Physical Gels Research Articles

Enhancing Mucoadhesive Properties of Gelatin through Chemical Modification with Unsaturated Anhydrides.

Gelatin is a water-soluble natural polyampholyte with poor mucoadhesive properties. It has traditionally been used as a major ingredient in many pharmaceuticals, including soft and hard capsules, suppositories, tissue engineering, and regenerative medicine. The mucoadhesive properties of gelatin can be improved by modifying it through conjugation with specific adhesive unsaturated groups. In this study, gelatin was modified by reacting with crotonic, itaconic, and methacrylic anhydrides in varying molar ratios to yield crotonoylated-, itaconoylated-, and methacryloylated gelatins (abbreviated as Gel-CA, Gel-IA, and Gel-MA, respectively). The successful synthesis was confirmed using 1H NMR, FTIR spectroscopies, and colorimetric TNBSA assay. The effect of chemical modification on the isoelectric point was studied through viscosity and electrophoretic mobility measurements. The evolution of the storage (G') and loss (G'') moduli was employed to determine thermoreversible gelation points of modified and unmodified gelatins. The safety of modified gelatin derivatives was assessed with an in vivo slug mucosal irritation test (SMIT) and an in vitro MTT assay utilizing human pulmonary fibroblasts cell line. Two different model dosage forms, such as physical gels and spray-dried microparticles, were prepared and their mucoadhesive properties were evaluated using a flow-through technique with fluorescent detection and a tensile test with ex vivo porcine vaginal tissues and sheep nasal mucosa. Gelatins modified with unsaturated groups exhibited superior mucoadhesive properties compared to native gelatin. The enhanced ability of gelatin modified with these unsaturated functional groups is due to the formation of covalent bonds with cysteine-rich subdomains present in the mucin via thiol-ene click Michael-type addition reactions occurring under physiologically relevant conditions.

Responsive Properties of Bis-urea-based Supramolecular Hydrogels

Physical hydrogels exhibit sol-gel reversibility, which is affected by external stimuli such as variations in pH and temperature. One class of hydrogelators, known as the low-molecular- weight gelators, can form fibrillar networks through noncovalent self-assembly, resulting in the formation of physical gels. This study aims to investigate the pH-responsive properties of bis-urea-based supramolecular hydrogelators. A series of bis-urea compounds containing an aromatic linker and various end groups were synthesized via a one-pot condensation reaction. Gelation of the compounds in water was conducted at pH 2–13, whereby the inversion technique was used to confirm the hydrogel formation. The compound bearing an m-picolyl end group effectively forms gels within the pH 3–12 range. The gelator also exhibits decreasing critical gel concentration with increasing pH, presumably due to the ionizability of the pyridyl groups. Rheological analysis of the gels determined the storage modulus (G’) to be greater than the loss modulus (G”), which indicated the expected solid-like behavior of the hydrogel at low strain. The morphology of the gel obtained by scanning electron microscopy revealed a fibrous aggregated structure. Results obtained from this study may suggest the applicability of bis-urea compounds as pH-sensitive physical hydrogelators.

Deionization-induced colorless transparency in physical gels formed by clay aqueous dispersions

Physical gels formed by aqueous clay dispersion are typically turbid and have a milky appearance. The colorless and transparent nature of gels expands the potential for novel applications. In this study, we successfully produced a transparent gel by deionizing the gel as much as possible while maintaining its dynamic elastic modulus, akin to water. The aqueous clay suspensions exhibited specific sol-gel regions corresponding to the type of clay. According to images obtained through cryo-SEM, the three-dimensional network formed by clay became finer when deionization was carried out, and the aqueous dispersion exhibited Rayleigh scattering. The reduction in the extent of Mie scattering due to the suppression of clay aggregation through deionization results in its colorless transparency. This transparent gel will open up various potential applications, including 3D printing support structures, 3D cell culture, 3D art and displays with dispersed materials, educational materials with visual effects, enhancing traditional products, and innovative engineering applications.

Competition among physical, chemical, and hybrid gelation mechanisms in biopolymers.

Depending on how they form their linkages, biopolymer gelatin gels are commonly classified as physical, chemical, or hybrid; in gelatin hybrid gels, the physical and chemical crosslinking mechanisms occur simultaneously. The viscoelastic behavior of gels following different gelation processes was determined around the gel point. Their gel fractal dimensions were obtained using the BST-scaling model from large amplitude oscillatory shear results. The fractal dimension of hybrid gels is between 1.46 and 1.60, depending on the dominant crosslinking process. The main features of the Lissajous-Bowditch curves were determined for maturated gels that follow different gelation processes, and it is possible to observe the dominant gelation mechanism. The gelation kinetics process is followed by measuring the mean squared displacement (MSD) of microspheres embedded in gelatin solutions using diffusion wave spectroscopy, which in turn allows evaluating G'(ω) and G''(ω), the persistence length, and the mesh size as a function of time throughout the gelation process. The MSD, as a function of elapsed time from the start of the gelation process, follows a behavior that depends on the gelation processes. As time elapses after gelation starts, the persistence length of the unstructured, non-bonded flexible polymer sections decreases due to the formation of bonds. In the hybrid case, it is not a mixture of both processes; they are not independent when occurring simultaneously. The time evolution of the gel network's mesh size roughly follows an exponential decay.

Low solid content mouldable chitin physical hydrogel prepared by atypical rupture-free swelling.

In this study, the atypical swelling gelation of chitin physical hydrogels was investigated. Just by tuning the amount of the N-acetylation reagent, the degree of acetylation varied and mouldable chitin hydrogels with a wide variety of gel concentrations (0.2-6.4 wt%) were obtained. In response to the gel concentration, the mechanical properties ranged from swollen soft gels to shrunken rigid gels (compressive moduli of 4-310 kPa). The thus-prepared chitin hydrogels, which were composed of only chitin and water, exhibited high transparency and integrity. The swelling gelation of chitin physical hydrogels was achieved owing to both the positive charges of the amino groups inducing the osmotic pressure and the toughness of the crystalline nanofibrous network structure of the chitin hydrogels that endured the large volume change. These previously unnoticed advantageous aspects of chitin have pioneered a novel area of swellable physical gels that has been exclusive to chemical gels so far.

Designing thermoreversible gels for extended release of mosquito repellent.

Mosquito-borne diseases are responsible for 700 000 deaths annually. Current outdoor protective strategies primarily focus on direct skin application of commercial repellents (i.e., aerosol sprays or topical lotions) which are typically limited to efficacy times of ≤10 hours due to rapid evaporation and dermal absorption. Consequently, frequent reapplication for continuous protection can increase associated health hazards and cause noncompliance. This study utilizes Hansen solubility parameter modeling to design physical gels composed of insect-repelling N,N-diethyl-meta-toluamide (DEET) and modacrylic copolymer poly(acrylonitrile-co-vinyl chloride) (P(AN-VC)). The P(AN-VC)/DEET composites exhibit tunable and reversible sol-gel transition temperatures that can meet the thermomechanical stability demands of the intended application and permit facile transition to commercial melt processing techniques such as injection molding, filament spinning, or film casting. P(AN-VC)/DEET gel films demonstrate mosquito repellency for more than half a year-performing longer than any other known material to date-due to the high reservoir of repellent and its desorption hindrance from the polymer matrix. Therefore, P(AN-VC)/DEET gels hold significant potential for extended protection against mosquitos and other biting arthropods.

Ductile-to-brittle transition and yielding in soft amorphous materials: perspectives and open questions.

Soft amorphous materials are viscoelastic solids ubiquitously found around us, from clays and cementitious pastes to emulsions and physical gels encountered in food or biomedical engineering. Under an external deformation, these materials undergo a noteworthy transition from a solid to a liquid state that reshapes the material microstructure. This yielding transition was the main theme of a workshop held from January 9 to 13, 2023 at the Lorentz Center in Leiden. The manuscript presented here offers a critical perspective on the subject, synthesizing insights from the various brainstorming sessions and informal discussions that unfolded during this week of vibrant exchange of ideas. The result of these exchanges takes the form of a series of open questions that represent outstanding experimental, numerical, and theoretical challenges to be tackled in the near future.

Cellulose Nanocrystals As a Key in Wearable Sensors

In recent years, the development of cellulose-based inks for 3D printing has received significant interest due to numerous cellulose and its derivatives properties [1], [2]. Carboxymethyl cellulose (CMC) is an anionic water-soluble cellulose derivative widely used as superabsorbent hydrogels [3]. Another cellulose derivative is cellulose nanocrystal (CNC), a rod-like nanoparticle that can be applied for the mechanical strengthening of hydrogels and also presents potential use in several applications in the biomedical field [2], [4]. Based on this, we have proposed to investigate if CMC and CNC mixtures result in cellulose-based nanocomposite gels suitable for extrusion printing of wearable sensors. Interactions between CNC and CMC resulted in physical gels, where rheological properties and extrusion printing parameters' effects were studied. A Modular Compact Rheometer (Anton Paar MCR-102, Austria) with a plate-plate geometry (50 mm diameter and 1 mm gap) at 25 °C was used to perform rheological measurements. Extrusion printing was performed on the customized 3DCloner Lab printer using a 22G nozzle tip of 25 mm in length and a diameter of 0.70 mm (Injex, Brazil). Gels presented shear-thinning, solid-like viscoelastic behavior, viscosity recovery, and continuous filaments obtained during printing. Moreover, the alignment of rod-like CNC during the printing process can be a key to improving properties. Tests with different print and extrusion speeds evidenced the influence of the wearable sensor's geometry and mechanical properties. Moreover, the low cytotoxicity of CMC/CNC crosslinked hydrogels was confirmed through an MTT assay of fibroblasts. Further testing is being conducted to evaluate the self-healing and conductive properties of the sensors by external stimuli. Moreover, low cytotoxicity to CMC/CNC crosslinked hydrogels was confirmed through an MTT assay of fibroblasts. External stimuli are being applied to evaluate the self-healing and conductive of the sensor printed.

Amphiphilic Low-Molecular-Weight Gelators Bearing β-S-N-Acetylglucosamine Linked to a Tartaric Acid Scaffold: Synthesis, Self-Assembly and Wheat Germ Agglutinin Binding.

The self-assembly of carbohydrate-based amphiphiles can lead to colloidal soft materials such as supramolecular gels featuring highly desirable characteristics like biodegradability and biocompatibility. The report herein presents the synthesis, characterization and supramolecular self-assembly, physical gelation and wheat lectin binding of two structurally related amphiphilic compounds having β-S-N-acetylglucosamine residues linked to a 2,3-diacyl-N,N'-dipropargylated-l-tartaric diamide. A 1-thio-β-N-acetyl-d-glucosamine precursor attached to a conveniently functionalized linker with an azido group was synthesized by means of a one-pot procedure followed by deprotection. A click reaction successfully led to the two amphiphiles, which differed in length of the fatty acid attached to the tartaric acid scaffold. Although both compounds are poorly soluble in water and organic solvents, the difference in terms of hydrophilic moieties provided them with distinct supramolecular gelation properties. While the presence of an octadecyl chain produced a hydrogelator, the dodecadecyl homologue would only form weak gels in DMSO. SEM and rheology experiments confirmed the characteristic fibrillar morphology and viscoelastic properties, in agreement with the presence of physical gels. Both amphiphiles were able to interact reversibly with wheat germ agglutinin (WGA), a lectin that specifically recognizes GlcNAc residues, indicating a potential use in the food industry, as a gluten sensitivity manager, as well as in health-related industries, for example, for drug delivery systems.

Herbal nanogels: Revolutionizing skin cancer therapy through nanotechnology and natural remedies

The escalating global incidence of skin cancer demands innovative therapeutic approaches that balance efficacy and reduced side effects. The convergence of nanotechnology and medicinal research has unveiled herbal nanogels as promising candidates for advancing skin cancer therapy. Skin cancer, comprising diverse malignancies, necessitates novel strategies to enhance treatment outcomes. Nanogels, intricate networks of cross-linked polymers at the nanoscale, have emerged as versatile vehicles for targeted drug delivery. Their ability to encapsulate a range of therapeutic agents and respond to stimuli offers a platform to revolutionize treatment paradigms. The taxonomy of nanogels encompasses physical cross-linked gels, liposome-modified nanogels, micellar nanogels, hybrid nanogels, and chemically cross-linked nanogels, each holding distinctive characteristics suitable for specific applications. The synthesis of nanogels is a precise craft involving techniques like photolithography, micro-moulding, and emulsion methods, enabling control over particle size, morphology, and drug-loading capacity. Stimuli-responsive nanogels present a dynamic facet of this field, exhibiting potential for targeted drug delivery. Noteworthy examples include LHRH-targeted nanogels and nanogels responsive to the intricate microenvironment of bacterial-accumulated tumors. One of the most intriguing developments lies in the fusion of herbal medicine and nanotechnology, paving the way for herbal nanogels. By incorporating bioactive plant-derived compounds into nanogel matrices, these constructs offer a holistic therapeutic approach. The convergence of nanotechnology and herbal medicine in the form of herbal nanogels presents a promising avenue for elevating skin cancer therapy. Through precise drug delivery mechanisms and responsiveness to complex microenvironments, nanogels exhibit a potential to reshape treatment norms. This comprehensive review provides an in-depth roadmap of the evolving landscape of herbal nanogels, illuminating their potential as effective, targeted, and minimally invasive tools for combating skin cancer.

The Effect of Temperature and Shear on the Gelation of Cellulose Nanocrystals in Deep Eutectic Solvents.

With the flourishing development of 3D printing technology, the demand for printing materials has been increasing rapidly in recent years. In particular, physical gels formed by cellulose nanocrystals (CNCs) exhibit suitable shear-thinning behavior, high storage moduli, and high yield stresses for extrusion-based printing. While most studies use water as the dispersing medium to form CNC percolated gels, the dispersing behavior of CNCs in alternative solvents, such as deep eutectic solvents (DESs), has not been fully explored. Especially, DESs have low volatility and good ionic conductivity to form functional ionogels. Precise control of the rheological properties and selection of suitable dispersion processes continue to pose significant challenges. In light of this, we have devised a novel dispersion process employing thermal and shear treatments to facilitate the gelation of CNCs within DESs. A crude dispersion of CNCs in the DES underwent thermal treatment to partially remove the surface sulfate ester on CNCs. As a result, the repulsive force between CNCs decreases. A second shear then significantly increases the strength of CNC/DES gels potentially because of the increased rod-rod contacts. This approach enables the formation of high-strength gels at low concentrations of CNCs. Both thermal treatment and a second shear are crucial to forming strong percolated CNC gels. In short, we showed a simple strategy to facilitate the dispersion and gelation of CNCs for direct ink writing.

Tuning Physical Properties of GelMA Hydrogels through Microarchitecture for Engineering Osteoid Tissue.

Gelatin methacryloyl (GelMA) hydrogels have gained significant attention due to their biocompatibility and tunable properties. Here, a new approach to engineer GelMA-based matrices to mimic the osteoid matrix is provided. Two cross-linking methods were employed to mimic the tissue stiffness: standard cross-linking (SC) based on visible light exposure (VL) and dual cross-linking (DC) involving physical gelation, followed by VL. It was demonstrated that by reducing the GelMA concentration from 10% (G10) to 5% (G5), the dual-cross-linked G5 achieved a compressive modulus of ∼17 kPa and showed the ability to support bone formation, as evidenced by alkaline phosphatase detection over 3 weeks of incubation in osteogenic medium. Moreover, incorporating poly(ethylene) oxide (PEO) into the G5 and G10 samples was found to hinder the fabrication of highly porous hydrogels, leading to compromised cell survival and reduced osteogenic differentiation, as a consequence of incomplete PEO removal.

Critical-Like Gelation Dynamics in Cellulose Nanocrystal Suspensions.

We use time-resolved mechanical spectroscopy to offer a detailed picture of the gelation dynamics of cellulose nanocrystal (CNC) suspensions following shear cessation in the presence of salt. CNCs are charged, rodlike colloids that self-assemble into various phases, including physical gels serving as soft precursors for biosourced composites. Here, a series of linear viscoelastic spectra acquired across the sol-gel transition of CNC suspensions are rescaled onto two master curves that correspond to a viscoelastic liquid state prior to gelation and to a soft solid state after gelation. These two states are separated by a critical gel point, where all rescaling parameters diverge in an asymmetric fashion yet with exponents that obey hyperscaling relations consistent with previous works on isotropic colloids and polymer gels. Upon varying the salt content, we further show that these critical-like dynamics result in both time-connectivity and time-concentration superposition principles.

Starch-Based Hydrogels as a Drug Delivery System in Biomedical Applications.

Starch-based hydrogels have gained significant attention in biomedical applications as a type of drug delivery system due to their biocompatibility, biodegradability, and ability to absorb and release drugs. Starch-based hydrogels can serve as effective carriers for pharmaceutical compounds such as drugs and proteins to develop drug-loaded hydrogel systems, providing controlled release over an extended period. The porous structure of a hydrogel allows for the diffusion of drugs, ensuring sustained and localized delivery to the target site. Moreover, starch-based hydrogels have been used as a powerful option in various biomedical fields, including cancer and infectious disease treatment. In addition, starch-based hydrogels have shown promise in tissue engineering applications since hydrogels can be used as scaffolds or matrices to support cell growth and tissue regeneration. Depending on techniques such as chemical crosslinking or physical gelation, it can create a three-dimensional network structure that tunes its mechanical properties and mimics the extracellular matrix. Starch-based hydrogels can also provide a supportive environment for cell attachment, proliferation, and differentiation to promote specific cellular responses and tissue regeneration processes with the loading of growth factors, cytokines, or other bioactive molecules. In this review, starch-based hydrogels as a versatile platform for various biomedical applications are discussed.

In Situ Gelling Hydroxypropyl Cellulose Formulation Comprising Cannabidiol-Loaded Block Copolymer Micelles for Sustained Drug Delivery.

Cannabidiol (CBD) is a natural terpenophenolic compound with known pharmacological activities, but the poor solubility of CBD in water limits its widespread use in medicine and pharmacy. Polymeric (nano)carriers demonstrated high potential for enhancing the solubility and therapeutic activity of lipophilic drugs such as CBD. Here, we report the elaboration of a novel hydroxypropyl cellulose (HPC)-based in situ gelling formulation for controlled delivery of CBD. In the first stage, nanosized polymeric micelles from poly(ethylene oxide)-block-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone) (PEO-b-P(CyCL-co-CL) diblock copolymers) were used to increase the solubility of CBD in water. Different copolymers were assessed, and the carrier with the highest encapsulation efficiency (EE) and drug loading capacity (DLC) was selected for further elaboration of nanocomposite in situ gel formulations. Next, the sol-to-gel transition behavior of HPC as a function of K2SO4 concentration in the aqueous solution was investigated by microcalorimetry and dynamic oscillatory rheology, and the optimal formulation capable of forming a physical gel under physiological conditions was determined. Finally, injectable nanocomposite hydrogels comprising cannabidiol were fabricated, and their drug release profile and cytotoxicity against human tumor cell lines were evaluated. The in situ gels exhibited prolonged drug release over 12 h, controlled by gel erosion, and the cytotoxicity of formulated cannabidiol was comparable with that of a free drug.

Rheological percolation, gel‐like behavior and electrical conductivity of multi‐walled carbon nanotubes filled ethylene‐vinyl acetate copolymer/acrylonitrile‐butadiene rubber nanocomposites

AbstractReasonable studies on the composite systems containing conductive nanoparticles are very important to manufacture the materials with physico‐mechanical tailor‐made properties. In this work, rheological percolation, gel‐like behavior and electrical properties of multi‐walled carbon nanotubes (MWCNTs) filled ethylene‐co‐vinyl acetate/acrylonitrile‐butadiene copolymer blends containing 0–7 wt% MWCNTs were studied. The Winter‐Chambon criterion validity was evaluated for physical gelation of the system. The rheological and electrical percolation threshold, gel point (Pg), relaxation exponent (n), gel strength (Sg), and the fractal dimension (df) at the gel point were calculated. The formation of physical gel and rheological percolation threshold were both found to occur at 1 wt% MWCNTs concentration. Based on the df value determined, it was revealed that the system behaved similar to the one in which the excluded volume interactions were nearly screened. It was also found that the storage modulus (G′) near the Pg followed a power‐law scaling relationship in the form where is the distance from Pg. The electrical conductivity of the nanocomposites increased with the increase in MWCNTs loading after the nanofillers content surpassed a certain value. A schematic model was proposed to demonstrate the variation of electrical conduction with the increase in MWCNTs concentration. The excluded volume and hard‐core models were also employed to estimate the average aspect ratio of the nanofillers embedded in the system.Highlights Morphology and gel‐like behavior of EVA/NBR/MWCNTs system were studied Winter‐Chambon criterion was found to be valid for the gelation of the system Rheological percolation and gel point were occurred at the same MWCNTs loading It was found excluded volume interactions were nearly screened at gel point A schematic model for microstructure development was suggested for the system

Efficient Hydrolysis of Cottonseed Oil with Amano Lipase Entrapped on Hydrolysed Polyvinyl Alcohol Gel Pellets Optimized via Factorial Design

Abstract: The aim of this study was to obtain the optimum hydrolysis of cottonseed oil via immobilized lipases (Lipases Rhizopus oryzae, SL from Pseudomonas (Burkholderia) cepacia, Amano lipase from Mucor javanica, ANL from Aspergillus niger lipase, TL from Pseudomonas stutzeri, QLM from Alcaligenes sp., Triacylglycerol lipase (EC 3.1.1.3), PL from Alcaligenes sp., AL from lysosomal acid lipase, Candida antarctica (CA), and Candida cylindrea (CC)) on hydrolysed polyvinyl alcohol (PVA) gel pellets. : The production of free fatty acids by the hydrolysis of triglycerides from several sources is an important component in the economic exploitation of naturally produced renewable raw materials. : Herein, various lipases, including Rhizopus oryzea, SL, Amano lipase from Mucor javanica, ANL, TL, QLM, EC, PL, AL, CA, and CC were screened for optimum hydrolysis of cottonseed oil. Following the selection of lipase for hydrolysis of cottonseed oil, transparent PVA gel was synthesized by physical gelation method employing Dimethyl sulfoxide and a water system. In the last step, immobilization of selected lipase i.e. Amano lipase for cotton seed oil was carried out at 4oC for one hour. After successful synthesis and immobilization, the PVA gel was characterized by FTIR and SEM analysis. Finally, factorial design was employed for optimization of experimental variables such as pH, time and amount of cotton seed oil hydrolysis by lipase immobilized PVA. : The obtained results indicated that lipase Amano was found better with higher free fatty acids (FFA) yields (with 98.38%) in 5 hours using 3 g of cottonseed oil, suggesting that PVA immobilized Amano lipase is an efficient catalyst to hydrolyze the cottonseed oil. : The overall study indicated that hydrolysed PVA gel is an effective biocompatible solid support for immobilization of lipases to obtain higher FFA from cottonseed oil following hydrolysis reaction.

Fully Physically Crosslinked Conductive Hydrogel with Ultrastretchability, Transparency, and Self-Healing Properties for Strain Sensors.

Currently, conductive hydrogels have received great attention as flexible strain sensors. However, the preparation of such sensors with integrated stretchability, transparency, and self-healing properties into one gel through a simple method still remains a huge challenge. Here, a fully physically crosslinked double network hydrogel was developed based on poly(hydroxyethyl acrylamide) (PHEAA) and κ-carrageenan (Car). The driving forces for physical gelation were hydrogen bonds, ion bonding, and electrostatic interactions. The resultant PHEAA-Car hydrogel displayed stretchability (1145%) and optical transparency (92%). Meanwhile, the PHEAA-Car hydrogel exhibited a self-healing property at 25 °C. Additionally, the PHEAA-Car hydrogel-based strain sensor could monitor different joint movements. Based on the above functions, the PHEAA-Car hydrogel can be applied in flexible strain sensors.

Thermoresponsive DNA hydrogels through hydrophilic pre-polymer cross-linker and self-assembly

Denatured DNA molecules were used as building blocks to fabricate thermoresponsive hydrogels by cross-linking DNA strands with an isocyanate (NCO) end-capped star-shaped poly(EO-stat-PO) cross-linker. The NCO groups reacted with the amine groups of DNA’s bases through urea links while base pairing between the matching strands of DNA led to the self-assembly of DNA into a three-dimensional hydrogel network. Analysis of the ultrastructure by scanning force microscopy (SFM) revealed the temperature-mediated transition from the rod-to-coil structure as a result of the destabilization of double-stranded DNA (dsDNA) to form a single-stranded DNA (ssDNA), which eventually resulted in a DNA network due to base pairing, along with hairpin loops due to mismatches between nucleotides. Dynamic oscillatory and large deformation creep tests, as well as stress relaxation tests, revealed the formation of robust cross-linked gels: A ten-fold rise in the elastic modulus was observed for the covalent DNA gel compared to the physical gel at the identical DNA concentration. The thermoresponsiveness of the hydrogels was confirmed by a heating–cooling cycle while the non-porous internal morphology of the hydrogel was demonstrated through scanning electron microscopic analysis. Overall, this is the first study showing the fabrication of covalent DNA hydrogels using an NCO-end-capped hydrophilic prepolymer. Such gels have a high potential to be exploited in many fields to benefit from the structural properties of DNA molecules.

Computational Insight of Phase Transformation and Drug Release Behaviour of Doxycycline-Loaded Ibuprofen-Based In-Situ Forming Gel.

This research investigates the gel formation behaviour and drug-controlling performance of doxycycline-loaded ibuprofen-based in-situ forming gels (DH-loaded IBU-based ISGs) for potential applications in periodontal treatment. The investigation begins by exploring the physical properties and gel formation behaviour of the ISGs, with a particular focus on determining their sustained release capabilities. To gain a deeper understanding of the molecular interactions and dynamics within the ISGs, molecular dynamic (MD) simulations are employed. The effects of adding IBU and DH on reducing surface tension and water tolerance properties, thus affecting molecular properties. The phase transformation phenomenon is observed around the interface, where droplets of ISGs move out to the water phase, leading to the precipitation of IBU around the interface. The optimization of drug release profiles ensures sustained local drug release over seven days, with a burst release observed on the first day. Interestingly, different organic solvents show varying abilities to control DH release, with dimethyl sulfoxide (DMSO) demonstrating superior control compared to N-Methyl-2-pyrrolidone (NMP). MD simulations using AMBER20 software provide valuable insights into the movement of individual molecules, as evidenced by root-mean-square deviation (RMSD) values. The addition of IBU to the system results in the retardation of IBU molecule movement, particularly evident in the DMSO series, with the diffusion constant value of DH reducing from 1.2452 to 0.3372 and in the NMP series from 0.3703 to 0.2245 after adding IBU. The RMSD values indicate a reduction in molecule fluctuation of DH, especially in the DMSO system, where it decreases from over 140 to 40 Å. Moreover, their radius of gyration is influenced by IBU, with the DMSO system showing lower values, suggesting an increase in molecular compactness. Notably, the DH-IBU configuration exhibits stable pairing through H-bonding, with a higher amount of H-bonding observed in the DMSO system, which is correlated with the drug retardation efficacy. These significant findings pave the way for the development of phase transformation mechanistic studies and offer new avenues for future design and optimization formulation in the ISG drug delivery systems field.