly(asparagine-co-phenylalanine) (P(Asn-co-Phe)) copolypeptides of different Asn-to-Phe ratio were prepared and their thermoresponsive behavior was investigated in aqueous solution. Unfortunately, polymer aggregation imparted by strong hydrophobic interactions favored due to presence of β-sheet structures prevented achieving thermosensitive response in aqueous media in the 50–62 °C range conversely to its vinylic counterpart. However, by taking advantage of those strong hydrophobic interactions, PEG-b-PAsn and PEG-b-PPhe diblock copolymers were prepared from amino-PEG initiators and PEG-b-PAsn was successfully formulated into PEGylated nanoparticles of ~270 nm.