Controlled drug release from hydrogel nanoparticle networks (original) (raw)
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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.
Drug Delivery, 2006
The present work is focused on investigating the controlled drug release behavior of Poly [N-isopropylacrylamide-co-2-Hydroxyethylacrylate] (P [NIPAm-HEAc])-based hydrogel. The synthesis process includes the preparation of monodispersed hydrogel nanoparticles containing specific functional groups, followed by cross-linking to neighboring spheres to stabilize the entire network. The color and volume of these crystalline hydrogel networks can reversibly change in response to external stimuli such as temperature, pH, and other environmental conditions. The feasibility of the hydrogel as a controlled release vehicle for 5-fluorouracil is evaluated.
Macromolecular bioscience, 2017
A hybrid hydrogel composed of solid lipid nanoparticles (LNPs) entrapped within chemically cross-linked carboxymethylcellulose (CMC) is developed to achieve localized and sustained release of lipophilic drugs. The analysis of LNP stability as well as the hydrogel swelling and mechanical properties confirm the successful incorporation of particles up to a concentration of 50% w/wCMC . The initial LNP release rate can be prolonged by increasing the particle diameter from 50 to 120 nm, while the amount of long-term release can be adjusted by tailoring the particle surface charge or the cross-linking density of the polymer. After 30 d, 58% of 50 nm diameter negatively charged LNPs escape from the matrix while only 17% of positively charged nanoparticles are released from materials with intermediate cross-linking density. A mathematical diffusion model based on Fick's second law is efficient to predict the diffusion of the particles from the hydrogels.
Journal of Applied Polymer Science, 2012
Poly(N-isopropylacrylamide) (PNIPAM) hydrogels were simply prepared by free radical polymerization in different methanol-water mixture. A scanning electron microscopy study revealed that the freeze-dried hydrogels were macroporous. The swelling ratios in water at 20 C of the resulting hydrogels followed the order: X 0.43 >X 0.21 >X 0.76 % X 0.57 >X 0.31 >X 0.13 >X 0.06 >X 0 , where X m denotes a gel prepared in a methanol-water mixture with m mole fraction of methanol (x m ). Below the lower critical solution temperature, the swelling ratio values of all of the hydrogels gradually decreased with the increase in the temperature. The complete collapse of the PNIPAM chain of all the gels occurred at about 38 C, whereas the same was observed at about 35 C for the conventional gel prepared in water. The swelling ratio values of all the PNIPAM gels in the methanol-water mixtures with different x m values at 20 C passed through a minimum in the cononsolvency zone. The deswelling rates of the hydrogels decreased in the following order: X 0.43 > X 0.31 > X 0.21 > X 0.57 > X 0.76 % X 0.13 > X 0.06 > X 0 . The reswelling rates of these hydrogels decreased in the following order: X 0 > X 0.31 > X 0.06 % X 0.13 > X 0.76 > X 0.57 > X 0.21 > X 0.43 . The release rates of the Tramadol Hydrochloride drug at 37 C from the drug-loaded hydrogels were almost same for all of the hydrogels. V C 2012 Wiley Periodicals, Inc. J Appl Polym Sci
Journal of Polymer Research, 2017
Dual-responsive nanogels were prepared by polymerization of itaconic acid (IA) and copolymerization with methacrylic acid (MA) in aqueous solution of hydroxypropyl cellulose (HPC) and cross-linking with N, N′-methylenebisacrylamide (MBAm) through an easy and green process. FTIR spectroscopy, TEM, AFM, DLS and zeta potential studies confirmed the semiinterpenetrating (semi-IPN) polymer network structure of nanogels. The LCST of HPC was increased to a higher temperature than HPC's intrinsic LCST, while the presence of the MA comonomer improved the hydrophobicity of the copolymer and reduced LCST to about body temperature and suppressed the excessive nanogel aggregation. It was found that the concentration of reactants impacted the process of nanogel formation. Additionally, an increasing of cross-linker concentration led to a reduced size of HPC nanogels. Besides, the diameter of nanogels was changed with the temperature and pH. TEM and AFM photographs of copolymer nanogels illustrated that the nanoparticles with small diameters (<100 nm) were prepared. With loading the doxorubicin into the copolymer nanogels, the particle size became larger (about 150 nm) and due to the electrostatic interaction of the cationic drug with anionic particles, the zeta potential was increased. Drug release processes were followed at pH = 5.0 and 7.4 and with 37-and 41-°C temperatures, respectively. The maximum in-vitro release studies of drug-loaded nanogels, which is 91% for the pH 5.0 buffer solution at 41°C, demonstrated the temperature-and pH-sensitivity of prepared copolymer nanogels.
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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;smart&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; 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.
Journal of Sol-Gel Science and Technology, 2014
Supramolecular hydrogels (SMGel) have attracted much attention as a drug and gene delivery system in recent years. In this study, SMGels based on the triblock copolymer of poly-e-caprolactone-polyethylene glycol-poly-e-caprolactone (PCL-PEG-PCL) and acyclodextrin (a-CD) were prepared and evaluated for the delivery of two model drugs, naltrexone hydrochloride and vitamin B 12 . Tri-block copolymers were synthesized easily in 15 min by ring-opening polymerization using the microwave irradiation technique, and their structures were determined by gel permeation chromatography and nuclear magnetic resonance methods. SMGels composed of various concentrations of the copolymer and a-CD were prepared and characterized for their rheological behaviour, their gel formation time and in vitro drug release profile. The results indicated that copolymers with a PCL to PEG ratio of 1:4 are suitable for SMGel preparation. The most viscose system with good syringeability was prepared by mixing 12 % wt a-CD and 10 % wt of copolymer. The gelation was found to occur within a minute after mixing. The viscosity of the hydrogel systems was determined as a function of shear rate. Finally, in vitro B 12 release through the hydrogel systems was studied. Up to 80 % of Vitamin B 12 was released through this system during a period of 20 days. Rheological evaluation revealed that the hydrogel has shear thinning properties, and the system regained its ground rheological state in a time dependent manner. Polymer concentration did not affect the drug release profiles. Finally, it was concluded that such systems are appropriate drug delivery systems due to their ability to provide a controlled drug release profile and their shear thinning thixotropic behaviour, which makes them syringeable and injectable.
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.
European Journal of Pharmaceutics and Biopharmaceutics, 2009
This paper presents the development of new pH-sensitive, amphiphilic and biocompatible hydrogels based on alginate-g-PCL, cross-linked with calcium ions to form beads, prepared for controlled delivery of poorly water-soluble drug. We have focused our study on the effect of the length of PCL chains (530 and 1250 g mol À1 ). Swelling profiles obtained clearly indicated that these hydrogels swell slightly (10-14%) in a simulated gastric fluid (pH 1.2), and strongly (700-1300% before disintegration) in a simulated intestinal fluid (pH 6.8). In both media, rates of swelling were lower for beads based on amphiphilic derivatives than for alginate/Ca 2+ ones due to the hydrophobic PCL grafts, and decreased when hydrophobic character increased. A model drug, theophylline, was entrapped into these hydrogels and release studies were carried out. The drug was protected in acidic fluid (only 14-20% of release for alginate-g-PCL hydrogel against 35% of release for alginate hydrogel during 350 min). The drug is released completely in neutral fluid due to ion exchanges and disintegration of the hydrogel. PCL leads to decrease in the release kinetics in SIF (2 h for alginate-g-PCL/Ca 2+ beads against 1 h for alginate/Ca 2+ beads). It was demonstrated that the establishment of clusters inside beads by intramolecular interactions between PCL grafts of 530 g mol À1 in salt media allowed to retain the drug and to slow down its release considerably.
Role of Polymer Concentration and Crosslinking Density on Release Rates of Small Molecule Drugs
International Journal of Molecular Sciences
Over the past few years, researchers have demonstrated the use of hydrogels to design drug delivery platforms that offer a variety of benefits, including but not limited to longer circulation times, reduced drug degradation, and improved targeting. Furthermore, a variety of strategies have been explored to develop stimulus-responsive hydrogels to design smart drug delivery platforms that can release drugs to specific target areas and at predetermined rates. However, only a few studies have focused on exploring how innate hydrogel properties can be optimized and modulated to tailor drug dosage and release rates. Here, we investigated the individual and combined roles of polymer concentration and crosslinking density (controlled using both chemical and nanoparticle-mediated physical crosslinking) on drug delivery rates. These experiments indicated a strong correlation between the aforementioned hydrogel properties and drug release rates. Importantly, they also revealed the existence o...