Tuning drug release from smart microgel–hydrogel composites via cross-linking (original) (raw)
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Pharmaceutics
In this study, poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate) hydrogels were synthesized using free radical initiated copolymerization method. Four hydrogels with different cross-linker concentrations were prepared. Semi-crystalline, cross-linked copolymer networks were confirmed by FTIR, SEM and XRD analysis. Variation of swelling behaviour was monitored gravimetrically and thermo-responsiveness has been noticed. An application of synthesized thermo-responsive hydrogels as carriers for the modulated release of anti-inflammatory model drug was investigated. Moreover, naproxen loading into these hydrogels was also determined using FTIR, SEM and XRD techniques and release was analyzed using HPLC method at simulated physiological conditions. Swelling kinetic and mechanism of water transport, as well as diffusion of naproxen through the hydrogels were analyzed. Thus, the aim of this work was to study various compositions of obtained hydrogels and their possibility of applic...
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.
Controlled drug release from hydrogel nanoparticle networks
Journal of Controlled Release, 2004
Monodisperse nanoparticles of poly-N-isopropylacrylamide-co-allylamine (PNIPAM-co-allylamine) and PNIPAM-coacrylic acid (PNIPAM-co-AA) were synthesized. The close-packed PNIPAM-co-allylamine and PNIPAM-co-AA nanoparticles were converted to three-dimensional gel networks by covalently crosslinking neighboring particles at room temperature and neutral pH using glutaric dialdehyde and adipic acid dihydrazide, respectively. Controlled release studies were conducted using dextran markers of various molecular weights as model macromolecular drugs. Release was quantified under various physical conditions, including a range of temperatures and dextran molecular weights. Dextran, entrapped in cavities in the nanoparticle network, was released with a rate regulated by their molecular weights and cavity size. No release from a conventional bulk PNIPAM gel, with high crosslinking density, was observed. The rate of release from the PNIPAM-co-allylamine network was temperature-dependant, being much faster at room temperature than that at human body temperature. In contrast, release of low molecular weight dextrans from the PNIPAM-co-AA network showed a temperature-independent release profile. These nanoparticle networks have several advantages over conventional bulk gels for controlling the release of high molecular weight biomolecules. D
Polymers for Advanced Technologies, 2004
N-Isopropylacrylamide/itaconic acid copolymeric hydrogels were prepared by irradiation of the ternary mixtures of N-isopropylacrylamide/itaconic acid/water by c-rays at ambient temperature. The dependence of swelling properties and phase transitions on the comonomer concentration and temperature were investigated. The hydrogels showed both temperature and pH responses. The effect of comonomer concentration on the uptake and release behavior of the hydrogels was studied. Methylene blue (MB) was used as a model drug for the investigation of drug uptake and release behavior of the hydrogels. The release studies showed that the basic parameters affecting the drug release behavior of the hydrogels were pH and temperature of the solution.
Journal of Applied Polymer Science, 2011
Stimuli-sensitive drug delivery systems (DDSs) have attracted considerable attention in medical and pharmaceutical fields; thermo-sensitive DDS dealing with poly(N-isopropylacrylamide) (PNIPAM) have been widely studied. Hydrogels composed of temperature-sensitive NIPAM and biocompatible and pH-sensitive maleic acid (MAc) were synthesized by sedimentation polymerization. Experiments on drug release from the crosslinked NIPAM-co-MAc hydrogel loaded with ibuprofen into different pH buffer solutions were successfully carried out at temperature swing between 25 and 40 C. The in vitro release studies have showed that the release rate depended on acidity or basicity (polarity) of the medium and the gel and swelling ratio of the gel network as a function of the environmental pH and temperature. The SEM image of the dry bead gave more insight into the surface architecture and the thermal studies shine light on the decomposition pattern and glass transition temperature of the gel. The mechanism of the drug release was discussed in relation to the diffusion rate and the abrupt change in the pH of the medium. V
Journal of Materials Science, 2013
This study highlights the advantages of functionalized poly(N-isopropylacrylamide) (PNIPAAm) microgels over pure PNIPAAm microgels in terms of polymer network properties and drug release profiles. PNIPAAm network was modified by addition of maleic anhydride (MA) as a comonomer and by formation of interpenetrating polymer network in the presence of alginate. The functionalized thermosensitive microgels in the size range from 20 to 80 lm and with better performance in comparison with pure PNIPAAm microgels were prepared by inverse suspension polymerization. The impact of MA and alginate on the PNIPAAm microgel structure was evaluated through analysis of microgel size, size distribution, volume phase transition temperature (VPTT), equilibrium swelling ratio as well as morphology of the system. It was shown that the controlled modification of PNIPAAm network could result in microgels of considerably improved swelling capacity with unchanged thermosensitivity and maintained open pore morphology. In addition, drug release behavior of microgels could be markedly altered. Release of procaine hydrochloride from the selected microgels was studied using Franz diffusion cell at temperatures below and above VPTT of the microgels. Temperature-controlled drug release pattern was dependent on the type of functionalization of PNIPAAm network. According to drug loading properties and drug release mechanism, PNIPAAm/MA copolymer microgels demonstrated the optimal performances.
Journal of Polymer Science Part A: Polymer Chemistry, 2018
A facile synthetic strategy was developed for the preparation of thermoresponsive nanocomposite hydrogels comprising crosslinked chitosan (CS) networks and poly(N-isopropylacrylamide) [p(NIPAAm)] nanogels. First, thermoresponsive p(NIPAAm) nanogels were synthesized via emulsion polymerization. The p(NIPAAm) nanogels were introduced into methacrylamide CS (MC) solution and the free-radical initiated crosslinking reaction of MC produced nanogel-embedded hydrogels. The last step involves the loading of the antibacterial model drug levofloxacin (LFX) into the prepared nanocomposite hydrogels by allowing the preformed hydrogels to swell to equilibrium in the drug's aqueous solution. The integration of p(NIPAAm) nanogel into CS networks facilitates thermoresponsive release of LFX with an enhancement of the drug-loading capacity within the hydrogel. Notably, thermoresponsive drug-release was achieved without unwarranted modification of the hydrogel's dimension and shape, although an increase in temperature caused the collapse of the p(NIPAAm) nanogels. The thermoresponsive property of the investigated nanocomposite hydrogel is beneficial and may offer broad opportunities for drug temperature-triggered release for clinical applications. V
Journal of Polymer Research, 2014
Thermoresponsive colloidal microgels were prepared by precipitation copolymerization of N-isopropylacrylamide (NIPAM) and N-hydroxyethylacrylamide (HEAM) with various concentrations of a cross-linker in the presence of an anionic surfactant, sodium dodecylsulphate (SDS). The volume phase transition temperature (VPTT) of the prepared microgels was studied by dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-vis) and proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy. In addition, atomic force microscopy (AFM) was used to characterize the polydispersity and morphology of the microgels. Results indicated that poly(NIPAMco-HEAM) microgels are spherical and monodisperse. VPTTs of microgels determined by DLS and UV-vis methods are almost the same and very close to the human body temperature, presenting the microgels as candidates for biomedical application. The temperature at which the phase transition occurred is nearly independent of the cross-linking density, whereas the transition range is deeply influenced by temperature. Also, the SDS concentration was increased to decrease the average hydrodynamic size of the microgels, due to the electrostatic repulsion between the charged particles during the polymerization process. 1 H-NMR spectra of the microgels show a decrease in peak intensity with an increased temperature due to a reduction in molecular mobility of the polymer segments. Release rates of propranolol from microgels are deeply influenced by temperature; below the VPTT at 25°C, the drug is rapidly released at a rate comparable to that of a free drug, whereas above the VPTT (37 and 42°C), a fraction of the drug is mechanically expulsed in the first five min, followed by a prolonged release.