A novel pH-responsive hydrogel-based on calcium alginate engineered by the previous formation of polyelectrolyte complexes (PECs) intended to vaginal administration.

This work aimed to develop a calcium alginate hydrogel as a pH responsive delivery system for polymyxin B (PMX) sustained-release through the vaginal route. Two samples of sodium alginate from different suppliers were characterized. The molecular weight and M/G ratio determined were, approximately, 107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer rheological investigations were further performed through the preparation of hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the acquisition of pseudoplastic viscous system able to acquiring a differential structure in simulated vaginal microenvironment (pH 4.5). The PMX-loaded hydrogel (hydrogel_PMX) was engineered based on polyelectrolyte complexes (PECs) formation between alginate and PMX followed by crosslinking with calcium chloride. This system exhibited a morphology with variable pore sizes, ranging from 100 to 200 µm and adequate syringeability. The hydrogel liquid uptake ability in an acid environment was minimized by the previous PECs formation. In vitro tests evidenced the hydrogels mucoadhesiveness. PMX release was pH-dependent and the system was able to sustain the release up to 6 days. A burst release was observed at pH 7.4 and drug release was driven by an anomalous transport, as determined by the Korsmeyer-Peppas model. At pH 4.5, drug release correlated with Weibull model and drug transport was driven by Fickian diffusion. The calcium alginate hydrogels engineered by the previous formation of PECs showed to be a promising platform for sustained release of cationic drugs through vaginal administration.

Impact of feed counterion addition and cyclone type on aerodynamic behavior of alginic-atenolol microparticles produced by spray drying.

The inhalatory route has emerged as an interesting non-invasive alternative for drug delivery. This allows both pulmonary (local) and systemic treatments (via alveolar absorption). Further advantages in terms of stability, dose and patient preference have often lead researchers to focus on dry powder inhaler delivery systems. Atenolol is an antihypertensive drug with low oral bioavailability and gastrointestinal side effects. Because atenolol possesses adequate permeation across human epithelial membranes, it has been proposed as a good candidate for inhalatory administration. In a previous work, atenolol was combined with alginic acid (AA) and microparticles were developed using spray-drying (SD) technology. Different AA/atenolol ratios, total feed solid content and operative variables were previously explored. In order to improve particle quality for inhalatory administration and the SD yield, in this work the AA acid groups not neutralized by atenolol were kept either free or neutralized to pH∼7 and two different SD cyclones were used. Particle morphology, flow properties, moisture uptake and in vitro aerosolization behavior at different pressure drops were studied. When the AA acid groups were neutralized, particle size decreased as a consequence of the lower feed viscosity. The SD yield and in vitro particle deposition significantly increased when a high performance cyclone was employed, and even when lactose carrier particles were not used. Although the in vitro particle deposition decreased when the storage relative humidity increased, the developed SD powders showed adequate characteristics to be administered by inhalatory route up to storage relative humidities of about 60%.

Injectable alginate hydrogel for enhanced spatiotemporal control of lentivector delivery in murine skeletal muscle.

Hydrogels are an especially appealing class of biomaterials for gene delivery vehicles as they can be introduced into the body with minimally invasive procedures and are often applied in tissue engineering and regenerative medicine strategies. In this study, we show for the first time the use of an injectable alginate hydrogel for controlled delivery of lentivectors in the skeletal muscle of murine hindlimb. We propose to alter the release rates of lentivectors through manipulation of the molecular weight distribution of alginate hydrogels. The release of lentivector was tested using two different ratios of low and high molecular weight (MW) alginate polymers (75/25 and 25/75 low/high MW). The interdependency of lentivector release rate and alginate degradation rate was assessed in vitro. Lentivector-loaded hydrogels maintained transduction potential for up to one week in vitro as demonstrated by the continual transduction of HEK-293T cells. Injection of lentivector-loaded hydrogel in vivo led to a sustained level of transgene expression for more than two months while minimizing the copies of lentivirus genome inserted into the genome of murine skeletal muscle cells. This strategy of spatiotemporal control of lentivector delivery from alginate hydrogels may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine.

A new strategy based on SmRho protein loaded chitosan nanoparticles as a candidate oral vaccine against schistosomiasis.

BACKGROUND: Schistosomiasis is one of the most important neglected tropical diseases and an effective control is unlikely in the absence of improved sanitation and vaccination. A new approach of oral vaccination with alginate coated chitosan nanoparticles appears interesting because their great stability and the ease of target accessibility, besides of chitosan and alginate immunostimulatory properties. Here we propose a candidate vaccine based on the combination of chitosan-based nanoparticles containing the antigen SmRho and coated with sodium alginate. METHODS AND FINDINGS: Our results showed an efficient performance of protein loading of nanoparticles before and after coating with alginate. Characterization of the resulting nanoparticles reported a size around 430 nm and a negative zeta potential. In vitro release studies of protein showed great stability of coated nanoparticles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Further in vivo studies was performed with different formulations of chitosan nanoparticles and it showed that oral immunization was not able to induce high levels of antibodies, otherwise intramuscular immunization induced high levels of both subtypes IgG1 and IgG2a SmRho specific antibodies. Mice immunized with nanoparticles associated to CpG showed significant modulation of granuloma reaction. Mice from all groups immunized orally with nanoparticles presented significant levels of protection against infection challenge with S. mansoni worms, suggesting an important role of chitosan in inducing a protective immune response. Finally, mice immunized with nanoparticles associated with the antigen SmRho plus CpG had 38% of the granuloma area reduced and also presented 48% of protection against of S. mansoni infection. CONCLUSIONS: Taken together, this results support this new strategy as an efficient delivery system and a potential vaccine against schistosomiasis.

Clinical trial comparing 3 different wound dressings for the management of partial-thickness skin graft donor sites.

PURPOSE: A review of the literature reveals a lack of consensus regarding local management of skin graft donor sites. This study was undertaken to determine the effects of 3 different dressings on healing of donor sites and patient discomfort related to donor sites. DESIGN: This study is a comparison cohort study. SUBJECTS AND SETTING: We recruited 34 burn patients scheduled for partial-thickness skin grafts; their mean age was 36 ± 18 years (mean ± SD, range 20 to 54 years), and 63% were male. All subjects were managed at Burn Unity Care, located in Sao Paulo, Brazil. MATERIALS AND METHODS: Subjects were randomly allocated to 1 of 3 groups: (1) a study group (group A) whose donor sites were dressed with a bovine collagen calcium-alginate dressing covered with transparent polyurethane film; (2) a second intervention group (group B), whose donor sites were dressed only with transparent polyurethane film dressing; and (3) a control group whose donor sites were dressed with rayon soaked in 0.9% saline (group C). Two independent observers assessed donor site wounds for epithelialization, scabbing, quantity and characteristics of exudate, and complications. Pain was measured using the visual analog scale, the brief pain inventory, and Index of Pain Management. RESULTS: Subjects managed with the bovine collagen calcium-alginate dressing covered with transparent polyurethane film (group A) achieved the greatest epithelialization (6.3 vs 8.2 for thin film dressing only P < .02 and 6.3 vs 11.7 days for control group P < .01). Patients managed with the bovine collagen calcium-alginate dressing covered with transparent polyurethane film also reported less pain that subjects allocated to the control (group C) or thin film only group (group B), (P < .05). Ninety percent of subjects allocated to the calcium alginate covered with thin film dressing reported mild pain intensity on the Visual Analog Scale, 85% of did not report pain localized to the donor site on the brief pain inventory, and scores on the Index of Pain Management ranged from 23 to 11. CONCLUSION: Study findings suggest that use of a collagen calcium-alginate dressing with a transparent film covering reduces the time for complete epithelialization and may reduce pain related to skin graft donor sites.

[Acid suppression capacity of omeprazole, sodium bicarbonate and alginic acid in an oral powder combination]. / Capacidad acidosupresora de omeprazol, bicarbonato de sodio y alginato de sodio en polvo para suspensión oral.

BACKGROUND: The combination of omeprazole, sodium bicarbonate and alginic acid protects omeprazole from acid degradation and enhances the speed of action of the proton pump inhibitors. AIM: To assess acid suppression capacity and speed of action of an oral powder combination (omeprazole 20 mg, sodium bicarbonate 1680 mg and alginic acid 250.08 mg) in healthy subjects, using gastric 24 h pHmetry. SUBJECTS AND METHODS: Gastric 24 h pHmetry was performed in 13 healthy subjects on days 0 and 6. During the first pHmetry, 7 subjects received the combination 2 h before the end of the procedure. The second study was performed after the subjects had been administered the medication for the six previous days. The measurements were: a) time with pH < 4, b) time to reach maximum pH value, and c) pH peak after first drug administration. RESULTS: The percentage of time with pH < 4 was 72.02 +/- 20.18 in the first study and 34.05 +/- 20.50 in the second (p < 0.01). Maximum pH obtained after first drug administration was 6.98 +/- 1.66 and the time to reach the pH peak was 18.34 +/- 9.84 minutes. CONCLUSION: This oral powder combination induces significant, fast and intensive gastric acid suppression. Unlike delayed-release proton pump inhibitors, this product provides a faster but equally sustained control of gastric acidity.

Alginate- and gellan-based edible films for probiotic coatings on fresh-cut fruits.

Alginate- (2% w/v) or gellan-based (0.5%) edible films, containing glycerol (0.6% to 2.0%), N-acetylcysteine (1%), and/or ascorbic acid (1%) and citric acid (1%), were formulated and used to coat fresh-cut apple and papaya cylinders. Water vapor permeability (WVP) was significantly higher (P < 0.05) in alginate films (0.30 to 0.31 x 10(-9) g m/Pa s m2) than in the gellan ones (0.26 to 0.27 x 10(-9) g m/Pa s m2). Addition of 0.025% (w/v) sunflower oil decreased WVP of gellan films (0.20 to 0.22 x 10(-9) g m/Pa s m2). Water solubility of gellan and alginate films at 25 degrees C (0.47 to 0.59 and 0.74 to 0.79, respectively) and their swelling ratios (2.3 to 2.6 and 1.6 to 2.0, respectively) indicate their potential for coating high moisture fresh-cut fruits. Fresh-cut apple and papaya cylinders were successfully coated with 2% (w/v) alginate or gellan film-forming solutions containing viable bifidobacteria. WVP in alginate (6.31 and 5.52 x 10(-9) g m/Pa s m2) or gellan (3.65 and 4.89 x 10(-9) g m/Pa s m2) probiotic coatings of papaya and apple, respectively, were higher than in the corresponding cast films. The gellan coatings and films exhibited better water vapor properties in comparison with the alginate coatings. Values > 10(6) CFU/g B. lactis Bb-12 were maintained for 10 d during refrigerated storage of fresh-cut fruits, demonstrating the feasibility of alginate- and gellan-based edible coatings to carry and support viable probiotics on fresh-cut fruit.

Immunostimulation of white shrimp (Litopenaeus vannamei) following dietary administration of Ergosan.

Ergosan an algal product containing 1% alginic acid, developed for use in aquaculture and reported to have immunomodulatory activity, was administered orally to intermoult adult white shrimp (Litopenaeus vannamei) for 15 days. Examination of haemolymph proteins using SDS-PAGE did not reveal any obvious differences between control and Ergosan treated shrimp. Similarly, total haemocyte counts were found to be roughly equivalent for both the control and experimental samples. However, differential analysis of haemocyte populations revealed marked changes in terms of the relative levels of hyaline, semi-granular, and particularly granular haemocytes between the two groups. Moreover, enhancement of the in vitro antimicrobial activity of haemolymph towards two shrimp pathogenic Vibrio isolates was recorded for shrimp fed with Ergosan. Finally, shrimp fed with Ergosan showed a significant increase in relative growth when compared with control groups.