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12 pages, 3997 KiB

Open AccessArticle

NIPAm-Based Modification of Poly(L-lysine): A pH-Dependent LCST-Type Thermo-Responsive Biodegradable Polymer

by Aggeliki Stamou, Hermis Iatrou and Constantinos Tsitsilianis

Polymers 2022, 14(4), 802; https://doi.org/10.3390/polym14040802 - 18 Feb 2022

Cited by 10 | Viewed by 2727

Polylysine is a biocompatible, biodegradable, water soluble polypeptide. Thanks to the pendant primary amines it bears, it is susceptible to modification reactions. In this work Poly(L-lysine) (PLL) was partially modified via the effortless free-catalysed aza-Michael addition reaction at room temperature by grafting N-isopropylacrylamide [...] Read more.

Polylysine is a biocompatible, biodegradable, water soluble polypeptide. Thanks to the pendant primary amines it bears, it is susceptible to modification reactions. In this work Poly(L-lysine) (PLL) was partially modified via the effortless free-catalysed aza-Michael addition reaction at room temperature by grafting N-isopropylacrylamide (NIPAm) moieties onto the amines. The resulting PLL-g-NIPAm exhibited LCST-type thermosensitivity. The LCST can be tuned by the NIPAm content incorporated in the macromolecules. Importantly, depending on the NIPAm content, LCST is highly dependent on pH and ionic strength due to ionization capability of the remaining free lysine residues. PLL-g-NIPAm constitutes a novel biodegradable LCST polymer that could be used as “smart” block in block copolymers and/or terpolymers, of any macromolecular architecture, to design pH/Temperature-responsive self-assemblies (nanocarriers and/or networks) for potential bio-applications. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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16 pages, 3289 KiB

Open AccessArticle

Inhomogeneities in PNIPAM Aqueous Solutions: The Inside View by Spin Probe EPR Spectroscopy

by Ekaterina M. Zubanova, Sergei V. Kostjuk, Peter S. Timashev, Yury A. Rochev, Alexander I. Kokorin, Mikhail Ya. Melnikov and Elena N. Golubeva

Polymers 2021, 13(21), 3829; https://doi.org/10.3390/polym13213829 - 05 Nov 2021

Cited by 3 | Viewed by 2418

Abstract

Coil to globule transition in poly(N-isopropylacrylamide) aqueous solutions was studied using spin probe continuous-wave electronic paramagnetic resonance (CW EPR) spectroscopy with an amphiphilic TEMPO radical as a guest molecule. Using Cu(II) ions as the “quencher” for fast-moving radicals in the liquid phase allowed [...] Read more.

Coil to globule transition in poly(N-isopropylacrylamide) aqueous solutions was studied using spin probe continuous-wave electronic paramagnetic resonance (CW EPR) spectroscopy with an amphiphilic TEMPO radical as a guest molecule. Using Cu(II) ions as the “quencher” for fast-moving radicals in the liquid phase allowed obtaining the individual spectra of TEMPO radicals in polymer globule and observing inhomogeneities in solutions before globule collapsing. EPR spectra simulations confirm the formation of molten globules at the first step with further collapsing and water molecules coming out of the globule, making it denser. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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10 pages, 1085 KiB

Open AccessArticle

Thermocontrolled Reversible Enzyme Complexation-Inactivation-Protection by Poly(N-acryloyl glycinamide)

by Pavel I. Semenyuk, Lidia P. Kurochkina, Lauri Mäkinen, Vladimir I. Muronetz and Sami Hietala

Polymers 2021, 13(20), 3601; https://doi.org/10.3390/polym13203601 - 19 Oct 2021

Cited by 5 | Viewed by 2025

Abstract

A prospective technology for reversible enzyme complexation accompanied with its inactivation and protection followed by reactivation after a fast thermocontrolled release has been demonstrated. A thermoresponsive polymer with upper critical solution temperature, poly(N-acryloyl glycinamide) (PNAGA), which is soluble in water at [...] Read more.

A prospective technology for reversible enzyme complexation accompanied with its inactivation and protection followed by reactivation after a fast thermocontrolled release has been demonstrated. A thermoresponsive polymer with upper critical solution temperature, poly(N-acryloyl glycinamide) (PNAGA), which is soluble in water at elevated temperatures but phase separates at low temperatures, has been shown to bind lysozyme, chosen as a model enzyme, at a low temperature (10 °C and lower) but not at room temperature (around 25 °C). The cooling of the mixture of PNAGA and lysozyme solutions from room temperature resulted in the capturing of the protein and the formation of stable complexes; heating it back up was accompanied by dissolving the complexes and the release of the bound lysozyme. Captured by the polymer, lysozyme was inactive, but a temperature-mediated release from the complexes was accompanied by its reactivation. Complexation also partially protected lysozyme from proteolytic degradation by proteinase K, which is useful for biotechnological applications. The obtained results are relevant for important medicinal tasks associated with drug delivery such as the delivery and controlled release of enzyme-based drugs. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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15 pages, 3232 KiB

Open AccessArticle

Temperature/Reduction Dual Response Nanogel Is Formed by In Situ Stereocomplexation of Poly (Lactic Acid)

by Wenli Gao, Zhidan Wang, Fei Song, Yu Fu, Qingrong Wu and Shouxin Liu

Polymers 2021, 13(20), 3492; https://doi.org/10.3390/polym13203492 - 12 Oct 2021

Cited by 2 | Viewed by 1650

Abstract

A novel type of dual responsive nanogels was synthesized by physical crosslinking of polylactic acid stereocomplexation: temperature and reduction dual stimulation responsive gels were formed in situ by mixing equal amounts of PLA (Poly (Lactic Acid)) enantiomeric graft copolymer micellar solution; the properties [...] Read more.

A novel type of dual responsive nanogels was synthesized by physical crosslinking of polylactic acid stereocomplexation: temperature and reduction dual stimulation responsive gels were formed in situ by mixing equal amounts of PLA (Poly (Lactic Acid)) enantiomeric graft copolymer micellar solution; the properties of double stimulation response make it more targeted in the field of drug release. The structural composition of the gels was studied by proton nuclear magnetic resonance (¹H NMR) and Fourier transform infrared spectroscopy (FT-IR). Using transmission electron microscope (TEM) and dynamic light scattering (DLS) instruments, the differences in morphology and particle size were analyzed (indicating that nanogels have dual stimulus responses of temperature sensitivity and reduction). The Wide-Angle X-ray diffractionr (WAXD) was used to prove the stereocomplexation of PLA in the gels, the mechanical properties and gelation process of the gels were studied by rheology test. The physically cross-linked gel network generated by the self-recombination of micelles and then stereo-complexation has a more stable structure. The results show that the micelle properties, swelling properties and rheological properties of nanogels can be changed by adjusting the degree of polymerization of polylactic acid. In addition, it provides a safe and practical new method for preparing stable temperature/reduction response physical cross-linked gel. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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12 pages, 1718 KiB

Open AccessArticle

Modulating the Thermoresponse of Polymer-Protein Conjugates with Hydrogels for Controlled Release

by Vincent Huynh, Natalie Ifraimov and Ryan G. Wylie

Polymers 2021, 13(16), 2772; https://doi.org/10.3390/polym13162772 - 18 Aug 2021

Cited by 5 | Viewed by 2170

Abstract

Sustained release is being explored to increase plasma and tissue residence times of polymer-protein therapeutics for improved efficacy. Recently, poly(oligo(ethylene glycol) methyl ether methacrylate) (PEGMA) polymers have been established as potential PEG alternatives to further decrease immunogenicity and introduce responsive or sieving properties. [...] Read more.

Sustained release is being explored to increase plasma and tissue residence times of polymer-protein therapeutics for improved efficacy. Recently, poly(oligo(ethylene glycol) methyl ether methacrylate) (PEGMA) polymers have been established as potential PEG alternatives to further decrease immunogenicity and introduce responsive or sieving properties. We developed a drug delivery system that locally depresses the lower critical solution temperature (LCST) of PEGMA-protein conjugates within zwitterionic hydrogels for controlled release. Inside the hydrogel the conjugates partially aggregate through PEGMA-PEGMA chain interactions to limit their release rates, whereas conjugates outside of the hydrogel are completely solubilized. Release can therefore be tuned by altering hydrogel components and the PEGMA’s temperature sensitivity without the need for traditional controlled release mechanisms such as particle encapsulation or affinity interactions. Combining local LCST depression technology and degradable zwitterionic hydrogels, complete release of the conjugate was achieved over 13 days. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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15 pages, 13702 KiB

Open AccessArticle

Characterization of Thermoresponsive Poly-N-Vinylcaprolactam Polymers for Biological Applications

by Lorenzo Marsili, Michele Dal Bo, Giorgio Eisele, Ivan Donati, Federico Berti and Giuseppe Toffoli

Polymers 2021, 13(16), 2639; https://doi.org/10.3390/polym13162639 - 08 Aug 2021

Cited by 19 | Viewed by 4515

Abstract

Poly-N-Vinylcaprolactam (PNVCL) is a thermoresponsive polymer that exhibits lower critical solution temperature (LCST) between 25 and 50 °C. Due to its alleged biocompatibility, this polymer is becoming popular for biomedical and environmental applications. PNVCL with carboxyl terminations has been widely used for the [...] Read more.

Poly-N-Vinylcaprolactam (PNVCL) is a thermoresponsive polymer that exhibits lower critical solution temperature (LCST) between 25 and 50 °C. Due to its alleged biocompatibility, this polymer is becoming popular for biomedical and environmental applications. PNVCL with carboxyl terminations has been widely used for the preparation of thermoresponsive copolymers, micro- and nanogels for drug delivery and oncological therapies. However, the fabrication of such specific targeting devices needs standardized and reproducible preparation methods. This requires a deep understanding of how the miscibility behavior of the polymer is affected by its structural properties and the solution environment. In this work, PNVCL-COOH polymers were prepared via free radical polymerization (FRP) in order to exhibit LCST between 33 and 42 °C. The structural properties were investigated with NMR, FT-IR and conductimetric titration and the LCST was calculated via UV-VIS and DLS. The LCST is influenced by the molecular mass, as shown by both DLS and viscosimetric values. Finally, the behavior of the polymer was described as function of its concentration and in presence of different biologically relevant environments, such as aqueous buffers, NaCl solutions and human plasma. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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21 pages, 3436 KiB

Open AccessArticle

Features of Solution Behavior of Polymer Stars with Arms of Poly-2-alkyl-2-oxazolines Copolymers Grafted to the Upper Rim of Calix[8]arene

by Tatyana Kirila, Alina Amirova, Alexey Blokhin, Andrey Tenkovtsev and Alexander Filippov

Polymers 2021, 13(15), 2507; https://doi.org/10.3390/polym13152507 - 29 Jul 2021

Cited by 6 | Viewed by 1552

Abstract

Star-shaped polymers with arms of block and gradient copolymers of 2-ethyl- and 2-isopropyl-2-oxazolines grafted to the upper rim of calix[8]arene were synthesized by the “grafting from” method. The ratio of 2-ethyl- and 2-isopropyl-2-oxazoline units was 1:1. Molar masses and hydrodynamic characteristics were measured [...] Read more.

Star-shaped polymers with arms of block and gradient copolymers of 2-ethyl- and 2-isopropyl-2-oxazolines grafted to the upper rim of calix[8]arene were synthesized by the “grafting from” method. The ratio of 2-ethyl- and 2-isopropyl-2-oxazoline units was 1:1. Molar masses and hydrodynamic characteristics were measured using molecular hydrodynamics and optics methods in 2-nitropropane. The arms of the synthesized stars were short and the star-shaped macromolecules were characterized by compact dimensions and heightened intramolecular density. The influence of the arm structure on the conformation of star molecules was not observed. At low temperatures, the aqueous solutions of the studied stars were not molecular dispersed but individual molecules prevailed. One phase transition was detected for all solutions. The phase separation temperatures decreased with a growth of the content of more hydrophobic 2-isopropyl-2-oxazoline units. It was shown that the way of arms grafting to the calix[8]arene core affects the behavior of aqueous solutions of star-shaped poly-2-alkyl-2-oxazoline copolymers. In the case of upper rim functionalization, the shape of calix[8]arene resembles a plate. Accordingly, the core is less shielded from the solvent and the phase separation temperatures are lower than those for star-shaped poly-2-alkyl-2-oxazolines with lower rim functionalization of the calix[8]arene. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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16 pages, 1956 KiB

Open AccessArticle

Controlling Growth of Poly (Triethylene Glycol Acrylate-Co-Spiropyran Acrylate) Copolymer Liquid Films on a Hydrophilic Surface by Light and Temperature

by Aziz Ben-Miled, Afshin Nabiyan, Katrin Wondraczek, Felix H. Schacher and Lothar Wondraczek

Polymers 2021, 13(10), 1633; https://doi.org/10.3390/polym13101633 - 18 May 2021

Cited by 4 | Viewed by 3101

Abstract

A quartz crystal microbalance with dissipation monitoring (QCM-D) was employed for in situ investigations of the effect of temperature and light on the conformational changes of a poly (triethylene glycol acrylate-co-spiropyran acrylate) (P (TEGA-co-SPA)) copolymer containing 12–14% of spiropyran [...] Read more.

A quartz crystal microbalance with dissipation monitoring (QCM-D) was employed for in situ investigations of the effect of temperature and light on the conformational changes of a poly (triethylene glycol acrylate-co-spiropyran acrylate) (P (TEGA-co-SPA)) copolymer containing 12–14% of spiropyran at the silica–water interface. By monitoring shifts in resonance frequency and in acoustic dissipation as a function of temperature and illumination conditions, we investigated the evolution of viscoelastic properties of the P (TEGA-co-SPA)-rich wetting layer growing on the sensor, from which we deduced the characteristic coil-to-globule transition temperature, corresponding to the lower critical solution temperature (LCST) of the PTEGA part. We show that the coil-to-globule transition of the adsorbed copolymer being exposed to visible or UV light shifts to lower LCST as compared to the bulk solution: the transition temperature determined acoustically on the surface is 4 to 8 K lower than the cloud point temperature reported by UV/VIS spectroscopy in aqueous solution. We attribute our findings to non-equilibrium effects caused by confinement of the copolymer chains on the surface. Thermal stimuli and light can be used to manipulate the film formation process and the film’s conformational state, which affects its subsequent response behavior. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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15 pages, 2990 KiB

Open AccessArticle

Self-Organization in Dilute Aqueous Solutions of Thermoresponsive Star-Shaped Six-Arm Poly-2-Alkyl-2-Oxazines and Poly-2-Alkyl-2-Oxazolines

by Tatyana Kirila, Anna Smirnova, Vladimir Aseyev, Andrey Tenkovtsev, Heikki Tenhu and Alexander Filippov

Polymers 2021, 13(9), 1429; https://doi.org/10.3390/polym13091429 - 29 Apr 2021

Cited by 4 | Viewed by 1685

Abstract

The behavior of star-shaped six-arm poly-2-alkyl-2-oxazines and poly-2-alkyl-2-oxazolines in aqueous solutions on heating was studied by light scattering, turbidimetry and microcalorimetry. The core of stars was hexaaza [2₆] orthoparacyclophane and the arms were poly-2-ethyl-2-oxazine, poly-2-isopropyl-2-oxazine, poly-2-ethyl-2-oxazoline, and poly-2-isopropyl-2-oxazoline. The arm structure [...] Read more.

The behavior of star-shaped six-arm poly-2-alkyl-2-oxazines and poly-2-alkyl-2-oxazolines in aqueous solutions on heating was studied by light scattering, turbidimetry and microcalorimetry. The core of stars was hexaaza [2₆] orthoparacyclophane and the arms were poly-2-ethyl-2-oxazine, poly-2-isopropyl-2-oxazine, poly-2-ethyl-2-oxazoline, and poly-2-isopropyl-2-oxazoline. The arm structure affects the properties of polymers already at low temperatures. Molecules and aggregates were present in solutions of poly-2-alkyl-2-oxazines, while aggregates of two types were observed in the case of poly-2-alkyl-2-oxazolines. On heating below the phase separation temperature, the characteristics of the investigated solutions did not depend practically on temperature. An increase in the dehydration degree of poly-2-alkyl-2-oxazines and poly-2-alkyl-2-oxazolines led to the formation of intermolecular hydrogen bonds, and aggregation was the dominant process near the phase separation temperature. It was shown that the characteristics of the phase transition in solutions of the studied polymer stars are determined primarily by the arm structure, while the influence of the molar mass is not so significant. In comparison with literature data, the role of the hydrophobic core structure in the formation of the properties of star-shaped polymers was analyzed. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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12 pages, 1767 KiB

Open AccessArticle

Influence of the Polymer Microstructure over the Phase Separation of Thermo-Responsive Nanoparticles

by Nicolò Manfredini, Marco Tomasoni, Mattia Sponchioni and Davide Moscatelli

Polymers 2021, 13(7), 1032; https://doi.org/10.3390/polym13071032 - 26 Mar 2021

Cited by 10 | Viewed by 2037

Abstract

Thermo-responsive nanoparticles (NPs), i.e., colloids with a sharp and often reversible phase separation in response to thermal stimuli, are coming to the forefront due to their dynamic behavior, useful in applications ranging from biomedicine to advanced separations and smart optics. What is guiding [...] Read more.

Thermo-responsive nanoparticles (NPs), i.e., colloids with a sharp and often reversible phase separation in response to thermal stimuli, are coming to the forefront due to their dynamic behavior, useful in applications ranging from biomedicine to advanced separations and smart optics. What is guiding the macroscopic behavior of these systems above their critical temperature is mainly the microstructure of the polymer chains of which these NPs are comprised. Therefore, a comprehensive understanding of the influence of the polymer properties over the thermal response is highly required to reproducibly target a specific behavior. In this study, we synthesized thermo-responsive NPs with different size, polymeric microstructure and hydrophilic-lipophilic balance (HLB) and investigated the role of these properties over their phase separation. We first synthesized four different thermo-responsive oligomers via Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization of poly(ethylene glycol)methyl ether methacrylate. Then, exploiting the RAFT living character, we chain-extended these oligomers with butyl methacrylate obtaining a library of NPs. Finally, we investigated the NP thermo-responsive behavior, their physical state above the cloud point (Tcp) as well as their reversibility once the stimulus is removed. We concluded that the solid content plays a minor role compared to the relative length of the two blocks forming the polymer chains. In particular, the longer the stabilizer, the more favored the formation of a gel. At the same time, the reversibility is mainly achieved at high HLB, independently from the absolute lengths of the block copolymers. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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18 pages, 3263 KiB

Open AccessArticle

Thermoresponsive Poly(N,N-diethylacrylamide-co-glycidyl methacrylate) Copolymers and Its Catalytically Active α-Chymotrypsin Bioconjugate with Enhanced Enzyme Stability

by György Kasza, Tímea Stumphauser, Márk Bisztrán, Györgyi Szarka, Imre Hegedüs, Endre Nagy and Béla Iván

Polymers 2021, 13(6), 987; https://doi.org/10.3390/polym13060987 - 23 Mar 2021

Cited by 8 | Viewed by 4800

Abstract

Responsive (smart, intelligent, adaptive) polymers have been widely explored for a variety of advanced applications in recent years. The thermoresponsive poly(N,N-diethylacrylamide) (PDEAAm), which has a better biocompatibility than the widely investigated poly(N,N-isopropylacrylamide), has gained increased [...] Read more.

Responsive (smart, intelligent, adaptive) polymers have been widely explored for a variety of advanced applications in recent years. The thermoresponsive poly(N,N-diethylacrylamide) (PDEAAm), which has a better biocompatibility than the widely investigated poly(N,N-isopropylacrylamide), has gained increased interest in recent years. In this paper, the successful synthesis, characterization, and bioconjugation of a novel thermoresponsive copolymer, poly(N,N-diethylacrylamide-co-glycidyl methacrylate) (P(DEAAm-co-GMA)), obtained by free radical copolymerization with various comonomer contents and monomer/initiator ratios are reported. It was found that all the investigated copolymers possess LCST-type thermoresponsive behavior with small extent of hysteresis, and the critical solution temperatures (CST), i.e., the cloud and clearing points, decrease linearly with increasing GMA content of these copolymers. The P(DEAAm-co-GMA) copolymer with pendant epoxy groups was found to conjugate efficiently with α-chymotrypsin in a direct, one-step reaction, leading to enzyme–polymer nanoparticle (EPNP) with average size of 56.9 nm. This EPNP also shows reversible thermoresponsive behavior with somewhat higher critical solution temperature than that of the unreacted P(DEAAm-co-GMA). Although the catalytic activity of the enzyme–polymer nanoconjugate is lower than that of the native enzyme, the results of the enzyme activity investigations prove that the pH and thermal stability of the enzyme is significantly enhanced by conjugation the with P(DEAAm-co-GMA) copolymer. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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Review

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20 pages, 9659 KiB

Open AccessReview

Recent Advances in Thermoresponsive OEGylated Poly(amino acid)s

by Chao Geng, Shixue Wang and Hongda Wang

Polymers 2021, 13(11), 1813; https://doi.org/10.3390/polym13111813 - 31 May 2021

Cited by 6 | Viewed by 2754

Abstract

Thermoresponsive polymers have been widely studied in the past decades due to their potential applications in biomedicine, nanotechnology, and so on. As is known, poly(N-isopropylacrylamide) (PNIPAM) and poly(oligo(ethylene glycol)methacrylates) (POEGMAs) are the most popular thermoresponsive polymers, and have been studied extensively. [...] Read more.

Thermoresponsive polymers have been widely studied in the past decades due to their potential applications in biomedicine, nanotechnology, and so on. As is known, poly(N-isopropylacrylamide) (PNIPAM) and poly(oligo(ethylene glycol)methacrylates) (POEGMAs) are the most popular thermoresponsive polymers, and have been studied extensively. However, more advanced thermoresponsive polymers with excellent biocompatibility, biodegradability, and bioactivity also need to be developed for biomedical applications. OEGylated poly(amino acid)s are a kind of novel polymer which are synthesized by attaching one or multiple oligo(ethylene glycol) (OEG) chains to poly(amino acid) (PAA).These polymers combine the great solubility of OEG, and the excellent biocompatibility, biodegradability and well defined secondary structures of PAA. These advantages allow them to have great application prospects in the field of biomedicine. Therefore, the study of OEGylated poly(amino acid)s has attracted more attention recently. In this review, we summarized the development of thermoresponsive OEGylated poly(amino acid)s in recent years, including the synthesis method (such as ring-opening polymerization, post-polymerization modification, and Ugi reaction), stimuli-response behavior study, and secondary structure study. We hope that this periodical summary will be more conducive to design, synthesis and application of OEGylated poly(amino acid)s in the future. Full article

(This article belongs to the Special Issue Advances in Thermoresponsive Polymers)

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