Rotenone encapsulated in pH-responsive alginate-based microspheres reduces toxicity to zebrafish.

Rotenone is a botanical pesticide and has long been used for control of insect pests and also as a natural piscicide for management of fish populations in many countries. Field application for pest control, however, often encounters the movement of rotenone into surface water due to spray drift or surface runoff after rainfall, which could potentially result in water pollution and unexpected death of fishes. To minimize its effect on freshwater and the problem of fish dying, one solution was to encapsulate rotenone in specific microspheres, limiting its release and reducing its toxicity since rotenone can be quickly degraded under sunlight. In this study, pH-responsive alginate-based microspheres were synthesized to encapsulating rotenone, which were designated as rotenone beads. The rotenone beads, along with alginate beads (devoid of rotenone) were characterized and evaluated for their responses to pH and effects on zebrafish. Results showed that the microspheres had high loading efficiency (4.41%, w/w) for rotenone, and rotenone beads well responded to solution pH levels. The cumulative release rates of rotenone from the beads were 27.91%, 42.72%, and 90.24% at pH 5.5, 7.0, and 9.0, respectively. Under acidic conditions, the rotenone release rate was lower due to hydrogen bonding. On the contrary, rotenone became more quickly released at the high pH due to intermolecular repulsion. The toxicity of rotenone beads to zebrafish and fish embryos at a pH of 5.5 was reduced by 2- and 4-fold than chemical rotenone. Since pH levels in most freshwater lakes, ponds, and streams vary from 6 to 8, rotenone release from the beads in such freshwater could be limited. Thus, the synthesized rotenone beads could be relatively safely used for pest control with limited effects on freshwater fishers.

Surface functionalized magnetic nanoparticles shift cell behavior with on/off magnetic fields.

Magnetic nanoparticles (MNPs) are used as contrast agents and targeted drug delivery systems (TDDS) due to their favorable size, surface charge, and magnetic properties. Unfortunately, the toxicity associated with MNPs limits their biological applications. Surface functionalization of MNPs with selective polymers alters the surface chemistry to impart better biocompatibility. We report the preparation of surface functionalized MNPs using iron oxide NPs (MNPs), poly (lactic-co-glycolic acid) (PLGA), and sodium alginate via co-precipitation, emulsification, and electro-spraying, respectively. The NPs are in the nanosize range and negatively charged. Morphological and structural analyses affirm the surface functionalized nanostructure of the NPs. The surface functionalized MNPs are biocompatible, and demonstrate enhanced intracellular delivery under an applied magnetic field (H), which evinces the targeting ability of MNPs. After NP treatment, the physico-mechanical properties of fibroblasts are decided by the selective MNP uptake under "on" or "off" magnetic field conditions. We envision potential use of biocompatible surface functionalized MNP for intracellular-, targeted-DDS, imaging, and for investigating cellular mechanics.

Synthesis and evaluation of anti-fungal activities of sodium alginate-amphotericin B conjugates.

Sodium alginate (SA) was oxidized using periodate and amphotericin B (AmB) was conjugated via imine and amine linkages to the oxidized alginate. Oxidization drastically reduced the molecular weight (MW) of the alginate. The conjugates were highly water-soluble to the extent of 1000mg/mL making them useful for therapeutic applications. SA-AmB conjugates derived from 20 and 50% oxidized alginate were non-toxic to HEK 293T and RAW 264.7 cell line at 100µg/mL and was also non-hemolytic to human blood at 100µg/mL. In vitro release of AmB into phosphate buffer from the imine conjugates was negligible with less than 0.2% of the drug released in 48h. Capping of residual aldehyde handles using 2-ethanolamine or glycine resulted in increased release of the drug in vitro. Injectable gels of gelatin crosslinked with oxidized alginate incorporating the SA-AmB conjugates as well as AmB were also fabricated and drug release was examined. In vitro release from the gel discs showed that AmB was released to the extent of 15-20% in 2days. The SA-AmB conjugates showed potent anti-fungal activity against C. albicans, C. neoformans and C. parapsilosis. The injectable gels seem to have potential for prolonged release of AmB when implanted.

In vitro and in vivo toxicity assessment of alginate/eudragit S 100-enclosed chitosan-calcium phosphate-loaded iron saturated bovine lactoferrin nanocapsules (Fe-bLf NCs).

Lactoferrin has been known to have antimicrobial properties. This research was conducted to investigate the toxicity of Alginate/EUDRAGIT® S 100-enclosed chitosan-calcium phosphate-loaded Fe-bLf nanocapsules (NCs) by in vitro and in vivo assays. Brine shrimp lethality assay showed that the LC50 value of NCs was more than 1mg/mL which indicated that NCs was not toxic to Brine shrimp. However, the LC50 values for the positive control potassium dichromate at 24h is 64.15µg/mL, which was demostrated the toxic effect against the brine shrimp. MTT cytotoxicity assay also revealed that NCs was not toxic against non-cancerous Vero cell line with IC50 values of 536µg/mL. Genotoxicity studies by comet assay on Vero cells revealed that NCs exerted no significant genotoxic at 100µg/mL without tail or shorter comet tail. Allium cepa root assay carried out at 125, 250, 500 and 1000µg/mL for 24h revealed that the NCs was destitute of significant genotoxic effect under experimental conditions. The results show that there is no significant difference (p>0.05) in mitotic index between the deionized water and NCs treated Allium cepa root tip cells. In conclusion, no toxicity was observed in NCs in this study. Therefore, nontoxic NCs has the good potential to develop as a therapeutic agent.

Novel oleyl amine-modified polymannuronic acid micelle loading tacrolimus for therapy of allergic conjunctivitis.

Marine polysaccharide-based nanomaterial attracted considerable attention due to its biocompatibility and biodegradability. Here, a novel polymannuronic acid derivative (PM-C18) was synthesized as nanocarrier modified with hydrophobic oleyl amine. Its structure was confirmed by Fourier-transformed infrared spectrometry and nuclear magnetic resonance. To investigate its function, we developed tacrolimus (FK506) loaded nanoparticle by self-assembling PM-C18 and studied its drug loading, cytotoxicity and mechanism of in vitro release. Furthermore, we established a mouse model of allergic conjunctivitis (AC) to evaluate the efficacy of FK506 loaded PM-C18. The results indicated that PM-C18 carrier can encapsule FK506 with high drug loading (18%) and average particle size of 110.34±1.6nm. The release mechanism was diffusion initially followed a lasting release induced by swelling and collapse of PM-C18. One-week treatment with FK506 loaded PM-C18 efficiently relieved the symptoms of AC, which indicated it could serve as a potential ophthalmic drug for patients with AC. Compared with FK506 ophthalmic suspension, FK506 loaded PM-C18 improved medication adherence. Most importantly, we developed a novel versatile nanomaterial of PM-C18 which could encapsule other active agents for more applications.

Preparation and biocompatibility of demineralized bone matrix/sodium alginate putty.

Demineralized bone matrix (DBM) powder is widely used for bone regeneration due to its osteoinductivity and osteoconductivity. However, difficulties with handling, tendency to migrate from graft sites and lack of stability after surgery sometimes limit the clinical utility of this material. In this work, the possibility of using sodium alginate (ALG) carrier to deliver DBM powder was assessed. DBM-ALG putty with the DBM:ALG weight ratio of 5:5, 6:4, 7:3, 8:2 were prepared, respectively. The properties of the formed composite, including discrete degree, washout property, pH, equilibrium swelling as well as cytotoxicity in vivo, were adopted to ascertain the optimal ratio of DBM and ALG. The discrete diameter increased from 1.25 cm (5:5) to 2.08 cm (8:2) with the increase of DBM content. There was significant difference between the 8:2 group and the other groups in discrete diameter. The ratio of DBM had a significant effect on the swelling value. The pH of composites showed an increase trend with the DBM ratio's increase, when the ratio reached 7:3, the pH (7.22) was approximately equal to the body fluid. The proliferation of MC3T3-E1 cells was inhibited in the 5:5, 6:4 and 7:3 groups, while a slightly increased in the 8:2 group. The DBM-ALG with the optimal ratio of 7:3 was confirmed based on the results of the above mentioned. The histocompatibility of DBM-ALG (7:3) was examined using a rat model in which the materials were implanted subcutaneously, compared with the polyethylene, ALG and DBM. The study in vivo showed DBM-ALG (7:3) had a lower inflammatory response than DBM, a higher vascularization than ALG. The osteoinduction of DBM-ALG (7:3) was evaluated by co-culturing with MC3T3-E1 in vitro, compared with the DMEM, ALG and DBM. The results indicated calcification area in the DBM-ALG group was similar to that in the DBM group, larger than ALG group and DMEM group. The DBM-ALG (7:3) putty is promising as a directly injectable graft for repair of bone defect.

Injectable alginate-microencapsulated canine adipose tissue-derived mesenchymal stem cells for enhanced viable cell retention.

The purpose of this study was to establish an optimized protocol for the production of alginate-encapsulated canine adipose-derived mesenchymal stem cells (cASCs) and evaluate their suitability for clinical use, including viability, proliferation and in vivo cell retention. Alginate microbeads were formed by vibrational technology and the production of injectable microbeads was performed using various parameters with standard methodology. Microbead toxicity was tested in an animal model. Encapsulated cASCs were evaluated for viability and proliferation in vitro. HEK-293 cells, with or without microencapsulation, were injected into the subcutaneous tissue of mice and were tracked using in vivo bioluminescent imaging to evaluate the retention of transplanted cells. The optimized injectable microbeads were of uniform size and approximately 250 µm in diameter. There was no strong evidence of in vivo toxicity for the alginate beads. The cells remained viable after encapsulation, and there was evidence of in vitro proliferation within the microcapsules. In vivo bioluminescent imaging showed that alginate encapsulation improved the retention of transplanted cells and the encapsulated cells remained viable in vivo for 7 days. Encapsulation enhances the retention of viable cells in vivo and might represent a potential strategy to increase the therapeutic potency and efficacy of stem cells.

In vitro heterogeneous degradation of alginate and its validation of different molecular weight on blood bio-compatibility.

In the present work, sodium alginate (ALG) was degraded by heterogeneous phase acid degradation. The molecular weight distribution of ALG after degradation was close to homogenization. Then the blood bio-compatibility of ALG with different molecular weights (ALG-0h 50,075, ALG-0.5h 20,680, ALG-2h 13,170 and ALG-96h 1170 kDa) was evaluated in vitro and vivo. The human umbilical vein endothelial cells were used to assess the cytotoxicity of ALGs, ALG-0.5h and ALG-2h exhibited greater increment in percentage of cell viability comparing with ALG-0h and ALG-96h. With increasing of molecular weight of ALG, the blood clotting time was shortened and the hemolysis rate was slightly decreased. The different degree aggregation of red blood cells (RBCs) was observed in the ALG with different molecular groups and ALG-0h caused a severe aggregation of RBCs. Hematology analysis in vivo behavior after intraperitoneal (i.p.) injection indicated ALG-0h could cause blood solidification. Above results provided a reference for molecular weight selection in different applications.

Evaluation of alginate hydrogel cytotoxicity on three-dimensional culture of type A spermatogonial stem cells.

The culture of spermatogonial cells for future transplantation, based on the specific biology of these cells is important and necessary. Recently, the use of scaffolds especially alginate for culturing stem cells has been the focus of many researchers. The aim of this study was to evaluate the cytotoxicity of alginate hydrogels to cultures of type A spermatogonial stem cells. Spermatogonial stem cells of 6day-old immature mice were isolated by surgery; thereafter, the cells were purified by MACS using antibodies against thy-1 and C-kit and cultured on a layer of laminin. After purification, spermatogonial stem cells were encapsulated in alginate hydrogels. After one month of encapsulation and culture in DMEM culture medium containing 10ng/ml GDNF, cells were removed from hydrogel and were examined for viability, cell morphology and structure, cytotoxicity and expression of apoptosis genes Fas, P53, Bax, Bcl2, Caspase3 by staining with trypan blue, scanning electron microscopy, LDH test, and Real time PCR, respectively. The encapsulation did not change the morphology and viability of spermatogonial stem cells. Investigations showed that spermatogonial stem cells preserve by the high viability (74.08%) and cytotoxicity of alginate hydrogel was estimated to be 5%. Expression of Fas gene increased in main group compared with the control group, and expression of Bax and P53 was reduced in main group compared with the control group. Expression of Bcl2 and Caspase3 genes did not show any significant difference between the main group and the control group. Considering the lack of cytotoxicity and antioxidant properties of alginate hydrogel scaffold and high viability of cells, this three-dimensional scaffold is applicable for culturing and encapsulation of spermatogonial stem cells.

Guar gum succinate-sodium alginate beads as a pH-sensitive carrier for colon-specific drug delivery.

Guar gum succinate - sodium alginate (GGS-SA) beads cross-linked with barium ions were prepared and characterized as a pH sensitive carrier for colon-specific drug delivery. The structure of GGS-SA beads was confirmed by FT-IR spectroscopy. Scanning Electron Microscope (SEM) studies revealed that the drug loaded GGS-SA beads prepared using 2:2 (w/v) weight percent of GGS and SA had a diameter about 1.4mm and roughly spherical in shape. X-ray diffraction (XRD) studies showed that the peaks corresponding to GGS and SA at 13.5°, 17.5°, 20.2° and 13.5°, 22°, 24.1°, respectively were destroyed in GGS-SA beads which show that these beads are more amorphous in nature. Swelling studies demonstrated the pH-dependent swelling behavior of GGS-SA beads. The beads showed higher swelling degrees in pH 7.4 than that in pH 1.2 due to the existence of anionic groups in the polymer chains. The drug release study showed that the amount of model drug, ibuprofen, released from the GGS-SA beads was higher in pH 7.4 than that in pH 1.2 due to the pH-dependent swelling behavior of the beads. MTT assay revealed that GGS-SA beads at a concentration range of 0-30µg/ml had no cytotoxic effect on the cultured mouse mesenchymal stem cells (C3H10T1/2). These results suggest that GGS-SA beads can be used as effective colon-specific drug delivery system with pH-dependent drug release ability.

Nanoparticles based on phenylalanine ethyl ester-alginate conjugate as vitamin B2 delivery system.

Phenylalanine ethyl ester (PAE)-alginate (Alg) conjugate (PAE-Alg, PEA) was synthesized and formation of an amide bond between PAE and Alg was confirmed by Fourier transformed-infrared and (1)H nuclear magnetic resonance spectroscopy. The degree of PAE substitution was 3.5-4.7 (PAE group per hundred sugar residues of Alg) which was determined by elemental analysis. The critical aggregation concentration values determined for PEA conjugates PEA1, PEA2, and PEA3 were 0.20, 0.12, and 0.10 mg/ml, respectively. The particle size of PEA nanoparticles (PEA-NPs) decreased from 425 nm to 226 nm with the increasing degree of PAE substitution. Vitamin B2 (VB2), as a model nutrient, was encapsulated into the nanoparticles. The drug-loading content increased with increasing degree of PAE substitution. The maximum VB2 loading capacity and loading efficiency of PEA3 nanoparticles were 3.53 ± 0.03% and 91.48 ± 0.80%, respectively. The in vitro release behavior of VB2 from the PEA-NPs showed a biphasic release profile with an initial burst release of about 40-50% of VB2 in the first 10 h followed by a steady and continuous release phase for the following 50 h in PBS, pH 7.4. The human colorectal carcinoma cell line was used to investigate the cytotoxicity of PEA-NPs. Our results showed that various concentrations of nanoparticles did not cause significant cytotoxicity against cell lines at normal concentrations.

Comparison of the cytotoxicities and wound healing effects of hyaluronan, carbomer, and alginate on skin cells in vitro.

OBJECTIVE: To compare the cytotoxicities and efficacy of hyaluronan (HA), carbomer, and sodium alginate on repairing thermal-injured cells and promoting cell migration. DESIGN: The 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetra-zoliumromide method was used to evaluate the cytotoxicities of HA, carbomer, and sodium alginate on L929 mouse fibroblasts and their repairing ability to thermal-injured HaCaT keratinocytes. A scratch test was used to observe the effects of the 3 materials on cell migration. RESULTS: Hyaluronan with different molecular weights were nontoxic, even at the concentration of 0.5%, whereas carbomer and sodium alginate showed mild or moderate cytotoxicities when their concentrations were higher than 0.1%. Cell viability and cell density of the thermal-injured keratinocytes treated with HA (600, 1070, and 1500 kDa) were increased significantly compared with that of model control (P < .05), whereas carbomer aggravated cell injury, and sodium alginate had no obvious repairing ability. Hyaluronan promoted cell migration significantly with higher cell density in the scratch area, compared with the control after culture for 48 hours; both carbomer and sodium alginate inhibited the cell migration, and carbomer altered the cell morphology completely. CONCLUSIONS: Hyaluronan can repair cell injury and promote cell migration and proliferation. It also has good biocompatibility. As a new type of hydrogel matrix, HA is superior to carbomer and sodium alginate if it is used in wound caring preparations.

Effects of alginate on stability and ecotoxicity of nano-TiO2 in artificial seawater.

The large-scale use of titanium dioxide nanoparticles (nano-TiO2) in consumer and industrial applications raised environmental health and safety concerns. Potentially impacted ecosystems include estuarine and coastal organisms. Results from ecotoxicological studies with nano-TiO2 dispersed in salt exposure media are difficult to interpret due to fast flocculation and sedimentation phenomena affecting the dispersion stability. The goal of this study was to investigate the stabilisation effect of alginate on uncoated nano-Ti22 in artificial seawater dispersions used in ecotoxicity bioassays. The most effective stabilisation was obtained at alginate concentration of 0.45 g/L after sonicating dispersions for 20 min (100 W). The size distribution remained constant after re-suspension, indicating that no agglomeration occurred after deposition. Ecotoxicity tests on Artemia franciscana and Phaeodactylum tricornutum did not show any adverse effects related to the presence of alginate in the exposure media, and provided evidence on possible reduced bioavailability of nano-TiO2. The suitable concentration of alginate is recommended to occur on a case-by-case basis.

Effects of experimental craniofacial pain on fine jaw motor control: a placebo-controlled double-blinded study.

The aim of the experiment was to test the hypothesis that experimental pain in the masseter muscle or temporomandibular joint (TMJ) would perturb the oral fine motor control, reflected in bigger variability of bite force values and jaw muscle activity, during repeated splitting of food morsels. Twenty healthy volunteers participated in four sessions. An intervention was made by injection of either 0.2 ml of monosodium glutamate/isotonic saline (MSG/IS) (randomized) in either the masseter or TMJ (randomized). The participants were asked to hold and split a flat-faced placebo tablet with their anterior teeth, thirty times each at baseline, during intervention and post-intervention. Pain was measured using a 0-10 visual analog scale. The force applied by the teeth to "hold" and "split" the tablet along with the corresponding electromyographic (EMG) activity of the jaw muscles and subject-based reports on perception of pain was recorded. The data analysis included a three-way analysis of variance model. The peak pain intensity was significantly higher during the painful MSG injections in the TMJ (6.1 ± 0.4) than the injections in masseter muscle (5.5 ± 0.5) (P = 0.037). Variability of hold force was significantly smaller during the MSG injection than IS injection in the masseter (P = 0.024). However, there was no significant effect of intervention on the variability of split force during the masseter injections (P = 0.769) and variability of hold and split force during the TMJ injections (P = 0.481, P = 0.545). The variability of the EMG activity of the jaw muscles did not show significant effects of intervention. Subject-based reports revealed that pain did not interfere in the ability to hold the tablet in 57.9 and 78.9 %, and the ability to split the tablet in 78.9 and 68.4 %, of the participants, respectively, during painful masseter and TMJ injections. Hence, experimental pain in the masseter muscle or TMJ did not have any robust effect in terms of bigger variability of bite force and jaw muscle activity, during repeated splitting of food morsels.

Bioresorbable ureteral stents from natural origin polymers.

In this work, stents were produced from natural origin polysaccharides. Alginate, gellan gum, and a blend of these with gelatin were used to produce hollow tube (stents) following a combination of templated gelation and critical point carbon dioxide drying. Morphological analysis of the surface of the stents was carried out by scanning electron microscopy. Indwelling time, encrustation, and stability of the stents in artificial urine solution was carried out up to 60 days of immersion. In vitro studies carried out with simulated urine demonstrated that the tubes present a high fluid uptake ability, about 1000%. Despite this, the materials are able to maintain their shape and do not present an extensive swelling behavior. The bioresorption profile was observed to be highly dependent on the composition of the stent and it can be tuned. Complete dissolution of the materials may occur between 14 and 60 days. Additionally, no encrustation was observed within the tested timeframe. The ability to resist bacterial adherence was evaluated with Gram-positive Staphylococcus aureus and two Gram-negatives Escherichia coli DH5 alpha and Klebsiella oxytoca. For K. oxytoca, no differences were observed in comparison with a commercial stent (Biosoft(®) duo, Porges), although, for S. aureus all tested compositions had a higher inhibition of bacterial adhesion compared to the commercial stents. In case of E. coli, the addition of gelatin to the formulations reduced the bacterial adhesion in a highly significant manner compared to the commercial stents. The stents produced by the developed technology fulfill the requirements for ureteral stents and will contribute in the development of biocompatible and bioresorbable urinary stents.

A comparison between ultraviolet disinfection and copper alginate beads within a vortex bioreactor for the deactivation of bacteria in simulated waste streams with high levels of colour, humic acid and suspended solids.

We show in this study that the combination of a swirl flow reactor and an antimicrobial agent (in this case copper alginate beads) is a promising technique for the remediation of contaminated water in waste streams recalcitrant to UV-C treatment. This is demonstrated by comparing the viability of both common and UV-C resistant organisms in operating conditions where UV-C proves ineffective - notably high levels of solids and compounds which deflect UV-C. The swirl flow reactor is easy to construct from commonly available plumbing parts and may prove a versatile and powerful tool in waste water treatment in developing countries.

Cytotoxic effects of denture adhesives on primary human oral keratinocytes, fibroblasts and permanent L929 cell lines.

BACKGROUND: To date, there have been very little data on the cytotoxic responses of different cell lines to denture adhesives. OBJECTIVE: To determine the cytotoxicity of three denture adhesives on primary human oral keratinocytes (HOKs), fibroblasts (HOFs) and permanent mouse fibroblasts cell lines (L929). METHODS: Three commercial denture adhesives (two creams and one powder) were prepared for indirect contact using the agar diffusion test, as well as extracts in MTT assay. The results of the MTT assay were statistically analysed by one-way anova and Tukey's test (p < 0.05). RESULTS: All of the tested denture adhesives showed mild to moderate cytotoxicity to primary HOKs (p < 0.001), whereas none of three was toxic to L929 cells (p > 0.05) in both assays. For primary HOFs cultures, slight cytotoxicity was observed for one of the products from the agar diffusion test and undiluted eluates of all tested adhesives with MTT assay (p < 0.01). CONCLUSION: Denture adhesives are toxic to the primary HOKs and HOFs cultures, whereas non-toxic to L929 cells. The results suggest that primary human oral mucosal cells may provide more valuable information in toxicity screening of denture adhesives.

The influence of polymeric component of bioactive glass-based nanocomposite paste on its rheological behaviors and in vitro responses: hyaluronic acid versus sodium alginate.

Different biocomposite pastes were prepared from a solid phase that was nanoparticles of sol-gel-derived bioactive glass and different liquid phases including 3% hyaluronic acid solution, sodium alginate solutions (3% and 10 %) or mixtures of hyaluronic acid and sodium alginate (3% or 10 %) solutions in 50:50 volume ratio. Rheological properties of the pastes were measured in both rotatory and oscillatory modes. The washout behavior and in vitro apatite formation of the pastes were determined by soaking them in simulated body fluid under dynamic situation for 14 days. The proliferation and alkaline phosphatase activity of MG-63 osteoblastic cells were also determined using extracts of the pastes. All pastes could be easily injected from the standard syringes with different tip diameters. All pastes exhibited visco-elastic character, but a nonthixotropic paste was obtained using hyaluronic acid in which the loss modulus was higher than the storage modulus. The thixotropy and storage modulus were increasingly improved by adding/using sodium alginate as mixing liquid. Moreover, the pastes in which the liquid phase was sodium alginate or mixture of hyaluronic acid and 10% sodium alginate solution revealed better apatite formation ability and washout resistance than that made of hyaluronic acid alone. No cytotoxicity effects were observed by extracts of the pastes on osteoblasts but better alkaline phosphatase activity was found for the pastes containing hyaluronic acid. Overall, injectable biocomposites can be produced by mixing bioactive glass nanoparticles and sodium alginate/hyaluronic acid polymers. They are potentially useful for hard and even soft tissues treatments.

Fabrication and characterization of monodisperse PLGA-alginate core-shell microspheres with monodisperse size and homogeneous shells for controlled drug release.

Monodisperse PLGA-alginate core-shell microspheres with controlled size and homogeneous shells were first fabricated using capillary microfluidic devices for the purpose of controlling drug release kinetics. Sizes of PLGA cores were readily controlled by the geometries of microfluidic devices and the fluid flow rates. PLGA microspheres with sizes ranging from 15 to 50µm were fabricated to investigate the influence of the core size on the release kinetics. Rifampicin was loaded into both monodisperse PLGA microspheres and PLGA-alginate core-shell microspheres as a model drug for the release kinetics studies. The in vitro release of rifampicin showed that the PLGA core of all sizes exhibited sigmoid release patterns, although smaller PLGA cores had a higher release rate and a shorter lag phase. The shell could modulate the drug release kinetics as a buffer layer and a near-zero-order release pattern was observed when the drug release rate of the PLGA core was high enough. The biocompatibility of PLGA-alginate core-shell microspheres was assessed by MTT assay on L929 mouse fibroblasts cell line and no obvious cytotoxicity was found. This technique provides a convenient method to control the drug release kinetics of the PLGA microsphere by delicately controlling the microstructures. The obtained monodisperse PLGA-alginate core-shell microspheres with monodisperse size and homogeneous shells could be a promising device for controlled drug release.

Alginate enhances excretion and reduces absorption of strontium and cesium in rats.

Alginate (ALA), which is an intercellular polysaccharide associated with brown algae, is used as a food additive, a health food and a medicine. Here, we first examined the adsorption of strontium (Sr) and cesium (Cs) by ALA in vitro, and then evaluated the effects of ALA on absorption and excretion of Sr and Cs in rats, in order to evaluate its potential usefulness for minimizing radiation damage from materials released after a nuclear accident. Both Sr and Cs were concentration-dependently adsorbed by sodium alginate (ALA-Na) in vitro. In rats given diet containing either ALA-Na or calcium alginate (ALA-Ca) for two weeks, the plasma concentration of Sr gradually decreased compared with the controls (normal diet); however, in the case of Cs, the plasma concentration was decreased only in the ALA-Ca group, but not the ALA-Na group. Moreover, we examined the effect of preadministration of diet containing either ALA-Na or ALA-Ca on absorption of Sr and Cs administered orally as the chloride salts to rats. Absorption of both Sr and Cs was reduced in the ALA-Ca group, while absorption of only Sr was reduced in the ALA-Na group. Safety assessments indicated that ALA-Ca is safer than ALA-Na. These results indicate that ALA-Ca reduces absorption and promotes excretion of both Sr and Cs, while ALA-Na does so only for Sr.