Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microrheological characterization of covalent adaptable hydrogels for applications in oral delivery.

ABSTRACT: The feasibility of a covalent adaptable hydrogel (CAH) as an oral delivery platform is explored using ?2rheology, microrheology in a microfluidic device. CAH degradation is initiated by physiologically relevant pHs, including incubation at a single pH and consecutively at different pHs. At a single pH, we determine CAH degradation can be tuned by changing the pH, which can be exploited for controlled release. We calculate the critical relaxation exponent, which defines the gel-sol transition and is independent of the degradation pH. We mimic the changing pH environment through part of the gastrointestinal tract (pH 4.3 to 7.4 or pH 7.4 to 4.3) in our microfluidic device. We determine that dynamic material property evolution is consistent with degradation at a single pH. However, the time scale of degradation is reduced by the history of degradation. These investigations inform the design of this material as a new vehicle for targeted delivery.

SUBMITTER: Wu N

PROVIDER: S-EPMC6677256 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Microrheological characterization of covalent adaptable hydrogels for applications in oral delivery.

Wu Nan N Schultz Kelly M KM

Soft matter 20190701 29

The feasibility of a covalent adaptable hydrogel (CAH) as an oral delivery platform is explored using μ2rheology, microrheology in a microfluidic device. CAH degradation is initiated by physiologically relevant pHs, including incubation at a single pH and consecutively at different pHs. At a single pH, we determine CAH degradation can be tuned by changing the pH, which can be exploited for controlled release. We calculate the critical relaxation exponent, which defines the gel-sol transition and ...[more]

PMID: 31282533

Similar Datasets

Microrheological characterization of covalent adaptable hydrogel degradation in response to temporal pH changes that mimic the gastrointestinal tract.

Project description:Covalent adaptable hydrogels (CAHs) reversibly adapt their structure in response to external stimuli, emerging as a new platform for biological applications. Due to the unique and complex nature of these materials, a characterization technique is needed to measure the rheology of these CAHs in biological processes. μ2rheology, microrheology in a microfluidic device, is a technique that can fully characterize real-time CAH degradation in a changing environment, such as the pH environment of the GI tract. This characterization will enable design and tailoring of these materials for controlled and targeted oral drug delivery. Using μ2rheology, we can exchange the fluid environment without sample loss and measure the change in CAH rheological properties. We show degradation kinetics and material property evolution are independent of degradation history. However, the initial cross-link density at each pH exchange can be decreased by degradation history which decreases the time for the CAH to degrade to the gel-sol transition. These results indicate that CAH degradation can be tuned by changing the initial material properties by varying polymer concentration and ratio of functional groups. We also show that μ2rheology will enable the design of new dynamic materials for targeted drug delivery by enabling these materials to be characterized and tailored in vitro.

| S-EPMC7365765 | biostudies-literature

Poly(ethylene glycol) hydrogels with adaptable mechanical and degradation properties for use in biomedical applications.

Project description:Requirements of hydrogels for drug delivery, wound dressings, and surgical implantation can be extensive, including suitable mechanical properties and tailorable degradation time frames. Herein, an adaptable PEG-based hydrogel, whose mechanical properties and degradation rate can be systematically adjusted to meet these criteria by altering simple variables such as the PEG molecular weight, is described. The performance of these hydrogels in three physical manipulations (pushing, pulling, and folding), representative of manipulations that they may undergo during typical biomedical use, is also assessed. While not all of these formulations can withstand these manipulations, a subset did, and it is intended to further optimize these formulations for specific clinical applications. Additionally, the outcomes of the physical manipulation tests indicate that simply having a high modulus does not correlate with biomedical applicability.

| S-EPMC4066198 | biostudies-literature

Recyclable Organocatalyzed Poly(Thiourethane) Covalent Adaptable Networks.

Project description:A new type of tetraphenylborate salts derived from highly basic and nucleophilic amines, namely 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) and triazabicyclodecene (TBD), was applied to the preparation of networked poly(thiourethane)s (PTUs), which showed a vitrimer-like behavior, with higher stress-relaxation rates than PTUs prepared by using dibutyl thin dilaurate (DBTDL) as the catalyst. The use of these salts, which release the amines when heated, instead of the pure amines, allows the formulation to be easily manipulated to prepare any type of samples. The materials prepared from stoichiometric mixtures of hexamethylene diisocyanate (HDI), trithiol (S3) and with a 10% of molar excess of isocyanate or thiol were characterized by FTIR, thermomechanical analysis, thermogravimetry, stress-relaxation tests and tensile tests, thus obtaining a complete thermal and mechanical characterization of the materials. The recycled materials obtained by grinding the original PTUs and hot-pressing the small pieces in the optimized time and temperature conditions were fully characterized by mechanical, thermomechanical and FTIR studies. This allowed us to confirm their recyclability, without appreciable changes in the network structure and performance. From several observations, the dissociative interchange trans-thiocarbamoylation mechanism was evidenced as the main responsible of the topological rearrangements at high temperature, resulting in a vitrimeric-like behavior.

| S-EPMC7761908 | biostudies-literature

Structure-Reactivity-Property Relationships in Covalent Adaptable Networks.

Project description:Polymer networks built out of dynamic covalent bonds offer the potential to translate the control and tunability of chemical reactions to macroscopic physical properties. Under conditions at which these reactions occur, the topology of covalent adaptable networks (CANs) can rearrange, meaning that they can flow, self-heal, be remolded, and respond to stimuli. Materials with these properties are necessary to fields ranging from sustainability to tissue engineering; thus the conditions and time scale of network rearrangement must be compatible with the intended use. The mechanical properties of CANs are based on the thermodynamics and kinetics of their constituent bonds. Therefore, strategies are needed that connect the molecular and macroscopic worlds. In this Perspective, we analyze structure-reactivity-property relationships for several classes of CANs, illustrating both general design principles and the predictive potential of linear free energy relationships (LFERs) applied to CANs. We discuss opportunities in the field to develop quantitative structure-reactivity-property relationships and open challenges.

| S-EPMC9812368 | biostudies-literature

Controlled Electron-Beam Synthesis of Transparent Hydrogels for Drug Delivery Applications.

Project description:In this study, we highlight hydrogels prepared by electron-beam polymerization. In general, the electron-beam-polymerized hydrogels showed improved mechanical and optical transmittances compared to the conventional UV-cured hydrogels. They were more elastic and had a higher crosslinking density. Additionally, they were transparent over a broader wavelength range. The dependence of the mechanical and optical properties of the hydrogels on the number of single differential and total irradiation doses was analyzed in detail. The hydrogels were prepared for usage as a drug delivery material with methylene blue as a drug model. In the first set of experiments, methylene blue was loaded reversibly after the hydrogel synthesis. Electron-beam-polymerized hydrogels incorporated twice as much methylene blue compared to the UV-polymerized gels. Furthermore, the release of the model drug was found to depend on the crosslinking degree of the hydrogels. In addition, electron-beam polymerization enabled the irreversible binding of the drug molecules if they were mixed with monomers before polymerization.

| S-EPMC6473313 | biostudies-literature

Oral Administration of Salecan-Based Hydrogels for Controlled Insulin Delivery.

Project description:We present an improved type of food gum (salecan) based hydrogels for oral delivery of insulin. Structural hydrogel formation was assessed with Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction. We found that the hydrogel modulus, morphology, and swelling properties can be controlled by varying the salecan dose during hydrogel formation. Insulin was introduced into the hydrogel using a swelling-diffusion approach and then further used a drug prototype. In vitro insulin release profiles demonstrated that the release of entrapped insulin was suppressed in acidic conditions but markedly increased at neutral pH. Cell viability and toxicity tests revealed that the salecan hydrogel constructs were biocompatible. Oral administration of insulin-loaded salecan hydrogels in diabetic rats resulted in a sustained decrease of fasting plasma glucose levels over 6 h postadministration. For nondiabetic animals, the relative pharmacological bioavailability of insulin was significantly larger (6.24%, p < 0.05) for insulin-loaded hydrogels compared to free insulin. These results encourage further development of salecan-based hydrogels as vehicles for controlled insulin delivery following oral administration.

| S-EPMC7764162 | biostudies-literature

Adaptable Hydrogels Mediate Cofactor-Assisted Activation of Biomarker-Responsive Drug Delivery via Positive Feedback for Enhanced Tissue Regeneration.

Project description:The targeted and simultaneous delivery of diverse cargoes with vastly different properties by the same vehicle is highly appealing but challenging. Here, a bioactive nanocomposite hydrogel based on hyaluronic acid and self-assembled pamidronate-magnesium nanoparticles for the localized elution and on-demand simultaneous release of bioactive ions and small molecule drugs is described. The obtained nanocomposite hydrogels exhibit excellent injectability and efficient stress relaxation, thereby allowing easy injection and consequent adaptation of hydrogels to bone defects with irregular shapes. Magnesium ions released from the hydrogels promote osteogenic differentiation of the encapsulated human mesenchymal stem cells (hMSCs) and activation of alkaline phosphatase (ALP). The activated ALP subsequently catalyzes the dephosphorylation (activation) of Dex phosphate, a pro-drug of Dex, and expedites the release of Dex from hydrogels to further promote hMSC osteogenesis. This positive feedback circuit governing the activation and release of Dex significantly enhances bone regeneration at the hydrogel implantation sites. The findings suggest that these injectable nanocomposite hydrogels mediate optimized release of diverse therapeutic cargoes and effectively promote in situ bone regeneration via minimally invasive procedures.

| S-EPMC6299823 | biostudies-literature

Recyclable Covalent Adaptable Polystyrene Networks Using Boronates and TetraAzaADamantanes

Project description: Not available

| S-EPMC11250031 | biostudies-literature

Covalent adaptable networks using boronate linkages by incorporating TetraAzaADamantanes

Project description:Boronic esters prepared by condensation of boronic acids and diols have been widely used as dynamic covalent bonds in the synthesis of both discrete assemblies and polymer networks. In this study we investigate the potential of a new dynamic-covalent motif, derived from TetraAzaADamantanes (TAADs), with their adamantane-like triol structure, in boronic ester-based covalent adaptable networks (CANs). The TetraAzaADamantane-boronic ester linkage has recently been reported as a more hydrolytically stable boronic ester variant, while still having a dynamic pH response: small-molecule studies found little exchange at neutral pH, while fast exchange occurred at pH 3.8. In this work, bi- and trifunctional TetraAzaADamantane linkers were synthesised and crosslinked with boronic acids to form rubber-like materials, with a Young’s modulus of 1.75 MPa. The dynamic nature of the TetraAzaADamantane networks was confirmed by stress relaxation experiments, revealing Arrhenius-like behaviour, with a corresponding activation energy of 142 ± 10 kJ/mol. Increasing the crosslinking density of the material from 10% to 33% resulted in reduced relaxation times, as is consistent with a higher degree of crosslinking within the dynamic networks. In contrast to the reported accelerating effect of acid addition to small-molecule TetraAzaADamantane complexes, within the polymer network the addition of acid increased relaxation times, suggesting unanticipated interactions between the acid and the polymer that cannot occur in the corresponding small-molecules analogues. The obtained boronate-TetraAzaADamantane materials were thermally stable up to 150°C. This thermal stability, in combination with the intrinsically dynamic bonds inside the polymer network, allowed these materials to be reprocessed and healed after damage by hot-pressing.

| S-EPMC9995436 | biostudies-literature

Redox-Responsive Resilin-Like Hydrogels for Tissue Engineering and Drug Delivery Applications.

Project description:Resilin, a protein found in insect cuticles, is renowned for its outstanding elastomeric properties. The authors' laboratory previously developed a recombinant protein, which consisted of consensus resilin-like repeats from Anopheles gambiae, and demonstrated its potential in cartilage and vascular engineering. To broaden the versatility of the resilin-like protein, this study utilizes a cleavable crosslinker, which contains a disulfide bond, to develop smart resilin-like hydrogels that are redox-responsive. The hydrogels exhibit a porous structure and a stable storage modulus (G') of ?3 kPa. NIH/3T3 fibroblasts cultured on hydrogels for 24 h have a high viability (>95%). In addition, the redox-responsive hydrogels show significant degradation in a reducing environment (10 mm glutathione (GSH)). The release profiles of fluorescently labeled dextrans encapsulated within the hydrogels are assessed in vitro. For dextran that is estimated to be larger than the mesh size of the gel, faster release is observed in the presence of reducing agents due to degradation of the hydrogel networks. These studies thus demonstrate the potential of using these smart hydrogels in a variety of applications ranging from scaffolds for tissue engineering to drug delivery systems that target the intracellular reductive environments of tumors.

| S-EPMC6776424 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data