Development of novel gastroretentive salbutamol sulfate-loaded sodium alginate-pectin bubble beads prepared by co-axial needle air-injection method and in vivo clinical evaluation by ultrasound studies.

In the present study, the salbutamol sulfate-loaded sodium alginate-pectin (SS-loaded SA-PEC) bubble beads have been optimized and evaluated for drug loading, in vitro drug release, in vivo floating behavior in the stomach, etc. Nine batches (F1-F9) of bubble beads with different SA and PEC contents were prepared by novel co-axial needle air-injection method and related to their percent drug loading efficiency (%DLE) and percent drug release at 4 h (%R4h) as response factors. The multivariate analysis has shown the effect of SA/PEC ratio, total polymer content, as well as their interaction on %DLE and %R4h. In the quantitative modeling, the satisfactory adjustment of the linear models (along with interaction terms) with the experimental data for both %DLE and %R4h has confirmed the findings of the multivariate analysis. The optimized SS-loaded SA-PEC bubble beads based on 2D (contours), 3D, desirability, and overlay plots has exhibited %DLE of 87.35 ±â€¯2.48% (n = 3 and error = 2.94%) and %R4h of 85.79 ±â€¯2.98% (n = 3 and error = 0.25%). The in vitro drug release studies have shown almost complete (≥85%) SS release from all the batches within 4-6 h in simulated gastric fluid (SGF) pH 1.2. The in vivo clinical findings by ultrasound studies have shown excellent floatation (>6 h) behavior of bubble beads in the upper gastrointestinal tract (GIT) and efficient stomach-specific gastroretention.

Pea-protein alginate encapsulation adversely affects development of clinical signs of Citrobacter rodentium-induced colitis in mice treated with probiotics.

The efficacy of two strains of Lactobacillus probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0052) immobilized in microcapsules composed of pea protein isolate (PPI) and alginate microcapsules was assessed using a mouse model of Citrobacter rodentium-induced colitis. Accordingly, 4-week-old mice were fed diets supplemented with freeze-dried probiotics (group P), probiotic-containing microcapsules (group PE) (lyophilized PPI-alginate microcapsules containing probiotics), or PPI-alginate microcapsules containing no probiotics (group E). Half of the mice (controls, groups P, PE, and E) received C. rodentium by gavage 2 weeks after initiation of feeding. Daily monitoring of disease symptoms (abnormal behavior, diarrhea, etc.) and body weights was undertaken. Histopathological changes in colonic and cecal tissues, cytokine expression levels, and pathogen and probiotic densities in feces were examined, and the microbial communities of the distal colon mucosa were characterized by 16S rRNA sequencing. Infection with C. rodentium led to marked progression of infectious colitis, as revealed by symptomatic and histopathological data, changes in cytokine expression, and alteration of composition of mucosal communities. Probiotics led to changes in most of the disease markers but did not have a significant impact on cytokine profiles in infected animals. On the basis of cytokine expression analyses and histopathological data, it was evident that encapsulation materials (pea protein and calcium alginate) contributed to inflammation and worsened a set of symptoms in the cecum. These results suggest that even though food ingredients may be generally recognized as safe, they may in fact contribute to the development of an inflammatory response in certain animal disease models.

Effect of microencapsulated probiotic Bacillus vireti 01-polysaccharide extract of Gracilaria folifera with alginate-chitosan on immunity, antioxidant activity and disease resistance of Macrobrachium rosenbergii against Aeromonas hydrophila infection.

Polysaccharide from red seaweed Gracilaria folifera has an interesting functional property of antioxidant activity and prebiotic effect. A feeding trial experiment was directed to examine the effect of probiotic bacteria Bacillus vireti 01 microencapsulated with G. folifera polysaccharide against freshwater prawn M. rosenbergii. Three different feeding trials were conducted for 15 days. The first group contained prawns fed with commercial diet. The second group was comprised of Aeromonas hydrophila challenged prawns fed with commercial feed. The third group consisted of A. hydrophila challenged prawns fed with microencapsulated probiotic-polysaccharide. Survival percentage was significantly decreased in prawns of group2 as compared to that of group1 and group3 prawns (p < 0.0001). The immunological parameters and antioxidant activities (p < 0.001) were found to be increased in group three prawns which were fed with encapsulated probiotic-seaweed polysaccharide and challenged with A. hydrophila as compared to that of group1 and group2. Tissue necrosis, fused lamella, haemocyte infiltration and damage of hepatopancreas lumen and tubule were noted in group2 prawns. There was no histological changes were observed in group3 prawns in which the histological architecture was similar to the control group1. The results suggested that combination of encapsulated probiotic B. vireti 01 and seaweed polysaccharide as dietary feed showed an enhancement of immune response, antioxidant activity and disease resistant of M. rosenbergii against A. hydrophila.

Reactogenicity and safety assessment of an attenuated nanovaccine against scorpion envenomation: Preclinical study.

An attenuated nanovaccine (Nps - V∗) has been developed to protect humans from fatal scorpion envenomation in at-risk regions. This study was conducted to evaluate the toxicity and the local reactogenicity of the Nps - V∗ nanovaccine developed against Androctonus australis hector (Aah) venom. Assessment of the systemic inflammatory response and serum cytokine levels were evaluated in vaccinated mice with 100µg of irradiated Aah venom (V∗) encapsulated or not into polymeric calcium-alginate nanoparticles (Nps) and injected by subcutaneous (s.c) route. The local reactogenicity was evaluated by dermal Draize observations and skin tissue analysis at the injection site of vaccinated rabbits with 250 or 500µg of V∗-loaded into Nps. All animals gained weight and had normal food consumption during the study. Additionally, results showed that the nanoformulation Nps - V∗ did not cause clinical evidence of systemic toxicity in mice or rabbits, a transient edema/erythema at the injection site was only recorded as treatment-related reactogenicity. These results indicated a favorable safety profile for Nps - V∗ and supported its use in superior animal tests, then in a Phase 1 clinical trial.

Lipid/alginate nanoparticle-loaded in situ gelling system tailored for dexamethasone nasal delivery.

In this study, we suggest the development of nanoparticle loaded in situ gelling system suitable for corticosteroid nasal delivery. We propose lipid/alginate nanoparticles (size 252.3±2.4nm, polydispersity index 0.241, zeta-potential -31.7±1.0mV, dexamethasone (Dex) content 255±7µgml-1) dispersed in pectin solution (5mgml-1) that undergoes a sol-gel phase transition triggered by Ca2+ present in nasal mucosa. The viscoelasticity of gel obtained by mixing nanoparticle suspension in pectin continuous phase with simulated nasal fluid (1:1V/V) is characterised by a log-linear shear thinning viscosity behaviour. Observed viscosity corresponds to the range of viscosities of nasal mucus at physiological as well as under disease conditions. Nanoparticle-loaded gel was biocompatible with the selected epithelial cell model and, in comparison to dexamethasone solution, provided reduction in Dex release (t50% 2.1h and 0.6h, respectively) and moderated transepithelial permeation in vitro (Papp 7.88±0.15 and 9.73±0.57×10-6cms-1, respectively). In conclusion, this study showed the potential of the proposed system to provide local therapeutic effect upon administration of a lower corticosteroid dose and minimize the possibility for adverse effects as it can be easily sprayed as solution and delivered beyond nasal valve, ensure prolonged contact time with nasal mucosa upon gelation, and moderate corticosteroid release and permeation.

A New Vaccine Delivery Vehicle and Adjuvant Candidate: Bordetella pertussis Inactivated Whole Cells Entrapped in Alginate Microspheres.

There is no doubt about the whole cell pertussis vaccine efficacy, but it is necessary to improve the vaccine quality specially to decrease its toxicity by obtaining good immunogenicity with low bacterial content. In this work, under optimum condition inactivated B. pertussis bacteria cells entrapped with alginate microparticles were fabricated and in vivo immunogenicity and ptency of new microparticle based vaccine were evaluated in mice. Microspheres loaded with inactive B. pertussis bacterium cells were prepared via an emulsification method and analyzed for morphology, size, polydispersity index, loading efficiency, loading capacity, release profile and in vivo potency. The inactivated bacterial suspension mixture prepared in this work was nontoxic and showed potent ED50 (1:333 of human dose) and preserved agglutinins 1, 2, 3. The optimum conditions for the preparation of microparticles were achieved at alginate concentration 3.8% (w/v), CaCl2 8% (w/v), PLL 0.1% (w/v), lipophilic surfactant 0.22 (%w/v), hydrophilic surfactant 3.6 (%w/v), cross linking time 3min, homogenization rate 600 rpm, and alginate to CaCl2 solution ratio 4. Both empty and B. pertussis loaded microparticles exhibited smooth surface texture and relatively spherical shape. The B. pertussis encapsulated microspheres fabricated under optimized conditions showed mean particle size 151.1 µm, polydispersity index 0.43, loading efficiency 89.6%, loading capacity 36.3%, and relatively constant release rate lasted to 15 days. In vivo immunogenicity and protection study against wild type challenge showed strongly higher potency (approximately 2.5 fold) of encapsulated B. pertussis organisms than non-encapsulated conventional aluminum hydroxide adsorbed vaccine. It can be concluded that microencapsulation of inactive B. pertussis cells appears to be a suitable approach for improving the wP vaccine quality, specially by obtaining good immunogenicity with low bacterial content.

Floating mucoadhesive alginate beads of amoxicillin trihydrate: A facile approach for H. pylori eradication.

This study investigates the design of sunflower oil entrapped floating and mucoadhesive beads of amoxicillin trihydrate using sodium alginate and hydroxypropyl methylcellulose as matrix polymers and chitosan as coating polymer to localize the antibiotic at the stomach site against Helicobacter pylori. Beads prepared by ionotropic gellation technique were evaluated for different physicochemical, in-vitro and in-vivo properties. Beads of all batches were floated for >24h with a maximum lag time of 46.3±3.2s. Scanning electron microscopy revealed that the beads were spherical in shape with few oil filled channels distributed throughout the surfaces and small pocket structures inside the matrix confirming oil entrapment. Prepared beads showed good mucoadhesiveness of 75.7±3.0% to 85.0±5.5%. The drug release profile was best fitted to Higuchi model with non fickian driven mechanism. The optimized batch showed 100% Helicobacter pylori growth inhibition in 15h in in-vitro culture. Furthermore, X-ray study in rabbit stomach confirmed the gastric retention of optimized formulation. The results exhibited that formulated beads may be preferred to localize the antibiotic in the gastric region to allow more availability of antibiotic at gastric mucus layer acting on Helicobacter pylori, thereby improving the therapeutic efficacy.

Innovative formulation of nystatin particulate systems in toothpaste for candidiasis treatment.

Oral candidiasis is a mycosis on the mucous membranes of the mouth but not limited to the mouth. Nystatin is one of the most frequently employed antifungal agents to treat infections and may be safely given orally as well as applied topically but its absorption through mucocutaneous membranes such as the gut and the skin is minimal. The purpose of this study is to enhance the effectiveness of nystatin using particulate system such as beads, micro- and nanoparticles of alginate incorporated into toothpaste. Those particulate systems of nystatin were prepared by extrusion/external gelation for beads and emulsification/internal gelation for micro- and nanoparticles and characterized. Small, anionic charged and monodispersed particles were successfully produced. The type of particulate system influenced all previous parameters, being microparticles the most suitable particulate system of nystatin showing the slowest release, the highest inhibitory effect of Candida albicans over a period of one year. Those results allowed the conclusion that alginate exhibits properties that enable the in vitro functionality of encapsulated nystatin and thus may provide the basis for new successful approaches for the treatment of oral antifungal infections such as oral candidiasis.

Alterative effects of an oral alginate extract on experimental rabbit osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly. However, few agents with high efficacy and low side effects have been developed to treat OA. In this study, we evaluated the effects of the alginate extract named CTX in OA cell and rabbit models. RESULTS: CTX was formulated by hydrolyzing sodium alginate polymers with alginate lyase and then mixing with pectin. HPLC was used to analyze the CTX content. Human chondrosarcoma SW1353 cells treated with interleukin-1ß were used as OA model cells to investigate the effects of CTX on chondrocyte inflammation and anabolism. CTX at concentrations up to 1000 µg/ml exerted low cytotoxicity. It inhibited the gene expression of proinflammatory matrix metalloproteinases (MMPs) including MMP1, MMP3 and MMP13 in a dose-dependent manner and increased the mRNA level of aggrecan, the major proteoglycan in articular cartilage, at 1000 µg/ml. Thirteen-week-old New Zealand White rabbits underwent a surgical anterior cruciate ligament transection and were orally treated with normal saline, glucosamine or CTX for up to 7 weeks. Examinations of the rabbit femur and tibia samples demonstrated that the rabbits taking oral CTX at a dosage of 30 mg/kg/day suffered lesser degrees of articular stiffness and histological cartilage damage than the control rabbits. CONCLUSIONS: The gene expression profiles in the cell and the examinations done on the rabbit cartilage suggest that the alginate extract CTX is a pharmaco-therapeutic agent applicable for OA therapy.

Core-Shell Collagen Peptide Chelated Calcium/Calcium Alginate Nanoparticles from Fish Scales for Calcium Supplementation.

UNLABELLED: We report simple methods for preparing collagen peptide chelated calcium (cpcc) and a novel cpcc-loaded nanoparticle from marine fish scales for calcium supplementation. Cpcc nanoparticles have an average diameter of approximately 150 nm and a calcium content of up to 130.4 g/kg. Calcium alginate was selected to encapsulate cpcc for the preparation of core-shell cpcc/calcium alginate nanoparticles. The core-shell nanoparticles were mainly 200 to 500 nm in diameter. The ratio of calcium to sulfur was approximately 1.6:1. In vivo experiments indicated both cpcc and core-shell cpcc were able to improve calcium absorption and prevent calcium deficiency. Especially core-shell cpcc worked well to increase femur bone mineral density and femur calcium content in rats significantly. The study demonstrated that cpcc and core-shell cpcc nanoparticles were ideal for calcium supplementation. PRACTICAL APPLICATION: Calcium deficiency has become an increasingly relevant health concern in the food industry. There is an urgent need for new effective calcium supplements. This study consisted of preparing and characterizing alginate nanoparticles loaded with collagen peptide chelated calcium. These nanoparticles can enhance calcium absorption significantly and prevent calcium deficiency. The data presented in this study can aid the food industry in developing a new ideal calcium supplement.

Alginate dressings for treating pressure ulcers.

BACKGROUND: Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. Dressings are widely used to treat pressure ulcers and there are many options to choose from including alginate dressings. A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use for the treatment of pressure ulcers. This review is part of a suite of Cochrane reviews investigating the use of dressings in the treatment of pressure ulcers. Each review will focus on a particular dressing type. OBJECTIVES: To assess the effects of alginate dressings for treating pressure ulcers in any care setting. SEARCH METHODS: For this review, in April 2015 we searched the following databases the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions based on language or date of publication. SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) comparing the effects of alginate with alternative wound dressings or no dressing in the treatment of pressure ulcers (stage II or above). DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment and data extraction. MAIN RESULTS: We included six studies (336 participants) in this review; all studies had two arms. The included studies compared alginate dressings with six other interventions that included: hydrocolloid dressings, silver containing alginate dressings, and radiant heat therapy. Each of the six comparisons included just one study and these had limited participant numbers and short follow-up times. All the evidence was of low or very low quality. Where data were available there was no evidence of a difference between alginate dressings and alternative treatments in terms of complete wound healing or adverse events. AUTHORS' CONCLUSIONS: The relative effects of alginate dressings compared with alternative treatments are unclear. The existing trials are small, of short duration and at risk of bias. Decision makers may wish to consider aspects such as cost of dressings and the wound management properties offered by each dressing type, for example, exudate management.

Effect of sodium alginate addition to resveratrol on acute gouty arthritis.

OBJECTIVE: Resveratrol has been shown to exert anti-inflammatory and antioxidant effects, while sodium alginate is a common pharmaceutic adjuvant with antioxidative and immunomodulatory properties. We performed an animal study to investigate the effect of sodium alginate addition to resveratrol on acute gouty arthritis. METHODS: Twenty-four SPF Wistar mice were randomized to four groups receiving the combination of sodium alginate and resveratrol, resveratrol alone, colchicine, and placebo, respectively. Acute gouty arthritis was induced by injection of 0.05 ml monosodium urate (MSU) solution (25g/mL) into ankle joint cavity. IL-1ß, CCR5, and CXCL10 levels in both serum and synovial fluid were measured using ELISA. NLRP3 expression in the synovial tissues was measured using western plot. RESULTS: The combination of sodium alginate and resveratrol significantly reduced synovial levels of IL-1ß, CCR5, and CXCL10 when compared with colchicines, and all P values were less than 0.0001. The combination of sodium alginate and resveratrol was also superior to resveratrol in terms of both serum levels and synovial levels of IL-1ß, CCR5, and CXCL10. In addition, resveratrol, with or without sodium alginate, could reduce NLRP3 expression obviously in the synovial tissues. CONCLUSION: The combination of sodium alginate and resveratrol has better effect over colchicines in treating MSU-induced acute gouty arthritis.

Development of a novel adjuvanted nasal vaccine: C48/80 associated with chitosan nanoparticles as a path to enhance mucosal immunity.

In a time in which mucosal vaccines development has been delayed by the lack of safe and effective mucosal adjuvants, the combination of adjuvants has started to be explored as a strategy to obtain potent vaccine formulations. This study describes a novel adjuvant combination as an effective approach for a nasal vaccine - the association of the mast cell activator compound 48/80 with chitosan based nanoparticles. It was hypothesized that mucoadhesive nanoparticles would promote the cellular uptake and prolong the antigen residence time on nasal cavity. Simultaneously, mast cell activation would promote a local microenvironment favorable to the development of an immune response. To test this hypothesis, two different C48/80 loaded nanoparticles (NPs) were prepared: Chitosan-C48/80 NP (Chi-C48/80 NP) and Chitosan/Alginate-C48/80 NP (Chi/Alg-C48/80 NP). The potential as a vaccine adjuvant of the two delivery systems was evaluated and directly compared. Both formulations had a mean size near 500nm and a positive charge; however, Chi-C48/80 NP was a more effective adjuvant delivery system when compared with Chi/Alg-C48/80 NP or C48/80 alone. Chi-C48/80 NP activated mast cells at a greater extent, were better internalized by antigen presenting cells than Chi/Alg-C48/80 NP and successfully enhanced the nasal residence time of a model antigen. Superiority of Chi-C48/80 NP as adjuvant was also observed in vivo. Therefore, nasal immunization of mice with Bacillus anthracis protective antigen (PA) adsorbed on Chi-C48/80 NP elicited high levels of serum anti-PA neutralizing antibodies and a more balanced Th1/Th2 profile than C48/80 in solution or Chi/Alg-C48/80 NP. The incorporation of C48/80 within Chi NP also promoted a mucosal immunity greater than all the other adjuvanted groups tested, showing that the combination of a mast cell activator and chitosan NP could be a promising strategy for nasal immunization.

Effects of polymannuronate on performance, antioxidant capacity, immune status, cecal microflora, and volatile fatty acids in broiler chickens.

The aim of this study was to assess the effects of purified polymannuronate (PM) obtained from marine brown algae on the performance, antioxidant capacity, immune status, and cecal fermentation profile of broiler chickens. In a 42 d experiment, 540 (average BW 43.77±1.29 g) 1-d-old Arbor Acres male broilers were randomly divided into 5 treatments with 6 replicates of 18 chicks and fed a corn and soybean meal (SBM)-based diet supplemented with 0, 1, 2, 3, or 4 g/kg polymannuronate. Adding polymannuronate to the broiler chickens' diets resulted in a significantly increased ADG and improved feed conversion compared with the control treatment. From d 1 to 42, the ADG of broilers fed 1, 2, 3, or 4 g/kg of polymannuronate was increased by 2.58, 4.33, 4.20, and 3.47%, respectively. Furthermore, parameters related to immune status, antioxidant capacity, and composition of the cecal microflora in broiler chickens fed the polymannuronate-containing diets were altered compared with broiler chickens fed a diet without polymannuronate. Supplementation with polymannuronate significantly increased the concentrations of lactic acid and acetic acid in the cecum compared with the control group. The results indicate that polymannuronate has the potential to improve broiler chicken immune status, antioxidant capacity, and performance.

A novel amiodarone-eluting biological glue for reducing postoperative atrial fibrillation: first animal trial.

OBJECTIVE: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, leading to increased morbidity and mortality. The aim of this preliminary study was to evaluate a novel drug delivery system for local release of amiodarone. METHODS: In the current prospective study, 9 goats underwent attachment of right atrial (RA) epicardial electrodes. Alginate-based glue with amiodarone was applied to the RA of the treatment groups. Rapid atrial response (RAR) to burst pacing was assessed before application and in the third postoperative day (POD3). Average RAR frequency was defined as the average percentage of inductions resulting in RAR per animal. Myocardial and extracardiac tissue amiodarone concentrations were analyzed. RESULTS: Differences in RAR proportions between baseline and POD3 were greater in the treatment group versus the control group (P = .034). Average RAR frequency was reduced by 34% in the treatment group (baseline: 65%; POD3: 31%), while it was increased by 11.3% in the control (baseline:43.8%; POD3: 55%). The treatment group demonstrated a greater proportion of animals meeting the success criterion of net percentage reduction in RAR frequency greater than 25% (P = .047). The average amount of total amiodarone detected in the RA was 104.4 ± 28.9 µg; the transmural concentration was linearly distributed (P < .0001). Extracardiac tissue concentrations were below the detection level. CONCLUSIONS: Local alginate-based amiodarone delivery demonstrated an RAR frequency reduction of clinical importance in response to burst pacing. The electrophysiological response was achieved while maintaining below-detection systemic drug levels. Current findings may point to the system's future applicability in reducing POAF risk in humans.

Protective effect of a new biomaterial against the development of experimental osteoarthritis lesions in rabbit: a pilot study evaluating the intra-articular injection of alginate-chitosan beads dispersed in an hydrogel.

OBJECTIVE: This study aimed to evaluate the structural benefit of a new biomaterial composed of alginate-chitosan (AC) beads dispersed in a hydrogel (H) derived from chitosan on the development of osteoarthritis (OA) in rabbit. DESIGN: OA was induced by the surgical transection of the anterior cruciate ligament in rabbits. Animals received a single intra-articular injection (900 µl) of AC beads in H hydrogel, H hydrogel alone or saline a week after surgery. OA development was followed by X-rays. Blood samples were collected throughout the study to measure biological markers (Prostaglandins E2 - PGE2 and C reactive protein - CRP). Macroscopic observation and histological evaluation of articular cartilage and synovial membrane were performed 6 weeks after surgery. RESULTS: AC beads in H hydrogel prevented from the development of OA based on the reduction of the Kellgren & Lawrence (K&L) score. It also significantly reduced the histological score of cartilage lesion severity. This effect was homogenous on every joint compartment. It was due to a significant effect on cartilage structure and cellularity scores. The injection of AC beads in H hydrogel also tended to reduce the synovial membrane inflammation. No significant variation of biological markers was noted. CONCLUSIONS: The present pilot study provides interesting and promising results for the use of AC beads in H hydrogel in animal. It indeed prevented the development of OA cartilage lesions without inflammatory signs. The potencies of this biomaterial to protect OA joint should be further documented. It could then represent a new alternative for viscosupplementation in human OA management.

Bioreducible alginate-poly(ethylenimine) nanogels as an antigen-delivery system robustly enhance vaccine-elicited humoral and cellular immune responses.

Although polysaccharide nanogels have emerged as a novel antigen delivery system for vaccine development, whether modulating the redox sensitivity of nanogels could improve vaccine efficacy remains unclear. In the present study, we generated bioreducible cationic alginate-polyethylenimine (PEI) nanogels as a novel vaccine delivery system. Briefly, nanogels were prepared by the electrostatic interaction of negatively charged alginate sodium with branched PEI2k, followed by disulfide cross-linking to generate bioreducible nanogels (AP-SS). The AP-SS nanogels demonstrated great antigen-loading capacity and minimal cytotoxicity. The in vitro study showed that reducible AP-SS nanogels not only facilitated antigen uptake by mouse bone marrow dendritic cells (BMDCs), but also promoted intracellular antigen degradation and cytosolic release. Moreover, AP-SS nanogels significantly enhanced both MHC class I and II antigen presentation by BMDCs. Compared with the non-reducible nanogels, AP-SS nanogels more potently enhanced vaccine-induced antibody production and CD8+ T cell-mediated tumor cell lysis. Hence, the bioreducible alginate-PEI nanogels could serve as a potent adjuvant to improve vaccine-elicited humoral and cellular immune responses.

Alginate-coated chitosan nanogel capacity to modulate the effect of TLR ligands on blood dendritic cells.

Biodegradable nanoparticles have been employed for vaccine delivery, frequently admixed with adjuvants. Surprisingly, there is little information on their modulation of immune responses, speculated to be negligible. We analyzed the immunomodulatory capacity of alginate-coated chitosan nanogels (Ng), on porcine and human blood dendritic cells (DCs), when applied with defined adjuvants targeting different DC subpopulations. DC maturation, cytokine production and cell migration were assessed. Ng differentially influenced the immunomodulatory characteristics of individual Toll-like receptor (TLR) ligands: Pam3Cys-SK4-induced IL-1ß was enhanced; CpG-oligodeoxynucleotides (CpG-ODN)-induced IFN-α, IL-6 and TNFα were impaired; CpG-ODN-induced CD86 and CCR7, and cell migration, were diminished-plasmacytoid DCs (pDCs) were particularly sensitive. Therein, the Ng influence on DC endocytosis of the TLR ligands was apparently a major contributory element. This demonstrates the importance of predefining the interplay between delivery vehicles and admixed immunostimulatory moieties, for ensuring appropriate immune activation and efficacious combinations. FROM THE CLINICAL EDITOR: Biodegradable nanoparticles have been utilized in vaccine delivery; however, there is little information available on their immunomodulatory properties, which are thought to be negligible. This study clearly demonstrates that nanogels do influence the developing immune response, which needs to be taken into consideration when utilizing these otherwise very efficacious vaccine delivery approaches.

Review: efficacy of alginate supplementation in relation to appetite regulation and metabolic risk factors: evidence from animal and human studies.

This review provides a critical update on human and animal studies investigating the effect of alginate supplementation on appetite regulation, glycaemic and insulinemic responses, and lipid metabolism with discussion of the evidence on potential mechanisms, efficacy and tolerability. Dependent on vehicle applied for alginate supplementation, the majority of animal and human studies suggest that alginate consumption does suppress satiety and to some extent energy intake. Only one long-term intervention trial found effects on weight loss. In addition, alginates seem to exhibit beneficial influence on postprandial glucose absorption and insulin response in animals and humans. However, alginate supplementation was only found to have cholesterol-lowering properties in animals. Several mechanisms have been suggested for the positive effect observed, which involve delayed gastric emptying, increased viscosity of digesta and slowed nutrient absorption in the small intestine upon alginate gel formation. Despite reasonable efficacy and tolerability from the acute or short-term studies, we still realize there is a critical need for development of optimal alginate types and vehicles as well as studies on further long-term investigation on alginate supplementation in humans before inferring that it could be useful in the management of obesity and the metabolic syndrome.

Prilling for the development of multi-particulate colon drug delivery systems: pectin vs. pectin-alginate beads.

This paper proposes a multi-particulate drug delivery system produced by prilling technique in combination with an enteric coating. Optimization of process parameters, such as feed viscosity at nozzle, selection of cross-linker, pH of the gelling solution and cross-linking time, allows to obtain beads with strong gelled matrix. Results showed that dextran/piroxicam beads demonstrated high encapsulation efficiency, very narrow dimensional distribution and high sphericity. Coated beads retained shape and narrow size distribution of the uncoated particles. Moreover, the strength of the produced Zn(2+)-pectinate beads allows to reduce Eudragit coating thickness. Piroxicam loaded multi-particulate systems show an interesting prolonged drug release in intestinal fluids. Hence, such platforms could be proposed for the treatment of inflammatory bowel diseases.