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We report here a novel method for the synthesis of a pH-responsive composite using visible light. Formation of the pH-responsive layer is based on poly(methacrylic acid- g -ethylene glycol) as the macromer, eosin Y as the photoinitiator and triethanolamine as the co-initiator. The hydrogel was functionalized with hydrophobic domains through incorporation of crosslinked styrene–butadiene–styrene (SBS) copolymer into the pH-responsive prepolymer. Swelling ratios were decreased with the addition of SBS, and resulted in high hydrogel crosslink density. The composite allowed for controlled release of an anticonvulsant model drug, pregabalin, under neutral pH condition and the release was analyzed to describe the mode of transport through the network. In vitro human fibroblast survival assay and in vivo rabbit implantation experiments demonstrated that this hybrid network is not toxic and has desirable biocompatibility properties. This is the first report about the synthesis of a pH-responsive network incorporating crosslinked SBS synthesized under visible light. The approach for multifunctional membranes could allow the incorporation of molecules with specific functionalities so that sequential molecule delivery in response to specific stimuli could be achieved. [ABSTRACT FROM AUTHOR]

Hydrogels designed to sustainably release bioactive molecules are extensively used to enhance tissue repair and regenerative therapies. Along this line, numerous efforts are made to control the molecular release rate and amount. In contrast, few efforts are made to control the molecular release pattern, and, subsequently, modulate the spatial organization of newly forming tissues, including blood vessels. Therefore, using a hydrogel printed to release vascular endothelial growth factor (VEGF) into a pre-defined pattern, this study demonstrates that spatial distribution of VEGF is important in guiding growth direction of new blood vessels, and also in retaining the structural integrity of pre-existing vasculature. Guided by a computational model, we fabricated a patch composed of micro-sized VEGF-releasing poly(ethylene glycol) diacrylate (PEGDA) hydrogel cylinders using an ink-jet printer. Interestingly, hydrogel printed with computationally optimized spacing created anisotropically aligned vasculature exclusively when the printed gel pattern was placed parallel to pre-existing blood vessels. In contrast, vascular sprouting from placing the printed gel pattern perpendicular to pre-existing vessels resulted in deformation and structural disintegration of the original vasculature. We envision that this study will be useful to better understand angiogenesis-modulated neovascularization and further improve the treatment quality for various wounds and tissue defects. [ABSTRACT FROM AUTHOR]

Despite the recent expansion of peptide drugs, delivery remains a challenge due to poor localization and rapid clearance. Therefore, a hydrogel-based platform technology was developed to control and sustain peptide drug release via matrix metalloproteinase (MMP) activity. Specifically, hydrogels were composed of poly(ethylene glycol) and peptide drugs flanked by MMP substrates and terminal cysteine residues as crosslinkers. First, peptide drug bioactivity was investigated in expected released forms (e.g., with MMP substrate residues) in vitro prior to incorporation into hydrogels. Three peptides (Qk (from Vascular Endothelial Growth Factor), SPARC 113 , and SPARC 118 (from Secreted Protein Acidic and Rich in Cysteine)) retained bioactivity and were used as hydrogel crosslinkers in full MMP degradable forms. Upon treatment with MMP2, hydrogels containing Qk, SPARC 113 , and SPARC 118 degraded in 6.7, 6, and 1 days, and released 5, 8, and, 19% of peptide, respectively. Further investigation revealed peptide drug size controlled hydrogel swelling and degradation rate, while hydrophobicity impacted peptide release. Additionally, Qk, SPARC 113 , and SPARC 118 releasing hydrogels increased endothelial cell tube formation 3.1, 1.7, and 2.8-fold, respectively. While pro-angiogenic peptides were the focus of this study, the design parameters detailed allow for adaptation of hydrogels to control peptide release for a variety of therapeutic applications. [ABSTRACT FROM AUTHOR]

Environmentally sensitive hydrogels as one of the most potential drug delivery systems have gained considerable interest in recent years. In the present study, we synthesized a newly temperature-responsive composite hydrogel based on attapulgite (ATP) and poly (N-isopropylacrylamide) (PNIPAM) as the localized drug carriers for drug delivery. The as-prepared ATP/PNIPAM hydrogel has large aperture which significantly improved the quantity of adsorption of drugs, exhibiting the excellent properties of drug release. The scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD) were used to characterize the ATP/PNIPAM. The swelling/deswelling behaviors and the release of ciprofloxacin lactate were studied. When the temperature was below the low critical solution temperature (LCST), the swelling property of hydrogels was excellent and the swelling rate was large. And, the drug release rate increased with the increase of the content of attapulgite in the composite hydrogel when it was put in the buffer solution (pH 7.38) at 37.0 °C. Therefore, the composite hydrogels might be very useful for its application in biomedical fields. [ABSTRACT FROM AUTHOR]

We have developed a series of pH- and temperature-stimuli-sensitive vinyl hydrogels, bearing α-amino acid residues ( l -phenylalanine, l -valine) and incorporating magnetic nanoparticles of different chemical compositions (CoFe 2 O 4 and Fe 3 O 4 ). The goal was to study the potential applications of these nanocomposites in the controlled release of doxorubicin (DOXO), a potent anticancer drug. The strength of the electrostatic interaction between the protonated nitrogen of the DOXO molecule and the ionized carboxylic groups of the hydrogel allowed effective control of the drug release rate in saline solutions. The embedded magnetic nanoparticles were an additional remote control of the drug release under the stimulus of an appropriate external alternating magnetic field (AMF). Data showed that the controlled release of DOXO proceeded for months and followed a diffusion-controlled release mechanism, while maintaining the amount of released drug within acceptable therapeutic windows. The amount of the released DOXO was found in all cases substantially higher than the “control” because the application of the AMF augments in stimulating the nanoparticles within the DOXO-loaded hydrogel. In vitro experiments have shown that the released DOXO is able to induce cell death to cervix adenocarcinoma cells (HeLa cells). [ABSTRACT FROM AUTHOR]

Thermo switchable magnetic hydrogels undoubtedly have a great potential for medical applications since they can behave as smart carriers able to transport bioactive molecules to a chosen part of the body and release them on demand via magneto-thermal activation. We report on the ability to modify the lower critical solution temperature (LCST) of poly( N-isopropylacrylamide) (PNIPAM) on demand from 32 °C to LCST ≥37 °C. This was achieved by the absorption of controlled amounts of magnetite nanoparticles on the polymer chains. We show, through the effect on cell viability, that the resulting magnetic PNIPAM is able to trap and to release bio-active molecules, such as cell growth factors. The activities of the released bio molecule are tested on human umbilical vein endothelial cells culture. We demonstrate that the LCST of the magnetic PNIPAM can be reached remotely via inductive heating with an alternating magnetic field. This approach on magnetic PNIPAM clearly supports appealing applications in safe biomedicine. [ABSTRACT FROM AUTHOR]

Since the early days of the Journal of Controlled Release , there has been considerable interest in materials that can release drug on an “on-demand” basis. So called “stimuli-responsive” and “intelligent” systems have been designed to deliver drug at various times or at various sites in the body, according to a stimulus that is either endogenous or externally applied. In the past three decades, research along these lines has taken numerous directions, and each new generation of investigators has discovered new physicochemical principles and chemical schemes by which the release properties of materials can be altered. No single review could possibly do justice to all of these approaches. In this article, some general observations are made, and a partial history of the field is presented. Both open loop and closed loop systems are discussed. Special emphasis is placed on stimuli-responsive hydrogels, and on systems that can respond repeatedly. It is argued that the most success at present and in the foreseeable future is with systems in which biosensing and actuation (i.e. drug delivery) are separated, with a human and/or cybernetic operator linking the two. [ABSTRACT FROM AUTHOR]

Over the past decades, significant progress has been made in the field of hydrogels as functional biomaterials. Biomedical application of hydrogels was initially hindered by the toxicity of crosslinking agents and limitations of hydrogel formation under physiological conditions. Emerging knowledge in polymer chemistry and increased understanding of biological processes resulted in the design of versatile materials and minimally invasive therapies. Hydrogel matrices comprise a wide range of natural and synthetic polymers held together by a variety of physical or chemical crosslinks. With their capacity to embed pharmaceutical agents in their hydrophilic crosslinked network, hydrogels form promising materials for controlled drug release and tissue engineering. Despite all their beneficial properties, there are still several challenges to overcome for clinical translation. In this review, we provide a historical overview of the developments in hydrogel research from simple networks to smart materials. [ABSTRACT FROM AUTHOR]

Multifunctional injectable thermo-/pH-responsivehydrogels as releasesystems for the oral delivery of small molecule drugs and the localdelivery of protein are presented. The injectable interpenetratingpolymer network (IPN) hydrogels based on poly(ethylene glycol) methacrylate, N-isopropylacrylamide, and methacrylated alginate were preparedby using ammonium persulfate (APS) and N,N,N′,N′-tetramethylethylenediamine(TEMED) as a redox initiator system at body temperature, and the obtainedhydrogels overcame the instability of calcium cross-linked alginatehydrogels under physiological conditions. The hydrogels showed goodmechanical strength by rheometer and exhibited temperature and pHsensitivity by a swelling test. Diclofenac sodium (DCS) as a modelfor small molecule water-soluble anti-inflammatory drugs and bovineserum albumin (BSA) as a model for protein drugs were encapsulated in situin the hydrogel. The DCS and BSA release resultsindicated that these hydrogels, as carriers, have great potentialfor use in the oral delivery of small molecule drugs and for long-termlocalized protein release. Furthermore, the cytotoxicity of thesehydrogels was studied via live/dead viability and alamarBlue assaysusing adipose tissue-derived mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we investigated the in vitro and in vivo properties and performance of a celecoxib-loaded hydrogel based on a fully acetyl-capped PCLA-PEG-PCLA triblock copolymer. Blends of different compositions of celocoxib, a drug used for pain management in osteoarthritis, and the acetyl-capped PCLA-PEG-PCLA triblock copolymer were mixed with buffer to yield temperature-responsive gelling systems. These systems containing up to 50 mg celecoxib/g gel, were sols at room temperature and converted into immobile gels at 37 °C. In vitro, release of celecoxib started after a ∼10-day lag phase followed by a sustained release of ∼90 days. The release was proven to be mediated by polymer dissolution from the gels. In vivo (subcutaneous injection in rats) experiments showed an initial celecoxib release of ∼30% during the first 3 days followed by a sustained release of celecoxib for 4–8 weeks. The absence of a lag phase and the faster release seen in vivo were likely due to the enhanced celecoxib solubility in biological fluids and active degradation of the gel by macrophages. Finally, intra-articular biocompatibility of the 50 mg/g celecoxib-loaded gel was demonstrated using μCT-scanning and histology, where no cartilage or bone changes were observed following injection into the knee joints of healthy rats. In conclusion, this study shows that celecoxib-loaded acetyl-capped PCLA-PEG-PCLA hydrogels form a safe drug delivery platform for sustained intra-articular release. [Copyright &y& Elsevier]

Herein, C 16 alkyl chain- grafted -xanthan copolymer was synthesized and characterized. The copolymer self-assembled into nanometer-size spherical micellar structures in water and incorporated ∼100% glibenclamide into its deeper lipophilic confines. The micellar dispersion exhibited negative zeta potential value (−27.6 mV). The copolymer micelles controlled the drug release rate in phosphate buffer solution (pH 6.8) for an extended period. Further incorporation of drug-loaded copolymer micelles into O -carboxymethyl xanthan hydrogel particles slowed the drug release rate in HCl solution (pH 1.2) as well as in phosphate-buffered solution (pH 6.8) (releasing only ∼8% drug in 2 h). The drug release data correlated well with the degree of swelling of the hydrogel particles in different drug release media. Scanning electron microscopy revealed spherical shape of the hydrogel particles (600 μm). X-ray diffraction and Fourier transform infrared (FTIR) spectroscopy analyses suggested amorphous encapsulation of the drug and its chemical compatibility with the polymers, respectively. Pharmacodynamic evaluation suggested that the formulations had an immense potential in controlling blood glucose level in animal model over a longer duration. In summary, it was pointed out that the copolymer micelles of glibenclamide, a poor water-soluble anti-diabetic, and their subsequent entrapment into hydrogel particles could be a promising approach in the controlled and effective management of diabetes. [ABSTRACT FROM AUTHOR]

In vitro drug release testing is an appropriate approach to identify critical parameters helping to predict drug release from drug-eluting stents (DES) prior to studying drug release behavior under in vivo conditions. Drug release and distribution from DES coated with a fluorescent model substance were studied in vitro using the vessel-simulating flow-through cell equipped with different long-term stable hydrogel compartments composed of agarose, polyacrylamide or poly(vinyl alcohol). The obtained experimental results were compared with the results of finite-element modeling obtained using experimentally determined diffusion coefficients and partition coefficients. In spite of differences regarding these parameters, experimental and mathematical data yielded only minor differences between the different gels regarding the release and distribution behavior and reasonable agreement between the modeling and the experiment was obtained. In an attempt to further elucidate the dosage form behavior, the diffusion coefficients in the gel as well as in the stent coating were systematically varied in the finite-element model. Changes in the diffusivity in the stent coating mainly impacted on the initial concentrations. Slower diffusion inside the hydrogel yielded a retarded elution from the stent coating and a higher model substance accumulation in the gel compartment at late time points. [ABSTRACT FROM AUTHOR]

Abstract: Infection after artificial joint replacement is a serious problem, which requires the re-implantation of prosthesis. To aim at developing bone filling materials having both osteoconductivity and ability as a sustained drug release carrier, composites of wool keratin or carboxymethylated (CM) keratin hydrogels with hydroxyapatite were prepared and evaluated as a sustained drug release carrier. CM-keratin was prepared by the reaction of keratin extracted from wool with iodoacetic acid. Hydrogels were obtained by dropping keratin or CM-keratin solution into CaCl2 solution. The composites were obtained by immersing hydrogels in simulated body fluid (SBF). The introduction of carboxymethyl groups to keratin facilitated the deposition of hydroxyapatite on hydrogel. After 7days of immersion in SBF, a 4–5 times higher amount of hydroxyapatite was accumulated on CM-keratin hydrogel than that on keratin hydrogel. When salicylic acid was loaded on keratin and CM-keratin hydrogels, a good sustained release was observed; that is, 90% of a drug was released up to 14days after 60 and 45% of the initial burst in 1day. On the other hand, initial release within 1day was suppressed by forming a composite with hydroxyapatite and the release was almost ceased at 3days when 60% of the drug was released. Although further improvement to prolong drug release might be necessary, CaKHA and CaCMKHA are expected to be a promising novel type of bone filling materials which has both osteoconductivity and sustained drug release ability. [Copyright &y& Elsevier]

The objective of this study is to design biodegradable hydrogels for the controlled release of deferoxiamine (DFO) and evaluate their biological activity. When the DFO was added to human umbilical vein endothelial cells cultured in 5.0% O2, the level of hypoxia-inducible factor-1α and vascular endothelial growth factor significantly increased compared with that without DFO. The expression of angiogenesis-related genes was accordingly increased by the DFO addition. An aqueous solution of mixed gelatin and DFO was freeze-dried, and dehydrothermally treated at 140°C for 24h to prepare a gelatin hydrogel incorporating DFO. In the release test with phosphate-buffered saline solution (PBS) at 37°C, an initial DFO release of 60% was observed, followed by no release. When placed in PBS containing collagenase, the hydrogel was enzymatically degraded with time, and consequently released DFO in a degradation-dependent manner. After the hydrogel incorporating DFO was injected intramuscularly into a mouse model of hind limb ischemia, the number of new blood vessels formed was significantly higher than that with free DFO and DFO-free hydrogel. It is concluded that the DFO-containing hydrogel shows promising for inducing angiogenesis locally. [ABSTRACT FROM AUTHOR]

Thermosensitive hydrogels developed for buccal delivery of salbutamol were prepared using poloxamer analogs (Kolliphor® P407/P188), xanthan gum (Satiaxane® UCX930) and NaCl. P188 increased gelation temperature (T sol–gel) by 2.5–5°C, micellization temperature (<1°C) and gelation time by >3s. To obtain a suitable T sol–gel at 28–34°C, P407 and P188 concentrations were set to 18–19% and 1%. NaCl reduced T sol–gel (>2°C) out of the optimal range. Six formulations containing 0.05–0.1% Satiaxane® fulfilled the temperature criteria. Concerning the gel strength, 1% P188 had no significant effect, NaCl increased it at 20°C, and Satiaxane® enhanced it at 20°C and 37°C. The release study using membrane-less (to mimic oral cavity) and membrane (to mimic buccal mucosa side) methods allowed a complete investigation showing that erosion and diffusion both contributed to the drug release but differed according to the formulation. In the membraneless method, simple P407 formulations had weak ability to retain salbutamol (T 80 =35min). P188 accelerated drug release. NaCl accelerated release in the membraneless method by 5–11min but slightly reduced it in the membrane method. The hydrogels containing Satiaxane® exhibited the slowest release. In the membrane method, combination of P407/P188/Satiaxane® provided a sustained diffusion with a burst effect (T 25 =9.6min, T 80 =97.8min), which provides potential clinical interests. [ABSTRACT FROM AUTHOR]

Abstract: The anticancer drug cisplatin was encapsulated within the cucurbit[7]uril macrocycle to form the host-guest complex: cisplatin@CB[7]. This was then incorporated into gelatin and 0–4% w/v polyvinyl alcohol (PVA)-based hydrogels as slow release drug delivery vehicles. The hydrogels demonstrated predicable swelling and disintegration dependent on the PVA concentration. The hydrogel with the highest PVA content was slower to swell and release drug compared with lower concentrations of PVA. The effect of the hydrogel PVA concentration on in vitro cytotoxicity was examined using A2780/CP70 ovarian cancer cells. Over the 24h drug exposure time used, hydrogels containing 4% PVA showed a 20% decrease in viable cells compared to the control, whereas hydrogels containing 0% and 2% PVA induced an 80% and 45% inhibition of cell growth, respectively. There was no measurable difference in the in vitro cytotoxicity of free cisplatin and cisplatin@CB[7] containing hydrogels. Finally, the in vivo effectiveness of a 2%-PVA hydrogel implanted under the skin of nude mice bearing A2780/CP70 xenografts showed that low dose hydrogels containing cisplatin@CB[7] (30μg equivalent of drug) was just as effective as an intraperitoneal high dose administration of free cisplatin (150μg) at inhibiting tumour growth. [Copyright &y& Elsevier]

The objective of the present study was to develop 2-hydroxypropyl methacrylate-co-polyethylene methacrylate [p(HPMA-co-PEG-MEMA)] hydrogels that are able to efficiently entrap doxorubicin for the application of loco-regional control of the cancer disease. Systemic chemotherapy provides low clinical benefit while localized chemotherapy might provide a therapeutic advantage. In this study, effects of hydrogel properties such as PEG chains length, cross-linking density, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. In addition, the characterization of the hydrogel formulations was conducted with swelling experiments, permeability tests, Fourier transform infrared, SEM, and contact angle studies. In these drug-hydrogel systems, doxorubicin contains amine group that can be expected a strong Lewis acid-base interaction between drug and polar groups of PEG chains, thus the drug was released in a timely fashion with an electrostatic interaction mechanism. It was observed that doxoaibicin release from the hydrogel formulations decreased when the density of cross-linking, and drug/polymer ratio were increased while an increase in the PEG chains length of the macro-monomer (i.e. PEG-MEMA) in the hydrogel system was associated with an increase in water content and doxorubicin release. The biocompatibility of the hydrogel formulations has been investigated using two measures: cytotoxicity test (using lactate dehydrogenase assay) and major serum proteins adsorption studies. Antitumor activity of the released doxorubicin was assessed using a human SNU398 human hepatocellular carcinoma cell line. It was observed that doxorubicin released from all of our hydrogel formulations which remained biologically active and had the capability to kill the tested cancer cells. [ABSTRACT FROM AUTHOR]

In this paper, with W/O Pickering emulsion stabilized by modified SiO2 nanoparticles as template, PVA/SiO2 composite microspheres with PVA hydrogel cores and shells of SiO2 nanoparticles are successfully fabricated through freezing/thawing method. The final structure and constituents of the products are investigated through SEM, FT1R, and TGA. The PVA/SiO2 composite microspheres obtained are applied as a drug carrier to study their controlled release behaviors and methylene blue is used as a model drug. The effect of PVA concentration, SiO2 nanoparticle concentration, and freezing/ thawing cycles on the morphology of products and release behaviors is studied. All release curves are, respectively, fitted by Monoexponential equation, Higuchi equation, Weibull equation, and Hixson-Crowell equation. Weibull equation is found to give the best fit to the release process. The fitted results prove that the drug release from the PVA/SiO2 composite microspheres follows Fick diffusion. [ABSTRACT FROM AUTHOR]

Abstract: The penetration behavior into human nails and animal hoof membranes of a novel antifungal agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established. [Copyright &y& Elsevier]

Abstract: In this paper, a lipid material glycerol monooleate was used as the starting material to synthesize the oxidized glycerol monooleate (OGMO). OGMO was subsequently linked to chitosan (CS) via imine bonds ( C N ) to obtain a new chitosan-based polymer (OGMO-CS), which can form hydrogels rapidly in aqueous media. Scanning electron microscopy, swelling behavior studies and degradation kinetics studies were performed to demonstrate the effect of this synthetic modification on the hydrogels formation of chitosan network and in vitro drug release. The effects of OGMO-CS type, dry hydrogels percentage, release media and drug loading on the sustained release of the model drug trimetazidine hydrochloride were evaluated. The release profiles of the hydrogels could be described by the Peppas–Sahlin mechanism, a combination of Fickian diffusion and Case-II relaxation. Based on the fact that numerous pharmaceutical lipids are available, the present study may pave the way for other lipids to be employed as modifiers of chitosan for more innovative chitosan derivatives with versatile properties and pharmaceutical applications. [Copyright &y& Elsevier]

Injectable hydrogels have attracted a lot of attention in drug delivery, however, their capacity to deliver water-insoluble or hydrophobic anti-cancer drugs is limited. Here, we developed injectable graphene oxide/graphene composite supramolecular hydrogels to deliver anti-cancer drugs. Pluronic F-127 was used to stabilize graphene oxide (GO) and reduced graphene oxide (RGO) in solution, which was mixed with α-cyclodextrin (α-CD) solution to form hydrogels. Native hydrogel was used as control. GO or RGO slightly shortened gelation time. The storage and loss moduli of the hydrogels were tracked by dynamic force measurement. The storage modulus of GO or RGO composite hydrogels was larger than that of the native hydrogel. Hydrogels were unstable in solution and eroded gradually. GO or RGO in Pluronic F-127 solution could potentially improve the solubility of the water-insoluble anti-cancer drug camptothecin (CPT), especially with large drug-loaded CPT amount. Drug release behaviors from solutions and hydrogels were characterized. The nanocomponents (GO or RGO) were able to bind more drug molecules either for CPT or for doxorubicin hydrochloride (DXR) in solution. Therefore, GO or RGO composite hydrogel could potentially enable better controlled and gentler drug release (for both CPT and DXR) than native hydrogel. [ABSTRACT FROM PUBLISHER]

The purpose of this study is to develop novel triazole-containing hydrogels (TGs) as drug carrier and to investigate the sustained drug release accomplished by their time-dependent swelling behavior. The synthetic pathway of TGs includes: (1) DCC-coupling on hydroxyethyl methacrylate (HEMA) to prepare HEMA-alkyne (HA), (2) click-coupling to prepare a triazole-ring-containing monomer (TM), and (3) the synthesis of a series of TGs. The aggregation between triazole rings is found to be responsible for drug release controllability. Rhodamine 6G is studied as a model anticancer drug for release experiments. The effects of pH and temperature on the properties of sustained drug release are also studied. [ABSTRACT FROM AUTHOR]

This research described a novel composite electrospun nanofibers, which were consisted of MPEG-b-PLA micelles, chitosan, and PEO, realizing controlled release of both hydrophobic and hydrophilic drugs. 5-FU and Cefradine used as model drugs were successfully loaded in the nanofibers. The in vitro studies showed there was a low initial burst release of 5-FU from micelles-loaded nanofibers, and the final release proportion was about 91.4% after continually releasing for 109h. In vitro cytotoxicity studies revealed that 5-FU-loaded nanofibers restrained HepG-2 cells efficiently, and the cell viability was 45.9% after three days of cultivation in solutions containing micelles-loaded nanofibers with 21.6 μg 5-FU. All results suggested that micelles-loaded nanofibers with two kinds of drugs can be used as an effective controlled drug delivery vehicle and may have a bright future in cancer chemotherapy or clinical treatments. [ABSTRACT FROM AUTHOR]

Thermosensitive hydrogels based on chitosan are of great interests for injectable implant drug delivery. The poly(ethylene glycol)-grafted-chitosan (PEG-g-CS) hydrogel was reported as a potential thermosensitive system. The objective of the present study is to evaluate the cytotoxicity, in vivo degradation and drug release of PEG-g-CS hydrogel. Cytotoxicity was evaluated using L929 murine fibrosarcoma cell line. Degradation and drug release in vivo were investigated by subcutaneous injection of the hydrogel into Sprague-Dawley rats. PEG-g-CS polymer exhibits no significant cytotoxicity when its concentration is less than 3 mg mL"1. After being implanted, PEG-g-CS hydrogel maintains its integrity for two weeks and collapses, merging into the tissue, in the third week. It causes moderate inflammatory response but no fibrous encapsulation around the hydrogel is found. The hydrogel presents a three-week sustained release of cyclosporine A with no significant burst release in vitro and produces the effective drug concentration in blood for more than five weeks in vivo, performing almost the same bioavailability to chitosan/glycerophosphate hydrogel. Further modifications of PEG-g-CS hydrogel might be necessary to modulate the degradation and to mitigate the fluctuations in blood drug concentration. [ABSTRACT FROM AUTHOR]

A new synthetic tripeptide-basedhydrogel has been discovered atphysiological pH and temperature. This hydrogel has been thoroughlycharacterized using different techniques including field emissionscanning electron microscopic (FE-SEM) and high-resolution transmissionelectron microscopic (HR-TEM) imaging, small- and wide-angle X-raydiffraction analyses, FT-IR, circular dichroism, and rheometric analyses.Moreover, this gel exhibits thixotropy and injectability. This hydrogelhas been used for entrapment and sustained release of an antibioticvancomycin and vitamin B12at physiological pH and temperaturefor about 2 days. Interestingly, MTT assay of these gelator moleculesshows almost 100% cell viability of this peptide gelator, indicatingits noncytotoxicity. [ABSTRACT FROM AUTHOR]

Abstract: Microemulsions (MEs) have been studied extensively as colloidal carriers for the delivery of both water-soluble and lipid-soluble drugs. Our previous study showed that addition of water to ME formulations resulted in phase transition to either liquid crystal (LC) or coarse emulsion (CE). The aim of this study was to investigate whether these MEs could be used as drug delivery vehicles for prolonged release through in-situ phase transition following extravascular injection. Three ME formulations from the same pseudo-ternary phase diagram were investigated with respect to their phase transition behavior, and in-vivo drug release; a coarse emulsion-forming ME (CE-ME), an oil rich LC-forming ME (LC-ME1), and an oil poor LC-forming ME (LC-ME2). CE-ME was a W/O ME and both LC-MEs were O/W type. The release profiles of 99mTc labeled MEs following subcutaneous (SC) injection in rabbits were investigated with gamma-scintigraphy. The CE-ME dispersed readily in water, forming a CE, whereas the LC-forming MEs formed ‘depots’ in water. Polarized microscopy revealed a LC boundary spontaneously formed at the water/ME interface for the LC-MEs with the LC-ME2 forming a substantially thicker LC layer. The CE resulting from the water-induced transition of the CE-forming ME had a higher viscosity than the MEs, but lower than the LCs resulted from LC-MEs. Compared to LC-ME1, LC-ME2 underwent more rapid phase transition and the resultant LC had significant higher viscosity. The LCs formed from both ME formulations exhibited pseudoplastic properties; increasing the shear rate decreased the apparent viscosity exponentially. Following SC injection into the animal thigh, the LC-MEs had more prolonged release of 99mTc in a first-order manner, than CE-ME. The oil poor LC-ME2 had the slowest release with a t1/2 of 77min, 2.3 times longer than the oil rich LC-ME1; consistent with the thickness of LC layer formation observed in-vitro and their relative viscosities. In conclusion, the present in-vivo study has demonstrated the application of MEs as extravascular injectable drug delivery systems for sustained release. The retention of the vehicles at the injection site and the release rate were determined predominantly by their phase transition rather than ME type or oil content. [Copyright &y& Elsevier]

As a sustained-release drug depot for localized cancer treatment, in situ thermo-sensitive hydrogel has attracted increasing interests. However, it is currently a big challenge to achieve high drug-loading, sustained and stable drug release, as well as long-term local drug retention simultaneously. We hypothesized that this goal could be accomplished by incorporating the nanocrystals (NCs) of a hydrophobic drug, such as paclitaxel (PTX) into the thermo-sensitive hydrogel (Gel). Hence, a PTX-NCs-Gel system has been constructed with thermo-sensitive Pluronic F127, using PTX-NCs and Taxol® as the controls. Besides, near infra-red agent DiR was used to prepare PTX/DiR hybrid NCs and PTX/DiR hybrid NCs-Gel as well. As a result, this hydrogel system could achieve a high drug loading of PTX up to 3mg/ml while stabilize the particle size of PTX-NCs significantly compared with PTX-NCs alone. There was no obvious interaction between PTX-NCs and F127. Obviously, PTX/DiR hybrid NCs-Gel presented better localized retention capacity and a much longer retention time in murine 4T1 tumor than PTX/DiR hybrid NCs and Cremophor/ethanol solubilized DiR in vivo. With a linear elimination, over 10% of PTX still remained inside of mouse 4T1 tumor 20days after intratumoral dosing of PTX-NCs-Gel. Importantly, PTX-NCs exhibited comparable cytotoxity against 4T1 and MCF-7 cells in vitro compared with Taxol®, which could ensure the efficacy of PTX-NCs-Gel. After intratumoral injection, PTX-NCs-Gel was found to be the most effective among all PTX formulations in the 4T1 and MCF-7 tumor-bearing mice models, with much lower system toxicity than Taxol®. In general, it is believed that the novel thermo-sensitive hydrogel system prepared in this study with PTX-NCs affords high drug-loading, sustained and stable drug release, as well as extended drug retention inside of tumor, which results in better therapy and lower toxicity. [ABSTRACT FROM AUTHOR]

Abstract: Temperature has been extensively explored as a trigger to control the delivery of a payload from environment-sensitive polymers. The need for an external heat source only allows limited spatiotemporal control over the delivery process. We propose a new approach by using the dissipative properties of a hydrogel matrix as an internal heat source when the material is mechanically loaded. The system is comprised of a highly dissipative hydrogel matrix and thermo-sensitive nanoparticles that shrink upon an increase in temperature. Exposing the hydrogel to a cyclic mechanical loading for a period of 5 min leads to an increase of temperature of the nanoparticles. The concomitant decrease in the volume of the nanoparticles increases the permeability of the hydrogel network facilitating the release of its payload. As a proof-of-concept, we showed that the payload of the hydrogel is released after 5–8 min following the initiation of the mechanical loading. This delivery method would be particularly suited for the release of growth factor as it has been shown that cell receptor to growth factor is activated 5–20 min following a mechanical loading. [Copyright &y& Elsevier]

Highlights: [•] We used graphene oxide as a drug-binding effector for cancer therapy drug loading and release. [•] The possible mechanism of the gelation of graphene oxide and polysaccharide was discussed. [•] Graphene oxide composite hydrogels showed excellent pH sensitive. [•] The KGM/SA/GO-3 hydrogels could control the drug release well. [Copyright &y& Elsevier]

Drug-coated balloons are medical devices designed to locally deliver drug to diseased segments of the vessel wall. For these dosage forms, drug transfer to the vessel wall needs to be examined in detail, since drug released into the blood is cleared from the site. In order to examine drug transfer, a new in vitro setup was developed combining the estimation of drug loss during advancement to the site of application in a model coronary artery pathway with a hydrogel compartment representing, as a very simplified model, the vessel wall. The transfer of fluorescent model substances as well as the drug paclitaxel from coated balloons to the simulated vessel wall was evaluated using this method. The model was suitable to quantify the fractions transferred to the hydrogel and also to qualitatively assess distribution patterns in the hydrogel film. In the case of fluorescein sodium, rhodamin b and paclitaxel, vast amounts of the coated substance were lost during the simulated passage and only very small fractions of about 1% of the total load were transferred to the gel. This must be attributed to good water solubility of the fluorescent substances and the mechanical instability of the paclitaxel coating. Transfer of the hydrophobic model substance triamterene was however nearly unaffected by the preliminary tracking procedure with transferred fractions ranging from 8% to 14%. Analysis of model substance distribution yielded inhomogeneous distributions indicating that the coating was not evenly distributed on the balloon surface and that a great fraction of the coating liquid did not penetrate the folds of the balloon. This finding is contradictory to the generally accepted assumption of a drug depot inside the folds and emphasizes the necessity to thoroughly characterize in vitro performance of drug-coated balloons to support the very promising clinical data. [ABSTRACT FROM AUTHOR]

Abstract: This study evaluated the in vitro and in vivo performance of antibiotic-releasing porous polymethylmethacrylate (PMMA)-based space maintainers comprising a gelatin hydrogel porogen and a poly(d l-lactic-co-glycolic acid) (PLGA) particulate carrier for antibiotic delivery. Colistin was released in vitro from either gelatin or PLGA microparticle loaded PMMA constructs, with gelatin-loaded constructs releasing colistin over approximately 7days and PLGA microparticle-loaded constructs releasing colistin for up to 8weeks. Three formulations with either burst release or extended release at different doses were tested in a rabbit mandibular defect inoculated with Acinetobacter baumannii (2×107 colony forming unitsml−1). In addition, one material control that released antibiotic but was not inoculated with A. baumannii was tested. A. baumannii was not detectable in any animal after 12weeks on culture of the defect, saliva, or blood. Defects with high dose extended release implants had greater soft tissue healing compared with defects with burst release implants, with 8 of 10 animals showing healed mucosae compared with 2 of 10 respectively. Extended release of locally delivered colistin via a PLGA microparticle carrier improved soft tissue healing compared with implants with burst release of colistin from a gelatin carrier. [Copyright &y& Elsevier]

Abstract: Many vitamins, bioactive lipids and over 40% of newly developed drugs are hydrophobic, and their poor water solubility limits their delivery using conventional formulations. In this work we investigated a composite gel system formulated from microemulsions embedded in alginate hydrogels, and showed that it is capable of loading several hydrophobic compounds with a wide range of aqueous solubility. All gels were clear, with no precipitations, indicating the solubility of the drugs in the gels. The release behavior was similar for different microemulsion formulations, various drugs and increasing concentrations of a drug. These findings indicate that our system could potentially act as a generic system, where the properties of the release do not depend on the drug but rather on the attributes of the gel. The structure of composite gels was investigated using small-angle scattering of X-rays and neutrons (SAXS and SANS, respectively). SANS showed more sensitivity to the structure of the microemulsion in the composite gel than SAXS did. SAXS and SANS plots of the composite gels show that both the droplets and the gel network preserve their structure when mixed together. [Copyright &y& Elsevier]

Abstract: To study the release of liposome-associated drugs into hydrogels, we designed and synthesized two pH-sensitive rhodamine derivatives to use as model compounds of different lipophilicities. The dyes were fluorescent when in the free form released from liposomes into the chitosan hydrogel, but not when incorporated within liposomes. The effect of liposomal composition, surface charge and vesicle size on the release of those incorporated dyes was evaluated. The lipophilicity of the rhodamine derivatives affected both the amount and rate of release. While liposome size had only a minor effect on the release of dyes into the hydrogel, the surface charge affected the release to a greater extent. By optimizing the characteristics of liposomes we could develop a liposomes-in-hydrogel system for application in wound therapy. We further characterized liposomes-in-hydrogel for their rheological properties, textures and moisture handling, as well as their potential to achieve a controlled release of the dye. The polymer-dependent changes in the hydrogel properties were observed upon addition of liposomes. The charged liposomes exhibited stronger effects on the textures of the chitosan hydrogels than the neutral ones. In respect to the ability of the system to handle wound exudates, chitosan-based hydrogels were found to be superior to Carbopol-based hydrogels. [Copyright &y& Elsevier]

Interpenetrating polymer network hydrogel beads of pectin and sodium carboxymethyl xanthan were prepared by ionotropic gelation with Al-3 ions and covalent cross-linking with glutaraldehyde for sustained delivery of diltiazem hydrochloride. Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning colorimetry and scanning electron microscopy were used to characterise the hydrogel beads. The swelling of the hydrogel and the release of drug were relatively low in pH 1.2 buffer solutions. However, higher swelling and drug release were observed in pH 6.8 buffer solutions. The carboxyl functional groups of hydrogels undergo ionisation and the osmotic pressure inside the beads increases resulting in higher swelling and drug release in higher pH. The release of drug depends on concentration of polymer, amount and exposure time of cross-linker and drug content in the hydrogel matrices. The present study indicated that the hydrogel beads minimised the drug release in pH 1.2 buffer solutions and to prolong the drug release in pH 6.8 buffer solutions. [ABSTRACT FROM AUTHOR]

Abstract: Highly porous nanocellulose aerogels prepared by freeze-drying from various nanofibrillar cellulose (NFC) hydrogels are introduced as nanoparticle reservoirs for oral drug delivery systems. Here we show that beclomethasone dipropionate (BDP) nanoparticles coated with amphiphilic hydrophobin proteins can be well integrated into the NFC aerogels. NFCs from four different origins are introduced and compared to microcrystalline cellulose (MCC). The nanocellulose aerogel scaffolds made from red pepper (RC) and MCC release the drug immediately, while bacterial cellulose (BC), quince seed (QC) and TEMPO-oxidized birch cellulose-based (TC) aerogels show sustained drug release. Since the release of the drug is controlled by the structure and interactions between the nanoparticles and the cellulose matrix, modulation of the matrix formers enable a control of the drug release rate. These nanocomposite structures can be very useful in many pharmaceutical nanoparticle applications and open up new possibilities as carriers for controlled drug delivery. [Copyright &y& Elsevier]

Highlights: [•] A biodegradable and non-toxic polysaccharides cross-linked hydrogels was developed. [•] Avastin loaded hydrogel for ocular drug delivery. [•] Avastin was sustained release from hydrogel with well structure stability. [Copyright &y& Elsevier]

Highlights: [•] Ultrasonication is applied for preparation of nano-sized indomethacin particles. [•] Encapsulation with polysaccharides is used to protect particles from aggregation. [•] Controlled release of indomethacin is realized by increasing pH in the solution. [Copyright &y& Elsevier]

Abstract: Biodegradable oligo(poly(ethylene glycol) fumarate) (OPF) composite hydrogels have been investigated for the delivery of growth factors (GFs) with the aid of gelatin microparticles (GMPs) and stem cell populations for osteochondral tissue regeneration. In this study, a bilayered OPF composite hydrogel that mimics the distinctive hierarchical structure of native osteochondral tissue was utilized to investigate the effect of transforming growth factor-β3 (TGF-β3) with varying release kinetics and/or insulin-like growth factor-1 (IGF-1) on osteochondral tissue regeneration in a rabbit full-thickness osteochondral defect model. The four groups investigated included (i) a blank control (no GFs), (ii) GMP-loaded IGF-1 alone, (iii) GMP-loaded IGF-1 and gel-loaded TGF-β3, and (iv) GMP-loaded IGF-1 and GMP-loaded TGF-β3 in OPF composite hydrogels. The results of an in vitro release study demonstrated that TGF-β3 release kinetics could be modulated by the GF incorporation method. At 12weeks post-implantation, the quality of tissue repair in both chondral and subchondral layers was analyzed based on quantitative histological scoring. All groups incorporating GFs resulted in a significant improvement in cartilage morphology compared to the control. Single delivery of IGF-1 showed higher scores in subchondral bone morphology as well as chondrocyte and glycosaminoglycan amount in adjacent cartilage tissue when compared to a dual delivery of IGF-1 and TGF-β3, independent of the TGF-β3 release kinetics. The results suggest that although the dual delivery of TGF-β3 and IGF-1 may not synergistically enhance the quality of engineered tissue, the delivery of IGF-1 alone from bilayered composite hydrogels positively affects osteochondral tissue repair and holds promise for osteochondral tissue engineering applications. [Copyright &y& Elsevier]

Abstract: Implants that simultaneously function as an osteoconductive matrix and as a device for local drug or growth factor delivery could provide an attractive system for bone regeneration. In our previous work, we prepared hollow hydroxyapatite (abbreviated HA) microspheres with a high surface area and mesoporous shell wall and studied the release of a model protein, bovine serum albumin (BSA), from the microspheres into phosphate-buffered saline (PBS). The present work is an extension of our previous work to study the release of BSA from similar HA microspheres into a biocompatible hydrogel, poly(ethylene glycol) (PEG). BSA-loaded HA microspheres were placed in a PEG solution which was rapidly gelled using ultraviolet radiation. The BSA release rate into the PEG hydrogel, measured using a spectrophotometric method, was slower than into PBS, and it was dependent on the initial BSA loading and on the microstructure of the microsphere shell wall. A total of 35–40% of the BSA initially loaded into the microspheres was released into PEG over ~14days. The results indicate that these hollow HA microspheres have promising potential as an osteoconductive device for local drug or growth factor delivery in bone regeneration and in the treatment of bone diseases. [Copyright &y& Elsevier]

Nowadays solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been investigated as carrier systems for many applications. SLNs consist of pure solid lipids, while NLCs are made of a solid matrix that entraps liquid lipid nano-compartments. These systems revealed several advantages compared to other colloidal carrier systems. They provide a controlled drug release and an increase in chemical stability of the incorporated drugs. Moreover, they are safe carriers which can be produced easily in a large scale. This paper reviews the commonly used materials, production techniques, characterization, and physical stability of these systems. [ABSTRACT FROM AUTHOR]

Thermosensitive hydrogels were prepared by free radical polymerization of N-isopropylacrylamide (NIPAM) and 2-acrylamido-2-methylpropanesulphonic acid (AMPS) in presence of polyethylene glycol (PEG) as macroinitiator. The incorporation of functional monomer in the hydrogel was confirmed by infrared spectroscopy. The equilibrium swelling ratio (ESR), deswelling rate, volume transition temperature, and surface morphology of synthesized hydrogels are found to be dependent on concentration of AMPS monomer in the feed composition. The equilibrium swelling ratio (ESR) and water retention properties increase with increasing AMPS concentration in hydrogels and decrease with increasing salt concentration in external medium. The hydrogel with high dose of AMPS has high loading efficiency of theophylline drug, whereas the in-vitro release of the drug is delayed for a prolonged period in swollen gels above LCST of PNIPAM. [ABSTRACT FROM PUBLISHER]

Abstract: Hydrogels are presently under investigation as matrices for the controlled release of bioactive molecules, in particular pharmaceutical proteins, and for the encapsulation of living cells. For these applications, it is often required that the gels degrade under physiological conditions. This means that the originally three-dimensional structure has to disintegrate preferably in harmless products to ensure a good biocompatibility of the hydrogel. In this overview, different chemical and physical crosslinking methods used for the design of biodegradable hydrogels are summarized and discussed. Chemical crosslinking is a highly versatile method to create hydrogels with good mechanical stability. However, the crosslinking agents used are often toxic compounds, which have been extracted from the gels before they can be applied. Moreover, crosslinking agents can give unwanted reactions with the bioactive substances present in the hydrogel matrix. Such adverse effects are avoided with the use of physically crosslinked gels. [Copyright &y& Elsevier]

Abstract: Environmentally sensitive hydrogels have enormous potential in various applications. Some environmental variables, such as low pH and elevated temperatures, are found in the body. For this reason, either pH-sensitive and/or temperature-sensitive hydrogels can be used for site-specific controlled drug delivery. Hydrogels that are responsive to specific molecules, such as glucose or antigens, can be used as biosensors as well as drug delivery systems. Light-sensitive, pressure-responsive and electro-sensitive hydrogels also have the potential to be used in drug delivery and bioseparation. While the concepts of these environment-sensitive hydrogels are sound, the practical applications require significant improvements in the hydrogel properties. The most significant weakness of all these external stimuli-sensitive hydrogels is that their response time is too slow. Thus, fast-acting hydrogels are necessary, and the easiest way of achieving that goal is to make thinner and smaller hydrogels. This usually makes the hydrogel systems too fragile and they do not have mechanical strength necessary in many applications. Environmentally sensitive hydrogels for drug delivery applications also require biocompatibility. Synthesis of new polymers and crosslinkers with more biocompatibility and better biodegradability would be essential for successful applications. Development of environmentally sensitive hydrogels with such properties is a formidable challenge. If the achievements of the past can be extrapolated into the future, however, it is highly likely that responsive hydrogels with a wide array of desirable properties can be made. [Copyright &y& Elsevier]

In this study, to clarify the utility of polypseudorotaxane (PPRX) hydrogels composed of poly(ethylene glycol) (PEG) and α- or γ-cyclodextrin (α- or γ-CyD) as a sustained-release system for protein drugs, we prepared CyD PPRX hydrogels including lysozyme, and then the release profiles of lysozyme from these hydrogels and the release mechanisms were investigated. The α- and γ-CyD formed PPRX hydrogels by threading onto one PEG chain and two PEG chains, respectively. The formation of α- and γ-CyD PPRX hydrogels including lysozyme was based on physical cross-linking arisen from their columnar structures. The in vitro release rates of lysozyme were markedly decreased by the encapsulation into CyD PPRX hydrogels. In addition, when release data were plotted according to Korsmeyer-Peppas model, the exponent values ( n) in the α- and γ-CyD systems had no statistically significant difference, suggesting that these release mechanisms were almost same. In conclusion, these results suggest that α- and γ-CyD PPRX hydrogels possess the potential as a sustained-release system for lysozyme. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2891-2899, 2012 [ABSTRACT FROM AUTHOR]

Abstract: Sodium alginate (SA) grafted with polyglycidyl methacrylate hydrogels (PGMA-g-SA) was prepared as pH sensitive drug delivery matrices for riboflavin (RF). The hydrogel copolymer matrices were compared with calcium alginate (CA) beads for swelling, degradation, entrapment efficiency and in vitro release of RF. The structure, surface morphology of the CA beads and the prepared hydrogels as well as the chemical stability of the encapsulated drug were characterized by FT-IR and SEM, respectively. The results demonstrate that the optimal formulation was achieved with PGMA-g-SA proportion of (0.75mol/1g) and loaded RF 0.03g. It has been observed that the in vitro release study of RF from this formulation was superior to the other ones and was able to maintain the release for ∼3 and 4 days for the simulated intestinal fluid (SIF) and simulated gastric fluid (SGF), respectively. In general, it has been shown that, GMA grafted onto SA enhanced drug entrapment efficiency, decreased swelling and degradation behaviors of the carrier. In addition, it slowed and controlled the release of RF from the PGMA-g-SA hydrogel compared with pure SA beads crosslinked with Ca2+ ions alone, which thereby provides a facile and effective method to improve the drug delivery systems. [Copyright &y& Elsevier]

Abstract: A model system, α-chymotrypsin (Cht) (a protease) and a cleavable peptide-chromogen (pro-drug) covalently incorporated into a hydrogel, was investigated to understand the mechanisms of covalent loading and release by enzymatic cleavage in bio-responsive delivery systems. Using EDC and Sulfo-NHS, terminal carboxyl groups of N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide, a cleavable chromogen, were conjugated to primary amines of a hydrated poly(HEMA)-based hydrogel. Hydrogel disks were incubated in buffered Cht causing enzyme-mediated cleavage of the peptide and concomitant release of the chromophore for monitoring. To investigate substrate loading and the effects of hydrogel morphology on the system, the concentration of the amino groups (5, 10, 20, and 30mol%) and the cross-linked density (1, 5, 7, 9 and 12mol%) were independently varied. Loading–Release Efficiency of the chromogen was shown to exhibit a positive relation to increasing amino groups (AEMA). The release rates demonstrated a negative relation to increasing cross-linked density attributed to decreasing void fractions and increasing tortuosities. The diffusion coefficient of Cht, D0,Cht, was determined to be 6.9±0.5×10−7 cm2 s−1, and the range of Deff of Cht for 1 to 12mol% TEGDA was determined to be 6.9×10−8 to 0.1×10−8 cm2 s−1. We show how these parameters may be optimized and used to achieve programmed release rates in engineered bio-responsive systems. [Copyright &y& Elsevier]

Abstract: A local drug delivery system based on sustained drug release is an attractive approach to treat brain tumors. We have developed a novel device using drug-incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in thermoreversible gelation polymer (TGP) formulation (drug/PLGA/TGP formulation). TGP forms a gel at body temperature but sol at room temperature. Therefore, when this formulation is injected into the brain tumor, the PLGA microspheres in TGP gel are localized at the injection site and do not diffuse throughout the brain tissue; eventually, sustained drug release from PLGA microspheres is achieved at the target site. In this study, two chemotherapeutic drugs (camptothecin (CPT) or vincristine (VCR)) were incorporated into PLGA microspheres to prepare drug/PLGA/TGP formulations. VCR/PLGA microspheres exhibited the higher encapsulation efficiency than CPT/PLGA microspheres (70.1% versus 30.1%). In addition, VCR/PLGA microspheres showed a higher sustained release profile than CPT/PLGA microspheres (54.5% versus 72.5% release, at 28 days). Therapeutic effect (mean survival) was evaluated in the C6 rat glioma model (control group, 18 days; CPT/PLGA/TGP treatment group, 24 days; VCR/PLGA/TGP treatment group, 33 days). In particular, the VCR/PLGA/TGP formulation produced long-term survivors (>60 days). Therefore, this formulation can be therapeutically effective formulation for the glioma therapy. [Copyright &y& Elsevier]

Abstract: Charge groups in polyelectrolyte gels can affect the entrapment and release of ionic drugs as well as influencing the stability of colloidal and nanoparticulate drug delivery systems. An accurate knowledge of gel charge properties is therefore important to the understanding and design of such drug delivery systems. Existing rotating disk method for quantifying the surface potential of flat surfaces is based on the classical electrokinetic model that neglects the effect of surface conductivity and is therefore only applicable to ion-impenetrable hard surfaces. This classical electrokinetic model would be inaccurate for polyelectrolyte gel systems involving ion-penetrable charged layers or “soft” surfaces. In this study, we developed a new rotating disk model for characterizing charge properties of ion penetrable soft surfaces and tested it on polyvinyl alcohol (PVA)/polyacrylic acid (PAA), gelatin, and gelatin/PAA polyelectrolyte gels. In addition to classical electrokinetic parameters, the contribution of surface conductivity known to be very significant for soft and ion-penetrable gel surfaces has been taken into account in this new rotating disk model. Based on this new approach, two rotating gel disks of different radius but with identical gel composition and preparation procedures were employed for determining the gel surface potential and density of fixed charge groups. A comparison of the resulting data with that obtained from existing rotating disk model ignoring the surface conductivity reveals a significant underestimation of the gel surface potential and the density of fixed charge groups by the ion-impenetrable hard surface approach. Our results thus confirm that the contribution of surface conductivity is significant in the electrokinetic characterization of polyelectrolyte gels that can be evaluated with our new rotating disk model. [Copyright &y& Elsevier]

Abstract: There is a clear need for methods to provide a safe controlled release of therapeutic proteins, either to achieve and maintain high local protein concentrations, or for sustained systemic delivery. We have developed a protein delivery system that combines in situ cross-linkable polysaccharide hydrogels with gelatin. This formulation is injectable, easy to apply, and obviates the need for organic solvents or potentially toxic cross-linking agents in the formulation process. The cross-linked polysaccharides themselves (comprising hyaluronic acid, dextran and/or carboxymethylcellulose) provided prolonged release of fluorescently labeled albumin (FITC-albumin). The duration of release was markedly extended by the incorporation of gelatin into the formulation: FITC-albumin and interleukin-2 (IL-2) were released over the course of more than 3weeks. The IL-2 maintained >70% activity throughout that time. Gelatin also accelerated the gelation time of the hydrogels, and reduced their swelling in phosphate-buffered saline. The composite hydrogel (dextran–carboxymethylcellulose–gelatin) showed minimal cytotoxicity in vitro, and benign tissue reaction after subcutaneous injection in rats. [Copyright &y& Elsevier]

Abstract: The multifactorial pathological progress of spinal cord injury (SCI) is probably the main reason behind the absence of efficient therapeutic approaches. Hence, very recent highlights suggest the use of new multidrug delivery systems capable of local controlled release of therapeutic agents. In this work, a biocompatible hydrogel-based system was developed as multiple drug delivery tool, specifically designed for SCI repair strategies. Multiple release profiles were achieved by loading gel with a combination of low and high steric hindrance molecules. In vitro, in vivo and ex vivo release studies showed an independent combination of fast diffusion-controlled kinetics for smaller molecules together with slow diffusion-controlled kinetics for bigger ones. A preserved functionality of loaded substances was always achieved, confirming the absence of any chemical stable interactions between gel matrix and loaded molecules. Moreover, the relevant effect of the cerebrospinal fluid flux dynamics on the drug diffusion in the spinal cord tissue was here revealed for the first time: an oriented delivery of the released molecules in the spinal cord tract caudally to the gel site is demonstrated, thus suggesting a more efficient gel positioning rostrally to the lesion. [Copyright &y& Elsevier]