REVIEW ON: RECENT ADVANCES IN THE STATE OF THE ART OF IN SITU FORMING INJECTABLE HYDROGEL SYSTEMS FOR THERAPEUTIC APPLICATIONS. (original) (raw)
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Injectable polymeric hydrogels for the delivery of therapeutic agents: A review
European Polymer Journal, 2015
Since drug delivery systems have become one of the most promising areas of human health related research, the applications of biomaterials such as hydrogels have been widely investigated. Possessing unique hydrophilic, biocompatible network structures and the ability to form solid-like gel states once administered, injectable hydrogels facilitate the encapsulation and release of therapeutic agents, including drugs, proteins, genes and cells, in a controllable manner. A wide and diverse range of techniques have been used to generate hydrogels, from chemical cross-linking, such as photo-polymerization, click chemistry, enzyme-catalyzed reactions, Schiff's base reactions, and thiol-based Michael reactions, to physical cross-linking induced by temperature, pH, ionic interaction, guesthost inclusion, stereo-complexation or complementary binding. This review covers the utilization of various injectable hydrogel systems for the delivery of therapeutic agents from the viewpoint of cross-linking methods.
Self‐assembling cyclodextrin based hydrogels for the sustained delivery of hydrophobic drugs
Journal of Biomedical Materials Research Part A, 2008
This study aims to investigate the rheological properties of self-assembling gels containing cyclodextrins with potential application as injectable matrix for the sustained delivery of poorly soluble drugs. The ability of these gels to entrap two hydrophobic molecules, benzophenone (BZ) and tamoxifen (TM), and to allow their in vitro sustained release was evaluated. In view of their future pharmaceutical use, gels were sterilized by high hydrostatic pressures (HHP) and tested for their biocompatibility. The gels formed instantaneously at room temperature, by mixing the aqueous solutions of two polymers: a b-cyclodextrin polymer (pbCD) and a hydrophobically modified dextran by grafting alkyl side chains (MD). MD-pbCD gels presented a viscoelastic behavior under low shear, characterized by constant values of the loss modulus G 00 and the storage modulus G 0 . The most stable gels were obtained for a total polymer concentration C p of 6.6% and 7.5% (w/w), and a polymer ratio MD/pbCD of 50/50 and 33/67 (w/w). BZ and TM were successfully incorporated into MD-pbCD gels with loading efficiencies as high as 90%. In vitro, TM and BZ were released gradually from the gel matrix with less than 25% and 75% release, respectively, after 6 days incubation. HHP treatment did not modify the rheological characteristics of MD-pbCD gels. Moreover, the low toxicity of these gels after intramuscular administration in rabbits makes them promising injectable devices for local delivery of drugs.
In situ Crosslinkable Thiol-ene Hydrogels Based on PEGylated Chitosan and β-Cyclodextrin
Journal of the Turkish Chemical Society, Section A: Chemistry, 2018
Novel β-Cyclodextrin incorporated injectable hydrogels employing PEGylated chitosan as biobased hydrophilic matrix have been fabricated via thiol-ene reaction. As thiol bearing polymer counterpart of hydrogel precursors, native chitosan was firstly modified with polyethylene glycol groups to increase its water solubility and bioinertness and then decorated with thiol groups to facilitate thiol-ene crosslinking with acryloyl-modified β-cyclodextrin. A series of hydrogels with varying amounts of acryloyl β-CD and PEGylated chitosan feed were synthesized with high efficiency under mild aqueous conditions. The resulting hydrogels were characterized by equilibrium swelling, structural morphology and rheology. These materials were investigated as controlled drug release platforms by employing a poorly water soluble anti-inflammatory drug diclofenac as model compound. Benefiting from the inclusion complex formation of the drug with β-CD groups in gel interior, prolonged release profiles were maintained. The total drug absorption and release of hydrogels were shown to be dependent on the amount of β-CD in gel matrix. These hydrogels combined efficient crosslinking and β-CD incorporation into clinically important chitosan scaffold and might have potential applications as injectable drug reservoirs such as in regenerative tissue engineering.
Injectable, Mixed Natural-Synthetic Polymer Hydrogels with Modular Properties
Biomacromolecules, 2012
A series of synthetic oligomers (based on the thermosensitive polymer poly(N-isopropylacrylamide) and carbohydrate polymers (including hyaluronic acid, carboxymethyl cellulose, dextran, and methylcellulose) were functionalized with hydrazide or aldehyde functional groups and mixed using a double-barreled syringe to create in situ gelling, hydrazone-cross-linked hydrogels. By mixing different numbers and ratios of different reactive oligomer or polymer precursors, covalently cross-linked hydrogel networks comprised of different polymeric components are produced by simple mixing of reactive components, without the need for any intermediate chemistries (e.g., grafting). In this way, hydrogels with defined swelling, degradation, phase transition, drug binding, and mechanical properties can be produced with properties intermediate to those of the mixture of reactive precursor polymers selected. When this modular mixing approach is used, one property can (in many cases) be selectively modified while keeping other properties constant, providing a highly adaptable method of engineering injectable, rapidly gelling hydrogels for potential in vivo applications.
International journal of Pharmacy and Pharmaceutical Sciences, 2014
Objective: The development of injectable and stable hydrogels for protein delivery is a major challenge. Therefore, the objective of this study was to evaluate the potential of polymerized β-CD for the formulation of stable hydrogels suitable for loading and release of bioactive agents and to investigate the mechanism of hydrogel formation. Methods: Hydrogels based on the inclusion complexation of polymerized β-cyclodextrin and cholesterol terminated poly(ethylene glycol) polymers were formed by rehydration of a lyophilized mixture of both polymers. The mechanism of hydrogel formation was investigated via isothermal titration calorimetry, fluorescence spectroscopy and dynamic light scattering measurements. The release behavior of bovine serum albumin (BSA) as a model protein from the modified gels was explored. Results: Rheological analysis demonstrated that the prepared hydrogels had a viscoelastic behavior even at elevated temperature (> 37 ˚C). There are two competing mechanisms for hydrogel formation. The first mechanism is the inclusion complexation between cholesterol moieties and β-CD cavities. The second one is the self association of cholesterol modified PEGs. β-CD had the ability to dissociate the PEG-cholesterol associations. The quantitative and complete release of BSA was observed within 4 weeks. Conclusion: The polymerized form of β-CD, rather than native β-CD is essential for the formation of stable hydrogels. These results were supported by the ability of the modified hydrogel system for loading and release of BSA, making such hydrogel systems promising devices in drug delivery applications.
Injectable Electroactive Hydrogels Formed via Host–Guest Interactions
Injectable conducting hydrogels (ICHs) are promising conductive materials in biomedicine and bioengineering fields. However, the synthesis of ICHs in previous work involved chemical cross-linking, and this may result in biocompatibility problems of the hydrogels. We present the successful synthesis of ICHs via noncovalent host−guest interactions, avoiding the side effect of covalent chemical crosslinking. The ICHs are based on the γ-cyclodextrin dimer as the host molecule and tetraaniline and poly(ethylene glycol) as the guests in a synthetic well-defined hydrophilic copolymer. The sol−gel transition mechanism of the in situ hydrogel is thoroughly investigated. This novel synthesis approach of ICHs via supramolecular chemistry will lead to various new biomedical applications for conducting polymers.