Thermosensitive Polymer Research Articles

Identification of constitutive law for 3d-printed bioresorbable thermosensitive polymer to design medical devices for soft tissue reconstruction

Identification of constitutive law for 3d-printed bioresorbable thermosensitive polymer to design medical devices for soft tissue reconstruction

Thermosensitive polymer assisted metal–organic framework for the determination of phenoxy carboxylic acid herbicides in environmental water samples

A simple and efficient method for the determination of five phenoxy carboxylic acid herbicides (PCAs) in environmental water samples was developed based on thermosensitive polymer assisted metal–organic framework as the adsorbent for micro-solid phase extraction. Under the optimized working conditions, the linearity was in the concentration ranges of 5–300 μg L−1 with a determination coefficient higher than 0.9980, respectively. The limits of detection and limits of quantification were in the range of 0.34–0.55 μg L−1 and 1.13–1.83 μg L−1, respectively. The intra-day and inter-day precision were in the range of 0.7–3.4 % and 2.6–3.5 %, respectively. The method was applied successfully to analyze PCAs in environmental water samples. The satisfactory relative recoveries (92.7 %–117.8 %) for the spiked samples in environmental water samples were achieved which demonstrated the proposed method has a potential application for the trace determination of PCAs from complex matrix. Besides, the developed method is proved to be simple, environmentally friendly and inexpensive.

A Temperature-Sensitive Fluorescent Supramolecular Polymer Constructed by Discrete Platinum(II) Metallacycle and Pillar[5]arene-Based Host-Guest Interactions.

The application of thermosensitive fluorescent supramolecular polymers in advanced optical materials, chemical sensors, artificial optical devices, and external stimulus responses remains underdeveloped. In this study, we introduced a novel method for constructing a mechanically interlocked fluorescent supramolecular polymer utilizing host-guest interactions, including C-H···π interactions and π-π stacking. This polymer exhibits outstanding temperature-sensitive fluorescence properties and is environmentally friendly due to its recyclability. Leveraging the polymer's fluorescence response at critical temperature ranges, we developed a high-temperature warning device. This device utilizes the temperature-sensitive fluorescence characteristic of the polymer to indicate dangerous temperature levels, thereby demonstrating its potential in practical safety applications.

Development of synergistic antifungal in situ gel of miconazole nitrate loaded microemulsion as a novel approach to treat vaginal candidiasis

Limited solubility is the main cause of the low local availability of anti-candidiasis drug, miconazole nitrate (MN). The study’s objective was to develop and characterize microemulsion (ME) based temperature-triggered in situ gel of MN for intravaginal administration to enhance local availability and antifungal activity. The solubility of MN was initially studied in different oils, surfactants, and co-surfactants. Then, pseudo-ternary phase diagrams were constructed to select the best ratio of various components. The ME formulations were characterized by thermodynamic study, droplet size, polydispersity index (PDI), viscosity, and in-vitro antifungal mean inhibition zone (MIZ). Selected MEs were incorporated into different in situ gel bases using a combination of two thermosensitive polymers (poloxamer (PLX) 407 and 188), with 0.6% of hydroxypropyl methylcellulose (HPMC K4M) and gellan gum (GG) as mucoadhesive polymer. ME-based gels (MG) were investigated for gelation temperature, gelation time, viscosity, spreadability, mucoadhesive strength, in vitro release profile, and MIZ test. Furthermore, the optimum MG was assessed for in vivo animal irritation test and FESEM investigation. Tea tree oil, lavender oil, tween 80, and propylene glycol (PG) were chosen for ME preparation for the optimal formulation; formulation ME7 and ME10 were chosen. After incorporation of the selected formulation into a mixture of P407 and P188 (18:2% w/w) with 0.6% mucoadhesive polymer, the resultant MG formulation (MG1) revealed optimum gelation temperature (33 ± 0.01℃) and appropriate viscosity with enhanced sustained release (98%) and retention through sheep vaginal mucosa, MG1 exhibited a better MIZ compared to the 2% MN gel formulation and the marketed MN product, and no rabbit vagina irritation. In conclusion, the miconazole nitrate-loaded MG-based formula sustained the duration of action and better antifungal activity than the marketed miconazole nitrate formulation.

An orthogonal analytical platform for determining critical material attributes for in situ formation of thermosensitive hyaluronic acid-poly(N-isopropylacrylamide) copolymers

The developability assessment of the in situ formation of thermosensitive injectables requires the unequivocal determination of their lower critical solution temperatures (LCSTs). Herein, we established a standardized threshold for LCST detection by harmonizing and cross-validating the orthogonal methods using techniques such as nuclear magnetic resonance spectroscopy, light scattering, turbidimetry, backgrounded membrane imaging, and rheology. The selected techniques were in agreement and promptly disclosed unique features and instrumental biases of otherwise difficult interpretations in the characterization of thermosensitive polymers. Thus, various hyaluronic acid–poly(N-isopropylacrylamide) copolymers were synthesized via strain-promoted azide–alkyne cycloaddition to understand their critical material attributes. Structure–function relationships and behaviors of the copolymers were tested under in vitro-simulated in vivo conditions.

Influence of Poly(Ethylene Glycol) Dimethacrylates’ Chain Length on Electrical Conductivity and Other Selected Physicochemical Properties of Thermally Sensitive N-isopropylacrylamide Derivatives

Thermosensitive polymers P1–P6 of N-isopropylacrylamide (PNIPA) and poly(ethylene glycol) dimethacrylates (PEGDMAs), av. Mn 550–20,000, were synthesized via surfactant-free precipitation polymerization (SFPP) using ammonium persulfate (APS) at 70 °C. The polymerization course was monitored by the conductivity. The hydrodynamic diameters (HDs) and the polydispersity indexes (PDIs) of the aqueous dispersion of P1–P6 in the 18–45 °C range, assessed via dynamic light scattering (DLS), were at 18° as follows (nm): 73.95 ± 19.51 (PDI 0.57 ± 0.08), 74.62 ± 0.76 (PDI 0.56 ± 0,01), 69.45 ± 1.47 (PDI 0.57 ± 0.03), 196.2 ± 2.50 (PDI 0.53 ± 0.04), 194.30 ± 3.36 (PDI 0.56 ± 0.04), 81.99 ± 0.53 (PDI 0.56 ± 0.01), 76.87 ± 0.30 (PDI 0.54 ± 0.01), respectively. The electrophoretic mobilities estimated the zeta potential (ZP) in the 18–45 °C range, and at 18 °C they were as follows (mV): −2.57 ± 0.10, −4.32 ± 0.67, −5.34 ± 0.95, −-3.02 ± 0.76, −4.71 ± 2.69, −2.30 ± 0.36, −2.86 ± 0.42 for polymer dispersion P1–P6. The polymers were characterized by attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR), H nuclear magnetic resonance (1H NMR), thermogravimetric analysis (TG/DTA), Differential Scanning Calorimetry (DSC), and powder X-ray diffraction analysis (PXRD). The length of the cross-linker chain influences the physicochemical properties of the obtained polymers.

Engineering Entomopathogenic Fungi Using Thermal-Responsive Polymer to Boost Their Resilience against Abiotic Stresses.

Entomopathogenic fungi offer an ecologically sustainable and highly effective alternative to chemical pesticides for managing plant pests. However, the efficacy of mycoinsecticides in pest control suffers from environmental abiotic stresses, such as solar UV radiation and temperature fluctuations, which seriously hinder their practical application in the field. Herein, we discovered that the synthetic amphiphilic thermal-responsive polymers are able to significantly enhance the resistance of Metarhizium robertsii conidia against thermal and UV irradiation stresses. The thermosensitive polymers with extremely low cytotoxicity and good biocompatibility can be engineered onto the M. robertsii conidia surface by anchoring hydrophobic alkyl chains. Further investigations revealed that polymer supplementation remarkably augmented the capacity for penetration and the virulence of M. robertsii under heat and UV stresses. Notably, broad-spectrum entomopathogenic fungi can be protected by the polymers. The molecular mechanism was elucidated through exploring RNA sequencing and in vivo/vitro enzyme activity assays. This work provides a novel avenue for fortifying the resilience of entomopathogenic fungi, potentially advancing their practical application as biopesticides.

Glatiramer acetate in situ forming gel, a new approach for multiple sclerosis treatment.

Glatiramer acetate (GA), a commonly used treatment for multiple sclerosis (MS), requires long-term frequent injections to ensure its effectiveness. This often leads to adverse effects, patient noncompliance, and economic inefficiency. In this study, poloxamer, as a thermosensitive polymer modified by chitosan (CS) and hyaluronic acid (HA), was employed to prepare an in situ forming prolonged release formulation of GA to overcome the problems derived from frequent repeated injections and to enhance the patient compliance. The sol-gel formulation was produced through a cold method and optimized using design of experiments. The final product was characterized in terms of gelation time (GT), rheological behaviors, morphological properties, assay, and drug release kinetics. The in vitro release rate of GA during the first 24 h was quite rapid, but then it continued at a slower rate of 0.05 mg ml-1h-1. The in vivo analysis after the subcutaneous injections showed lower levels of IL-5, IL-13, and uric acid (UA) in mice treated with the gel formulation compared with those receiving free GA in the first few days. However, after 10 days, significantly higher concentrations were detected, which continued to increase slowly. It can be concluded that the designed thermosensitive sol-gel formula is capable of extending the effectiveness of GA and can be considered as a promising sustained release formulation for the treatment of MS.

Preparation of a surface molecularly imprinted thermo-sensitive polymer for selective trypsin capture

Molecularly imprinted polymers (MIPs) are innovative porous materials created through polymerization templating methods for highly selective, sensitive detection and separation of the desired chemical species, known as template molecules. Surface imprinting over nano-sized substrates with special functional groups is an effective approach for improving the mass transfer and rebinding capacity. In this study, we successfully performed surface imprinting using methacrylic acid (MAA) and thermoresponsive N-isopropyl acrylamide (NIPAm) as functional monomers on acrylic-functionalized silica nanoparticles and served as a Trypsin artificial receptor. The resulting Trypsin imprinted polymer exhibited a binding capacity of 1022.44 mg/g, surpassing the non-imprinted polymer’s capacity of 292.41 mg/g within 45 min. Moreover, the imprinting factor, the main influence factor in MIP performance, was 3.5, demonstrating the significant selectivity of the polymeric products. In addition, due to the temperature sensitivity of NIPAm the template removing process was simply done by changing pore size. The silica nanoparticles and the synthesized MIP particles had diameters of approximately 95 nm and 105 nm, respectively, with the polymer layer thickness being around 5 nm. The MIP adsorption model followed the Freundlich isotherm and pseudo-second-order kinetics resulting in efficiencies of 93.0 % and 95.4 %, respectively. The developed Trypsin imprinted polymer was reusable for four consecutive uses,demonstrating both resilience and selectivity towards Trypsin.

Development of an Intranasal In Situ System for Ribavirin Delivery: In Vitro and In Vivo Evaluation.

Recently, ribavirin has demonstrated effectiveness in treating glioblastoma through intranasal administration utilizing the nose-to-brain delivery route. Enhancing ribavirin's bioavailability can be achieved by utilizing intranasal stimuli-responsive systems that create a gel on the nasal mucosa. The research examined thermosensitive, pH-sensitive, and ion-selective polymers in various combinations and concentrations, chosen in line with the current Quality by Design (QbD) approach in pharmaceutical development. Following a thorough assessment of key parameters, the optimal composition of gellan gum at 0.5%, Poloxamer 124 at 2%, and purified water with ribavirin concentration at 100 mg/mL was formulated and subjected to in vivo testing. Through experiments on male rats, the nose-to-brain penetration mechanism of the active pharmaceutical ingredient (API) was elucidated, showcasing drug accumulation in the olfactory bulbs and brain.

Contemporary directions in the therapy of sensory hearing loss

<b>Introduction:</b> More than 5% of the world’s population experience hearing impairment. The most common form is presbycusis (age-related hearing loss; ARHL). It affects almost one in three people over the age of 65. The hair cells of the cochlea play an important role in the process of sound registration. Genetic mutations, aging and environmental factors can cause damage that contributes to the hearing loss.<b>Methods and results:</b> The currently explored research directions include drug treatments, gene therapies, and stem cell therapies. To date, no significant differences in the therapeutic effect depending on the route of corticosteroid administration have been demonstrated in patients with moderate to severe hearing loss. New dexamethasone-containing hydrogel formulations, as well as lipid formulations, thermosensitive polymers, and nanoparticles, have been developed to achieve high drug concentrations in the inner ear structures. Otoprotective effects of antioxidants or substances that modify the toxic effects of e.g. cisplatin, are also being studied. Attempts at auditory cells’ regeneration seem promising in hearing loss research. Substances that regulate the central mechanisms of the Notch and Wnt pathways are being explored to this end. The genetic determinants of presbycusis suggest that interference at the level of specific genes may be a promising option for the treatment of this condition. With the CRISPR/Cas9 technology, the functions of inner ear genes can be effectively studied by disrupting normal gene alleles. The CRISPR/Cas9 complexes developed to target specific genes are delivered using cationic lipids, proteins, and viral vectors. They are then transported through the round window membrane by diffusion, without the need to surgically disrupt the inner ear. The potential of using antisense oligonucleotides to treat hereditary deafness caused by hair cell degeneration has also been established. Another research direction is related to stem cells being used for the development of in vitro 3D models of the human inner ear. Studies are also pursued to identify the mechanisms underlying the formation of cochlear organoids from pluripotent cells as well as determine the critical time points and events for cochlear sensory epithelial development and targeted hair cell differentiation.<b>Conclusions:</b> In summary, significant progress has been made over the past decade in the search for novel therapies for sensory hearing loss. This line of research remains an ambitious and important area for further exploration.

Temperature- and pH-induced dual-crosslinked methylcellulose/chitosan-gallol conjugate composite hydrogels with improved mechanical, tissue adhesive, and hemostatic properties

Gauze or bandages are commonly used to effectively control bleeding during trauma and surgery. However, conventional treatment methods can sometimes lead to secondary damages. In recent years, there has been increased interest in developing adhesive hemostatic hydrogels as a safer alternative for achieving hemostasis. Methylcellulose (MC) is a well-known thermo-sensitive polymer with excellent biocompatibility that is capable of forming a hydrogel through physical crosslinking owing to its inherent thermo-reversible properties. However, the poor mechanical properties of the MC hydrogel comprising a single crosslinked network (SN) limit its application as a hemostatic material. To address this issue, we incorporated a chitosan-gallol (CS-GA) conjugate, which has the ability to form chemical crosslinks through self-crosslinking reactions under specific pH conditions, into the MC hydrogel to reinforce the MC hydrogel network. The resulting MC/CS-GA hydrogel with a dual-crosslinked network (DN), involving both physical and chemical crosslinks, exhibited synergistic effects of the two types of crosslinks. Thus, compared with those of the SN hydrogel, the composite DN hydrogel exhibited significantly enhanced mechanical strength and tissue adhesive properties. Moreover, the DN hydrogel presented excellent biological activity in vitro. Additionally, in rat hepatic hemorrhage models, the DN hydrogel exhibited high hemostatic efficiency, showcasing its multifunctional capabilities.

Temperature‐Activated Near‐Infrared‐II Fluorescence and SERS Dynamic‐Reversible Probes for Long‐Term Assessment of Osteoarthritis In Vivo

AbstractThe abnormal fluctuation of temperature in vivo usually reflects the progression of inflammatory diseases. Noninvasive, real‐time, and accurate monitoring and imaging of temperature variation in vivo is advantageous for guiding the early diagnosis and treatment of disease, but it remains difficult to achieve. Herein, we developed a temperature‐activated near‐infrared‐II fluorescence (NIR‐II FL) and surface‐enhanced Raman scattering (SERS) nanoprobe for long‐term monitoring of temperature changes in rat arthritis and timely assessment of the status of osteoarthritis. The thermosensitive polymer bearing NIR‐II FL dye was grafted onto the surface of nanoporous core‐satellite gold nanostructures to form the nanoprobe, wherein the nanoprobe contains NIR‐II FL and Raman reference signals that are independent of temperature change. The ratiometric FL1150/FL1550 and S1528/S2226 values of the nanoprobe exhibited a reversible conversion with temperature changes. The nanoprobe accurately distinguishes the temperature variations in the inflamed joint versus the normal joint in vivo by ratiometric FL and SERS imaging, allowing for an accurate diagnosis of inflammation. Meanwhile, it can continuously monitor fluctuations in temperature over an extended period during the onset and treatment of inflammation. The tested temperature change trend could be used as an indicator for early diagnosis of inflammation and real‐time evaluation of therapeutic effects.

Temperature-Activated Near-Infrared-II Fluorescence and SERS Dynamic-Reversible Probes for Long-Term Assessment of Osteoarthritis In Vivo.

The abnormal fluctuation of temperature in vivo usually reflects the progression of inflammatory diseases. Noninvasive, real-time, and accurate monitoring and imaging of temperature variation in vivo is advantageous for guiding the early diagnosis and treatment of disease, but it remains difficult to achieve. Herein, we developed a temperature-activated near-infrared-II fluorescence (NIR-II FL) and surface-enhanced Raman scattering (SERS) nanoprobe for long-term monitoring of temperature changes in rat arthritis and timely assessment of the status of osteoarthritis. The thermosensitive polymer bearing NIR-II FL dye was grafted onto the surface of nanoporous core-satellite gold nanostructures to form the nanoprobe, wherein the nanoprobe contains NIR-II FL and Raman reference signals that are independent of temperature change. The ratiometric FL1150/FL1550 and S1528/S2226 values of the nanoprobe exhibited a reversible conversion with temperature changes. The nanoprobe accurately distinguishes the temperature variations in the inflamed joint versus the normal joint in vivo by ratiometric FL and SERS imaging, allowing for an accurate diagnosis of inflammation. Meanwhile, it can continuously monitor fluctuations in temperature over an extended period during the onset and treatment of inflammation. The tested temperature change trend could be used as an indicator for early diagnosis of inflammation and real-time evaluation of therapeutic effects.

Paravertebrally-Injected Multifunctional Hydrogel for Sustained Anti-Inflammation and Pain Relief in Lumbar Disc Herniation.

Pain caused by lumbar disc herniation (LDH) severely compromises patients' quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH-induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally-injected multifunctional hydrogel that can efficiently co-load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti-inflammation, reactive oxygen species (ROS)-removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS-responsive crosslinker to form amphiphilic polymer that self-assemble into particles with ropivacaine loaded into the core. Solution of drug-loaded particles and thermo-sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro-inflammatory cytokines and pain-related molecules including cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Therapeutic hydrogel suppresses the LDH-induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine-related diseases.

Spreading dynamics of a microgel particle-laden thermosensitive polymer drop along smooth and nanofiber surfaces

The research focuses on the influence of 300-μm microgel particles in an aqueous solution of a thermosensitive biopolymer on the spreading and deformation of 3.7-mm drops. The drops impact a smooth hydrophilic and a rough hydrophobic surface. A mass fraction of microgel particles varies in a range of 0–0.2. A universal physical model of the spreading of thermosensitive polymer drops laden with microgel particles along surfaces with significantly different roughness is proposed. It explains the strong inhomogeneity of the contact line stretching due to the deceleration of the continuous phase flow by microgel particles and the increased flow vorticity because of the addition of the surface roughness factor. The validity of the proposed physical model is proven by qualitative and quantitative assessments of the contact line deformation when spreading. An empirical expression for the maximum spreading factor is derived, taking into account the properties of liquids, wall roughness, and microgel particle concentration; it reliably predicts when Re≈110−3100, the surface roughness is 0.5–125 nm, Ca=4.5×10−7, and the number of microgel particles in drops is up to 100. The expression was successfully tested during the modeling of arbitrary surface roughness and the increased concentration of microgel particles relative to those considered in experiments during the formation of a biopolymer layer. When developing the method of additive manufacturing of a functional layer, a practical correlation was established between the volume content of microgel particles, acting as potential containers for living cells, in a drop and the area of the biopolymer layer.

Enhancement of Solubility by Hydrotropic Techniques of Lercanidipine HCl: In-situ Nasal Gel Development

Lercanidipine HCl is a novel, third-generation, potent, vasoselective 1, 4- dihydropyridine calcium channel antagonist and a Biopharmaceutical Classification System (BCS) class II drug that aids in preventing hypertension. The final aim of the present work was to promote the solubility of lercanidipine HCl via hydrotrophy and then include it in the in-situ gel formulation. This enhancement of drug solubility was carried out by using citric acid as a hydrotropic agent. Simultaneously, using a mixture of two polymers, namely Poloxamer 407, a thermosensitive polymer with reversible thermal characteristics. Carbopol 940P is a high-viscosity builder exploited for developing in-situ gel. The optimization of preliminary batches of mixtures of both polymers was highly accepted by using 32 factorial designs. F4 was found to be highly optimized, according to all the evaluation parameters and Poloxamer 407 (18% w/v) and Carbopol 940P (0.2% w/v), with drug release of 93.23%. Goat mucosa ex-vivo investigation yielded a value of 79.14% flux at 6 hours. According to ICH guidance, the in-situ Lercanidipine HCl gel has turned up to be stable following a 6-month stability investigation. Thus, the subsequent thermoreversible in-situ gel was scouted to act as a potent nasal distributor with greater bioavailability and patient compliance for the nasal medication.

Preparation of Thermosensitive Polymer Immobilized Horseradish Peroxidase and its Application in Catalytic Degradation of Phenol

Preparation of Thermosensitive Polymer Immobilized Horseradish Peroxidase and its Application in Catalytic Degradation of Phenol

Poly(2-isopropenyl-2-oxazoline) as a Versatile Functional Polymer for Biomedical Applications.

Functional polymers play an important role in various biomedical applications. From many choices, poly(2-isopropenyl-2-oxazoline) (PIPOx) represents a promising reactive polymer with great potential in various biomedical applications. PIPOx, with pendant reactive 2-oxazoline groups, can be readily prepared in a controllable manner via several controlled/living polymerization methods, such as living anionic polymerization, atom transfer radical polymerization (ATRP), reversible addition-fragmentation transfer (RAFT) or rare earth metal-mediated group transfer polymerization. The reactivity of pendant 2-oxazoline allows selective reactions with thiol and carboxylic group-containing compounds without the presence of any catalyst. Moreover, PIPOx has been demonstrated to be a non-cytotoxic polymer with immunomodulative properties. Post-polymerization functionalization of PIPOx has been used for the preparation of thermosensitive or cationic polymers, drug conjugates, hydrogels, brush-like materials, and polymer coatings available for drug and gene delivery, tissue engineering, blood-like materials, antimicrobial materials, and many others. This mini-review covers new achievements in PIPOx synthesis, reactivity, and use in biomedical applications.

The Method of Direct and Reverse Phase Portraits as a Tool for Systematizing the Results of Studies of Phase Transitions in Solutions of Thermosensitive Polymers.

It is shown that a more than significant amount of experimental data obtained in the field of studying systems based on thermosensitive hydrophilic polymers and reflected in the literature over the past decades makes the issue of their systematization and classification relevant. This, in turn, makes relevant the question of choosing the appropriate classification criteria. It is shown that the basic classification feature can be the number of phase transition stages, which can vary from one to four or more depending on the nature of the temperature-sensitive system. In this work, the method of inverse phase portraits is proposed for the first time. It was intended, among other things, to identify the number of phase transition stages. Moreover, the accuracy of this method significantly exceeds the accuracy of the previously used method of direct phase portraits since, for the first time, the operation of numerical differentiation is replaced by the operation of numerical integration. A specific example of the application of the proposed method for the analysis of a previously studied temperature-sensitive system is presented. It is shown that this method also allows for a quantitative comparison between the results obtained by the differential calorimetry method and the turbidimetry method. Issues related to increasing the resolution of the method of direct phase portraits are discussed.