Viscoelastic analysis of single-component and composite PEG and alginate hydrogels

Hydrogels, three-dimensional hydrophilic polymer networks, are appealing candidate materials for studying the cellular microenvironment as their substantial water content helps to better mimic soft tissue. However, hydrogels can lack mechanical stiffness, strength, and toughness. Composite hydrogel systems have been shown to improve upon mechanical properties compared to their singlecomponent counterparts. Poly (ethylene glycol) dimethacrylate (PEGDMA) and alginate are polymers that have been used to form hydrogels for biological applications. Singlecomponent and composite PEGDMA and alginate systems were fabricated with a range of total polymer concentrations. Bulk gels were mechanically characterized using spherical indentation testing and a viscoelastic analysis framework. An increase in shear modulus with increasing polymer concentration was demonstrated for all systems. Alginate hydrogels were shown to have a smaller viscoelastic ratio than the PEGDMA gels, indicating more extensive relaxation over time. Composite alginate and PEGDMA hydrogels exhibited a combination of the mechanical properties of the constituents, as well as a qualitative increase in toughness. Additionally, multiple hydrogel systems were produced that had similar shear moduli, but different viscoelastic behaviors. Accurate measurement of the mechanical properties of hydrogels is necessary in order to determine what parameters are key in modeling the cellular microenvironment. © 2014 The Chinese Society of Theoretical and Applied Mechanics; Institute of Mechanics, Chinese Academy of Sciences and Springer-Verlag Berlin Heidelberg.

Preparation of uniform calcium alginate gel beads by membrane emulsification coupled with internal gelation

With the objective of making calcium alginate gel beads with small and uniform size, membrane emulsification coupled with internal gelation was proposed. Spherical gel beads with mean size of about 50 mum, and even smaller ones in water, and with narrow size distribution were successfully obtained. Experimental studies focusing mainly on the effect of process parameters on bead properties were performed. The size of the beads was mainly dependent on the diameter of the membrane pores. High transmembrane pressure made for large gel beads with wide size distribution. Low sodium alginate concentration produced nonspherical beads, whereas a high concentration was unsuitable for the production of small beads with narrow distribution. Thus 1.5% w/v was enough. A high surfactant concentration favored the formation of small beads, but the adverse effect on mass transfer should be considered in this novel process. (C) 2002 Wiley Periodicals, Inc.

Microspheres and microcapsules, a survey of manufacturing techniques: Part III: Solvent evaporation

A methodological survey of microsphere formation and microencapsulation techniques based on solvent extraction/evaporation techniques is presented. Thus, basic features of solvent extraction and solvent evaporation processes, including droplet formation, droplet/particle stabilization, and solvent removal, are outlined. Preparation of a wide range of microspherical and microcapsular products based on biodegradable polyesters, polysaccharides, and nonbiodegradable polymers are discussed. Dependence of microcapsule characteristics on manufacturing parameters, as well as performance evaluation of microspherical and microcapsular products, are also briefly covered.

Preparation and application of single polyelectrolyte microcapsules possessing tunable autofluorescent properties

Autofluorescent single polyelectrolyte microcapsules, exemplified by poly-L-lysine (PLL), have been prepared through glutaraldehyde-mediated covalent layer-by-layer (LbL) assembly and subsequent core removal. CaCO3 microparticles were used as template cores for the LbL deposition and removed by treatment of ethylenediamine tetraacetic acid disodium salt (EDTA). The prepared microcapsules, without conjugating an exterior fluorochrome, exhibited evenly distributed fluorescence.

Hollow DNA/PLL microcapsules with tunable degradation property as efficient dual drug delivery vehicles by alpha-chymotrypsin degradation

Hollow deoxyribonucleic acid (DNA)/poly-L-lysine (PLL) capsules were successfully fabricated through a layer-by-layer (LbL) self-assembly of DNA and PLL on porous CaCO3 microparticles, followed by removal of templates with ethylenediamine tetraacetic acid disodium salt (EDTA). The enzymatic degradation of the capsules in the presence of alpha-chymotrypsin was explored. The higher the enzyme concentration, the higher is the degradation rate of hollow capsules. in addition, glutaric dialdehyde (GA) cross-linking was found to be another way to manipulate degradation rate of hollow capsules.

A facile pathway to prepare enzymatically degradable microcapsules with tunable capsule shell properties

Dextran sulfate (DS)/poly-L-lysine (PLL) microcapsules are fabricated by an in situ coacervation method using DS-doped CaCO3 microparticles as templates. Twinned superstructures or spherical CaCO3 microparticles are produced depending on DS concentration in the starting Solution. DS/PLL microcapsules with ellipsoidal or spherical outline are obtained after removal of templates in disodium ethylene diamine tetraacetate dehydrate (EDTA) without PLL. Their shell thickness and negative surface charges increase with the DS weight percentage in the templates. The surface potential of DS/PLL microcapsules.

Cytotoxicity of liver targeted drug-loaded alginate nanoparticles

In this study, novel liver targeted doxorubicin (DOX) loaded alginate (ALG) nanoparticles were prepared by CaCl2 crosslinking method. Glycyrrhetinic acid (GA, a liver targeted molecule) modified alginate (GA-ALG) was synthesized in a heterogeneous system, and the structure of GA-ALG and the substitution degree of GA were analyzed by H-1 NMR, FT-IR and elemental analysis. The drug release profile under the simulated physiological condition and cytotoxicity experiments of drug-loaded GA-ALG nanoparticles were carried out in vitro. Transmission electron micrographs (TEM) and dynamic light scattering (DLS) analysis showed that drug-loaded GA-ALG nanoparticles have spherical shape structure with the mean hydrodynamic diameter around 214 +/- 11 nm.

Development of an in vitro multicellular tumor spheroid model using microencapsulation and its application in anticancer drug screening and testing

In this study, an in vitro multicellular tumor spheroid model was developed using microencapsulation, and the feasibility of using the microencapsulated. multicellular tumor spheroid (MMTS) to test the effect of chemotherapeutic drugs was investigated. Human MCF-7 breast cancer cells were encapsulated in alginate-poly-L-lysine-alginate (APA) microcapsules, and a single multicellular spheroid 150 mu m in diameter was formed in the microcapsule after 5 days of cultivation. The cell morphology, proliferation, and viability of the MMTS were characterized using phase contrast microscopy, BrdU-Iabeling, MTT stain, calcein AM/ED-2 stain, and H&E stain. It demonstrated that the MMTS was viable and that the proliferating cells were mainly localized to the periphery of the cell spheroid and the apoptotic cells were in the core. The MCF-7 MMTS was treated with mitomycin C (MC) at a concentration of 0.1, 1, or 10 times that of peak plasma concentration (ppc) for up to 72 h. The cytotoxicity was demonstrated. clearly by the reduction in cell spheroid size and the decrease in cell viability. The MMTS was further used to screen the anticancer effect of chemotherapeutic drugs, treated with MC, adriamycin (ADM) and 5-fluorouracil (5-FU) at concentrations of 0.1, 1, and 10 ppc for 24, 48, and 72 h. MCF-7 monolayer culture was used as control. Similar to monolayer culture, the cell viability of MMTS was reduced after treatment with anticancer drugs. However, the inhibition rate of cell viability in MMTS was much lower than that in monolayer culture. The MMTS was more resistant to anticancer drugs than monolayer culture. The inhibition rates of cell viability were 68.1%, 45.1%, and 46.8% in MMTS and 95.1%, 86.8%, and 91.6% in monolayer culture treated with MC, ADM, and 5-FU at 10 ppc for 72 h, respectively. MC showed the strongest cytotoxicity in both MMTS and monolayer, followed by 5-FU and ADM. It demonstrated that the MMTS has the potential to be a rapid and valid in vitro model to screen chemotherapeutic drugs with a feature to mimic in vivo three-dimensional (3-D) cell growth pattern.

A new cellular model for in vitro biocompatibility evaluation of microcapsule materials

Fibrosis caused by the host response to long-term transplanted microcapsules and the limitation of traditional L929 cell model for biocompatibility testing inspire the development of an assay of biocompatibility based on macrophage behavior. In this paper, the human monocytic cell line THP-1 was utilized for biocompatibility evaluation of microcapsule materials. The cell viability and secretion of nitric oxide (NO) and cytokines served as index of biocompatibility were assayed. It was found that the evaluated microcapsule materials had no effect on the stimulation of NO and cytokines secretion, which meant that these materials were biocompatible. Furthermore, it suggests the THP-1 cell a convenient in vitro experimental model that might be useful for long-term predictions of material biocompatibility.

Insight into permeability of protein through microcapsule membranes

The objective of this paper is to analyze the characteristics of protein permeability in alainate-polylysine-alginate (APA) and alginate-chitosan-alginate (ACA) microcapsules by mathematical models based on the balance of chemical potential. The comparison between calculated results and experimental data shows that the models can describe the process of protein diffusion from microcapsule and protein release into microcapsule successfully. The influences of membrane composition on the permeability of ACA microcapsule have been investigated and analyzed. The effect of resistance on the mass transfer is further analyzed theoretically with the aid of mathematical modeling. (c) 2005 Elsevier B.V. All rights reserved.

Zeolite-Loaded Alginate-Chitosan Hydrogel Beads as a Topical Hemostat

Hemorrhage is the leading cause of preventable death after a traumatic injury. Commercial hemostatic agents exist, but have various disadvantages including high cost, short shelf-lives, or secondary tissue damage. Polymer hydrogels provide a promising platform for the use of both biological and mechanical mechanisms to accelerate natural hemostasis and control hemorrhage. The goal of this work was to develop hydrogel particles composed of chitosan and alginate and loaded with zeolite in order to stop blood loss by targeting multiple hemostatic mechanisms. Several ii particle compositions were synthesized and then characterized through swelling studies, particle sizing, Scanning Electron Microscopy (SEM), and Fourier Transform Infrared Spectroscopy (FTIR). The in vitro interactions of the particles were evaluated through coagulation, degradation, platelet aggregation, and cytotoxicity studies. The results indicate that 4% alginate, 1% chitosan, 4% zeolite-loaded hydrogel beads can significantly reduce time to coagulation and increase platelet aggregation in vitro. Future research can look into the efficacy of these particles in vivo.

In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads

In recent years, the use of swelling polymeric matrices for the encapsulation and controlled release of protein drugs has received significant attention. The purpose of the present study was to investigate the release of albumin, a model protein from alginate/hydroxypropyl-methylcellulose (HPMC) gel beads. A hydrogel system comprised of two natural, hydrophilic polymers; sodium alginate and HPMC was studied as a carrier of bovine serum albumin (BSA) which was used as a model protein. The morphology, bead size and the swelling ratio were studied in different physical states; fully swollen, dried and reswollen using scanning electron microscopy and image analysis. Finally the effect of different alginate/HPMC ratios on the BSA release profile in physiological saline solution was investigated. Swelling experiments revealed that the bead diameter increases with the viscosity of the alginate solution while the addition of HPMC resulted in a significant increase of the swelling ratio. The BSA release patterns showed that the addition of HPMC increased the protein-release rate while the release mechanism fitted the Peppas model. Alginate/HPMC beads prepared using the ionic gelation exhibited high BSA loading efficiency for all formulations. The presence of HPMC increased the swelling ability of the alginate beads while the particle size remained unaffected. Incorporation of HPMC in the alginate gels also resulted in improved BSA release in physiological saline solution. All formulations presented a non-Fickian release mechanism described by the Peppas model. In addition, the implementation of non-parametric tests showed significant differences in the release patterns between the alginate/HPMC and the pure alginate beads, respectively.