In situ forming, resorbable graft copolymer hydrogels providing controlled drug release (original) (raw)
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Sustained Drug Release from Biopolymer-Based Hydrogels and Hydrogel Coatings
Hydrogels - From Tradition to Innovative Platforms with Multiple Applications
Biopolymer based hydrogels are three-dimensional physically or chemically crosslinked polymeric networks based on natural polymers, with an intrinsic hydrophilic character due to their functional groups. They display high water content, softness, flexibility, permeability, and biocompatibility and possess a very high affinity for biological fluids. These properties resemble those of many soft living tissues, which opens up many opportunities in the biomedical field. In this regard, hydrogels provide fine systems for drug delivery and sustained release of drugs. Moreover, biopolymer based hydrogels can be applied as coatings on medical implants in order to enhance the biocompatibility of the implants and to prevent medical conditions. In this chapter we review the latest achievements concerning the use of biopolymeric physical and chemically crosslinked hydrogels as well as hydrogel coatings as sustained drug release platforms.
Characterisation and controlled drug release from novel drug-loaded hydrogels
European Journal of Pharmaceutics and Biopharmaceutics, 2008
Hydrogel based devices belong to the group of swelling controlled drug delivery systems. Temperature responsive poly(N-isopropylacrylamide)-poly(vinylpyrrolidinone) random copolymers were produced by free radical polymerisation, using 1-hydroxycyclohexylphenyketone as an ultraviolet-light sensitive initiator, and poly(ethylene glycol) dimethacrylate as the crosslinking agent (where appropriate). The hydrogels were synthesised to have lower critical solution temperatures (LCST) near body temperature, which is favourable particularly for 'smart' drug delivery applications. Two model drugs (diclofenac sodium and procaine HCl) were entrapped within these xerogels, by incorporating the active agents prior to photopolymerisation. The properties of the placebo samples were contrasted with the drug-loaded copolymers at low levels of drug integration. Modulated differential scanning calorimetry (MDSC), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscopy (AFM) were used to investigate the influence of the drugs incorporated on the solid-state properties of the xerogels. MDSC and swelling studies were carried out to ascertain their effects on the LCST and swelling behaviour of the hydrated samples. In all cases, drug dissolution analysis showed that the active agent was released at a slower rate at temperatures above the phase transition temperature. Finally, preliminary in vitro cytotoxicity evaluations were performed to establish the toxicological pattern of the gels.
Degradable and Injectable Hydrogel for Drug Delivery in Soft Tissues
Biomacromolecules, 2018
Injectable hydrogels are promising platforms for tissue engineering and local drug delivery as they allow minimal invasiveness. We have here developed an injectable and biodegradable hydrogel based on an amphiphilic PNIPAAm-b-PLA-b-PEG-b-PLA-b-PNIPAAm pentablock synthesized by ring-opening polymerization/nitroxide-mediated polymerization (ROP/NMP) combination. The hydrogel formation at around 30 °C was demonstrated to be mediated by intermicellar bridging through the PEG central block. Such result was particularly highlighted by the inability of PEG-PLA-PNIPAAm triblock analog of same composition to gelify. The hydrogels degraded through hydrolysis of PLA esters, until complete mass loss due to the diffusion of the recovered PEG and PNIPAAM/micelle based-residues in the solution. Interestingly, hydrophobic molecules such as riluzole (neurotrophic drug) or cyanine 5.5 (imaging probe) could be easily loaded in the hydrogels' micelle cores by mixing them with the copolymer solution at room temperature. Drug release was correlated to polymer mass loss. The hydrogels were shown to be cytocompatible (neuronal cells, in vitro) and injectable through small-gauge needle (in vivo in rats). Thus, this hydrogel platform displays highly attractive features for use in brain/soft tissue engineering as well as in drug delivery.
Synthesis of biocompatible nanocomposite hydrogels as a local drug delivery system
Colloid and Polymer Science, 2008
Nanocomposite biocompatible hydrogels (NCHG) were synthesised as model systems for in situ cured potentially local drug delivery devices for curing periodontal infections. The composite consists of the following components: nanoparticles (NPs), matrix gel, and chlorhexidine (CHX) as antibacterial drug. The NPs were obtained by free radical initiated copolymerization of the monomers, 2hydroxyethyl methacrylate (HEMA) and polyethyleneglycol dimethacrylate (PEGDMA), in aqueous solution. The same monomers were used to prepare crosslinked matrices by photopolymerization. NCHGs were obtained by mixing NPs, monomers, and drug in an aqueous solution then crosslinked by photopolymerization. Mechanical properties, swelling behavior, and the kinetics of drug release have been investigated. It was found that compression strength values increased with increasing ratio of the crosslinker PEGDMA. Incorporation of NPs into the matrix resulted similar compression strength as the matrix hydrogel. The hydrated NCHGs swelled more slowly but admitted more water. The drug was incorporated in NPs by swelling in CHX aqueous solution or added to the solution of monomer mixture followed by photopolymerization. Studies of release kinetics revealed that on average 60% of the loaded drug was released. The most rapid release was observed over a 24 h period for matrix gels with low crosslinking density. For NCHGs, the release period exceeded 48 h. An unexpected result was observed for NCHGs without drug in the NPs. In this case, increasing release was observed for the first 24 h. Thereafter, however, the apparent quantity of detectable drug decreased dramatically.
In situ injectable gelling systems have been extensively investigated with the aim of being applied for minimally invasive drug delivery or injectable tissue engineering. This article explores the injectable in-situ gelling system for prolonged release parenteral drug delivery system and their strategies of preparation. Here, we describe in situ-forming injectable hydrogel systems, prepared usinga variety of chemical cross linkers or physical interactions, for application in drug delivery. There are many newer approaches for in situ injectable hydrogels that can be delivered in minimally invasive techniques such as injection, ocular or nasal administration while protecting drugs or cells from the hostile environment. Recently, the Michael addition reaction between thiol and vinyl groups, the click reaction between bis (yne) molecules and multi arm azides, and the Schiff base reaction have been investigated for generation of injectable hydrogels, due to the high selectivity and biocompatibility of these reactions. Non-covalent physical interactions have also been proposed as cross linking mechanisms for in situ forming injectable hydrogels. Hydrophobic interactions, ionic interactions, stereo-complex formation, complementary pair formation, and host-guest interactions drive the formation of 3D polymeric networks. In particular, supramolecular hydrogels have been developed using the host-guest chemistry of cyclodextrin (CD), which allows highly selective, simple, and biocompatible cross linking. Finally, we review the current state of the art of injectable hydrogel systems for application in drug delivery, cell therapy and tissue regeneration.
Polymeric Biomaterial Based Hydrogels for Biomedical Applications
Journal of Biomaterials and Nanobiotechnology, 2011
The paper describes the synthesis of pH sensitive interpenetrating polymeric network (IPN) beads composed of chitosan, glycine, glutamic acid, cross linked with glutaraldehyde and their use for controlled drug release. The drug was loaded into beads by varying their composition such as, amount of crosslinker glutaraldehyde, ratio of chitosan, glycine and glutamic acid. The beads were characterized by fourier transform infrared (FTIR) spectroscopy to confirm the cross linking reaction and drug interaction with crosslinked polymer in beads, Scanning Electron Microscopy (SEM) to understand the surface morphology and Differential scanning calorimetry (DSC) to find out the thermal stability of beads. X-Ray Diffraction (XRD) investigation was carried out to determine the crystalline nature of drug after loading into chitosan-glycine-glutamic acid IPN beads. Results indicated amorphous dispersion of chlorpheniramine maleate (CPM) in the polymeric matrix. The swelling behavior of the beads at different time intervals was monitored in solutions of pH 2.0 and pH 7.4. The release experiments were performed in solutions of pH 2.0 and pH 7.4 at 37˚C using chlorpheniramine maleate (CPM) as a model drug. The swelling behavior and release of drug were observed to be dependent on pH, degree of cross linking and their composition. The results indicate that the cross linked IPN beads of chitosan-glycine-glutamic acid might be useful as a vehicle for controlled release of drug. The kinetics of drug release from beads was best fitted by Higuchi's model in which release rate is largely governed by rate of diffusion through the matrix.
Hydrogels in drug delivery: Progress and challenges
Polymer, 2008
There has been considerable progress in recent years in addressing the clinical and pharmacological limitations of hydrogels for drug delivery applications but substantial challenges remain. Here we discuss recent progress in overcoming these challenges, particularly with regards to effectively delivering hydrogels inside the body without implantation, prolonging the release kinetics of drugs from hydrogels, and expanding the nature of drugs which can be delivered using hydrogel-based approaches.
Commercial hydrogel product for drug delivery based on route of administration
Frontiers in chemistry, 2024
Hydrogels are hydrophilic, three-dimensional, cross-linked polymers that absorb significant amounts of biological fluids or water. Hydrogels possess several favorable properties, including flexibility, stimulus-responsiveness, versatility, and structural composition. They can be categorized according to their sources, synthesis route, response to stimulus, and application. Controlling the cross-link density matrix and the hydrogels' attraction to water while they're swelling makes it easy to change their porous structure, which makes them ideal for drug delivery. Hydrogel in drug delivery can be achieved by various routes involving injectable, oral, buccal, vaginal, ocular, and transdermal administration routes. The hydrogel market is expected to grow from its 2019 valuation of USD 22.1 billion to USD 31.4 billion by 2027. Commercial hydrogels are helpful for various drug delivery applications, such as transdermal patches with controlled release characteristics, stimuli-responsive hydrogels for oral administration, and localized delivery via parenteral means. Here, we are mainly focused on the commercial hydrogel products used for drug delivery based on the described route of administration.
Preparation of Nanocomposite Hydrogels and Its in vitro Release Behaviour on Captopril
Asian Journal of Chemistry, 2013
INTRODUCTION Hydrogels are three-dimensional networks of hydrophilic polymer chains, which can absorb and retain a large amount of water 1. The reasons of using nanoparticles in hydrogels for drug delivery result from their basic properties. Foremost is due to their small size, penetrate within even small capillaries and are taken up within cells, which allows for efficient drug accumulation at the targeted sites in the body 2-4. Use of biodegradable materials for nanoparticles preparation allows for sustained drug release within the target site over a period of days or even weeks after injection 5. Organic/inorganic nanocomposites (NCs) are functional materials consisting of immiscible organic and inorganic components and complex nanometer-scale structures can be fabricated there from. As a typical example, polymer/clay nanocomposites have been extensively studied and successfully developed for many applications 6. Haraguchi and Takehisa 7 reported the creation of a novel nanocomposite hydrogel with a unique organic-inorganic network structure by extending the concept of nanocomposite to the field of hydrogel materials. The nanocomposite hydrogels (NCHs) exhibited extraordinary mechanical, optical, swelling/deswelling properties which could simultaneously overcome the restrictions of conventional chemically crosslinked hydrogels. The formation of NCHs was achieved, not by the mere incorporation of clay nano-particles Nanocomposite hydrogels are interesting for biomedical applications due to their bio compatibility and good water sorption diffusion properties. The pH sensitive interpenetrating polymer network based nanocomposite hydrogels was prepared from montmorillonite nanoclays by free radical polymerization and solvent sorption method was used for drug loading. Drug used was captopril an angiotensin converting enzyme inhibitor. Interactions and thermal stabilities were studied using fourier transform infrared spectroscopy, differential scanning calorimerty, thermogravimetric analysis. The morphology of the nanocomposite hydrogels was characterized by scanning electron microscopy (SEM), swelling study and per cent drug loading reveals the formation of compatible nanocomposite hydrogels. In vitro drug release in the pH of 1.2 and 7.4 fitted with kinetic equation models. This shows that the swelling ratios of the nanocomposite hydrogels has been influenced by the pH of the external media and also increased with an increasing order of clay addition, Drug loading of the gels increased with an increasing concentration of captopril. The fabricated formulation shows targeted release of the drug in intestine (pH 7.4).