Significant progress in improving Atorvastatin dissolution rate: Physicochemical characterization and stability assessment of self-dispersible Atorvastatin/Tween 80® nanocrystals formulated through wet milling and freeze-drying.

Atorvastatin (ATV) is a first-line drug for the treatment of hyperlipidemia. This drug presents biopharmaceutical problems, partly due to its low solubility and dissolution rate. In this work, nanocrystals of ATV stabilized with Tween 80® were designed by wet milling. A full factorial design was applied to optimize the process. Additionally, a cryoprotectant agent (maltodextrin, MTX) was identified, which allowed maintaining the properties of the nanocrystals after lyophilization. The storage stability of the nanocrystals was demonstrated for six months in different conditions. The obtained nanocrystal powder was characterized using SEM, EDXS, TEM, DSC, TGA, FT-IR, and XRD, showing the presence of irregular crystals with semi-amorphous characteristics, likely due to the particle collision process. Based on the reduction in particle size and the decrease in drug crystallinity, a significant increase in water and phosphate buffer (pH 6.8) solubility by 4 and 6 times, respectively, was observed. On the other hand, a noticeable increase in the dissolution rate was observed, with 90 % of the drug dissolved within 60 min of study, compared to 30 % of the drug dissolved within 12 h in the case of the untreated drug or the physical mixture of components. Based on these results, it can be concluded that the nano-milling of Atorvastatin stabilized with Tween 80® is a promising strategy for developing new formulations with improved biopharmaceutical properties of this widely used drug.

Formulation and optimization of pH-sensitive nanocrystals for improved oral delivery.

The challenge of low water solubility in pharmaceutical science profoundly impacts drug absorption and therapeutic effectiveness. Nanocrystals (NC), consisting of drug molecules and stabilizing agents, offer a promising solution to enhance solubility and control release rates. In the pharmaceutical industry, top-down techniques are favored for their flexibility and cost-effectiveness. However, increased solubility can lead to premature drug dissolution in the stomach, which is problematic due to the acidic pH or enzymes. Researchers are exploring encapsulating agents that facilitate drug release at customized pH levels as a valuable strategy to address this. This study employed wet milling and spray drying techniques to create encapsulated NC for delivering the drug to the intestinal tract using the model drug ivermectin (IVM). Nanosuspensions (NS) were efficiently produced within 2 h using NanoDisp®, with a particle size of 198.4 ± 0.6 nm and a low polydispersity index (PDI) of 0.184, ensuring uniformity. Stability tests over 100 days at 4 °C and 25 °C demonstrated practical viability, with no precipitation or significant changes observed. Cytotoxicity evaluations indicated less harm to Caco-2 cells compared to the pure drug. Furthermore, the solubility of the NC increased by 47-fold in water and 4.8-fold in simulated intestinal fluid compared to the pure active compound. Finally, dissolution tests showed less than 10% release in acidic conditions and significant improvement in simulated intestinal conditions, promising enhanced drug solubility and bioavailability. This addresses a long-standing pharmaceutical challenge in a cost-effective and scalable manner.

Application of 20% silver nanoclusters in polymethacrylic acid on simulated dentin caries; its penetration depth and effect on surface hardness.

The aims of this study were: To evaluate the surface hardness of simulated dentin caries lesions treated with either silver nanoclusters (AgNCls) synthesized in polymethacrylic acid (PMAA) or 38% silver diammine fluoride (SDF), as well as observe the penetration of the treatment solutions into the simulated caries lesions. Dentin blocks 4 mm thick obtained from caries-free third molars were sectioned and then simulated caries lesions on the occlusal dentin surfaces were created. Each specimen (n = 8) was divided into four sections: (A) treated with 20% AgNCls/PMAA; (B) treated with SDF 38% (FAgamin, Tedequim, Cordoba, Argentina); (C) sound tooth protected by nail-varnish during artificial caries generation (positive control); and (D) artificial caries lesion without surface treatment (negative control). AgNCls/PMAA or SDF were applied on the simulated lesions with a microbrush for 10 s, then excess removed. The surface hardness was measured by means of Vickers indentation test. To trace the depth of penetration, up to 400 µm, of silver ions, elemental composition of the samples was observed using EDX, coupled with SEM, and measured every 50 µm from the surface towards the pulp chamber. Laser Induced Breakdown Spectroscopy (LIBS) was also employed to trace silver ion penetration; the atomic silver line 328.06 nm was used with a 60 µm laser spot size to a depth of 240 µm. Student's-t test identified significant differences between treatment groups for each depth and the Bonferroni test was used for statistical analysis of all groups (p < 0.05). Mean surface hardness values obtained were 111.2 MPa, 72.3 MPa, 103.3 MPa and 50.5 MPa for groups A, B, C and D respectively. There was a significant difference between groups A and C compared with groups B and D, the group treated with AgNCls/PMAA achieved the highest surface hardness, similar or higher than the sound dentin control. A constant presence of silver was observed throughout the depth of the sample for group A, while group B showed a peak concentration of silver at the surface with a significant drop beyond 50 µm. The 20% AgNCls/PMAA solution applied to simulated dentin caries lesions achieved the recovery of surface hardness equivalent to sound dentin with the penetration of silver ions throughout the depth of the lesion.

Enhancing the Functional Properties of Tea Tree Oil: In Vitro Antimicrobial Activity and Microencapsulation Strategy.

In the context of addressing antimicrobial drug resistance in periocular infections, Tea Tree Oil (TTO) has emerged as a promising therapeutic option. This study aimed to assess the efficacy of TTO against bacterial strains isolated from ocular infections, with a particular focus on its ability to inhibit biofilm formation. Additionally, we designed and analyzed microcapsules containing TTO to overcome certain unfavorable physicochemical properties and enhance its inherent biological attributes. The quality of TTO was confirmed through rigorous analysis using GC-MS and UV-Vis techniques. Our agar diffusion assay demonstrated the effectiveness of Tea Tree Oil (TTO) against ocular bacterial strains, including Corynebacterium spp., coagulase-negative Staphylococcus spp., and Staphylococcus aureus, as well as a reference strain of Staphylococcus aureus (ATCC 25923). Notably, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for all tested microorganisms were found to be 0.2% and 0.4%, respectively, with the exception of Corynebacterium spp., which exhibited resistance to TTO. Furthermore, TTO exhibited a substantial reduction in biofilm biomass, ranging from 30% to 70%, as determined by the MTT method. Through the spray-drying technique, we successfully prepared two TTO-containing formulations with high encapsulation yields (80-85%), microencapsulation efficiency (90-95%), and embedding rates (approximately 40%). These formulations yielded microcapsules with diameters of 6-12 µm, as determined by laser scattering particle size distribution analysis, and exhibited regular, spherical morphologies under scanning electron microscopy. Importantly, UV-Vis analysis post-encapsulation confirmed the presence of TTO within the capsules, with preserved antioxidant and antimicrobial activities. In summary, our findings underscore the substantial therapeutic potential of TTO and its microcapsules for treating ocular infections.

3D-Printed Gastroretentive Tablets Loaded with Niclosamide Nanocrystals by the Melting Solidification Printing Process (MESO-PP).

Niclosamide (NICLO) is a recognized antiparasitic drug being repositioned for Helicobacter pylori. The present work aimed to formulate NICLO nanocrystals (NICLO-NCRs) to produce a higher dissolution rate of the active ingredient and to incorporate these nanosystems into a floating solid dosage form to release them into the stomach slowly. For this purpose, NICLO-NCRs were produced by wet-milling and included in a floating Gelucire l3D printed tablet by semi-solid extrusion, applying the Melting solidification printing process (MESO-PP) methodology. The results obtained in TGA, DSC, XRD and FT-IR analysis showed no physicochemical interactions or modifications in the crystallinity of NICLO-NCR after inclusion in Gelucire 50/13 ink. This method allowed the incorporation of NICLO-NCRs in a concentration of up to 25% w/w. It achieved a controlled release of NCRs in a simulated gastric medium. Moreover, the presence of NICLO-NCRs after redispersion of the printlets was observed by STEM. Additionally, no effects on the cell viability of the NCRs were demonstrated in the GES-1 cell line. Finally, gastroretention was demonstrated for 180 min in dogs. These findings show the potential of the MESO-PP technique in obtaining slow-release gastro-retentive oral solid dosage forms loaded with nanocrystals of a poorly soluble drug, an ideal system for treating gastric pathologies such as H. pylori.

Design and Development of Sublingual Printlets Containing Domperidone Nanocrystals Using 3D Melting Solidification Printing Process (MESO-PP).

Domperidone (DOM) is a drug commonly used to treat nausea and vomiting, as well as gastrointestinal disorders. However, its low solubility and extensive metabolism pose significant administration challenges. In this study, we aimed to improve DOM solubility and avoid its metabolism by developing nanocrystals (NC) of DOM through a 3D printing technology-melting solidification printing process (MESO-PP)-to be delivered via a solid dosage form (SDF) that can be administered sublingually. We obtained DOM-NCs using the wet milling process and designed an ultra-rapid release ink (composed of PEG 1500, propylene glycol, sodium starch glycolate, croscarmellose sodium, and sodium citrate) for the 3D printing process. The results demonstrated an increase in the saturation solubility of DOM in both water and simulated saliva without any physicochemical changes in the ink as observed by DSC, TGA, DRX, and FT-IR. The combination of nanotechnology and 3D printing technology enabled us to produce a rapidly disintegrating SDF with an improved drug-release profile. This study demonstrates the potential of developing sublingual dosage forms for drugs with low aqueous solubility using nanotechnology and 3D printing technology, providing a feasible solution to the challenges associated with the administration of drugs with low solubility and extensive metabolism in pharmacology.

Patterns of pharmaceutical supplies and medicines donations received during a natural disaster.

BACKGROUND: In response to emergencies, such as wildfires, donations of pharmaceuticals often occur. These donations can be given directly by governments, to non-governmental organizations as corporate donations, or by private entities that donate to individual health institutions. OBJECTIVE: This paper aimed to collect, review and analyze pharmaceutical product donations received during the natural disaster caused by wildfires in the San Luis province, Argentina, in September and October 2020. METHODS: A descriptive, cross-sectional, and retrospective study was performed. An introductory approach to good donation practices was also carried out. Medicines were classified and in the case of products that were not suitable for administration, these were discarded. RESULTS: A total of 15,593 units were segregated, of which 52.8% were over-the-counter products and 47.2% were prescription drugs. 86.3% (13,467 units) were accepted, while 13.7% (2126 units) had to be destroyed. The value of donations totaled USD 16,544. The analysis of the results showed that an important part of the donations was irrelevant in the emergency context. Donations were also received in incorrect amounts, which generated a large stock of medicines that couldn't be used. In emergencies, inappropriate donations create additional work during sorting, storage, and distribution, increasing the time professionals need to complete tasks. This extra work can easily overwhelm limited human and logistical resources. CONCLUSIONS: It is important to previously evaluate the real need for donations. In addition, the distribution of donations must be done through pre-established systems and policies. Otherwise, unsolicited and unnecessary drug donations become wasteful and should therefore be avoided.

Development of Triamcinolone Acetonide Nanocrystals for Ocular Administration.

Triamcinolone acetonide (TA) is a powerful anti-inflammatory drug used in the treatment of inflammatory ocular disorders; however, its poor aqueous solubility and ocular anatomical barriers hinder optimal treatment. The aim of this work was to obtain triamcinolone acetonide nanocrystals (TA-NC) to improve ocular corticosteroid therapy. Self-dispersible TA-NC were prepared by the bead milling technique followed by spray-drying, exhaustively characterized and then evaluated in vivo in an ocular model of endotoxin-induced uveitis (EIU). Self-dispersible TA-NC presented an average particle size of 257 ± 30 nm, a narrow size distribution and a zeta potential of -25 ± 3 mV, which remained unchanged for 120 days under storage conditions at 25 °C. In addition, SEM studies of the TA-NC showed uniform and spherical morphology, and FTIR and XRDP analyses indicated no apparent chemical and crystallinity changes. The subconjunctival administration of TA-NC in albino male white rabbits showed no clinical signs of ocular damage. In vivo studies proved that treatment with self-dispersible TA-NC alleviated the inflammatory response in the anterior chamber and iris in EUI rabbit eyes. Dispersible TA-NC are a promising approach to obtaining a novel nanometric TA formulation for ocular disorders.

Color changes and shear bond strength to simulated caries lesions treated with a novel solution of 20% silver nanoclusters in polymethacrylic acid.

The aims of the study were: (1) To compare the staining effect on demineralized dentin simulating caries between silver nanoclusters (AgNCls) synthesized using polymethacrylic acid (PMAA) and silver diammine fluoride (SDF), and (2) to measure the shear bond strength (SBS) of a glass ionomer cement (GIC) to simulated caries lesions with and without the application of AgNCls/PMAA or SDF. Dentine blocks 4 mm thick from twenty-four non-carious third molars were sectioned and coated with nail varnish (Revlon, New York, USA). Simulated caries lesions on occlusal dentin surfaces were created (66 h in 0.05 M acetate buffer 2.2 mM calcium/phosphate pH 5.0). Specimens were divided into groups and treated with (n = 8): (A) 20% AgNCls/PMAA; (B) SDF 38% (Fagamin, Tedequim, Córdoba, Argentina); or (C) without treatment. AgNCls/PMAA or SDF were applied on the exposed surfaces with a microbrush for 10 s. Samples were incubated for 24 h at 37 °C at 100% relative humidity. Surface color was measured according to the CIE-L*a*b* system before and after demineralization (R0 and R1), 24 h and one week after treatment (R2 and R3), using a spectrophotometer (CM-600D Konica Minolta Sesing Inc., Japan). Groups A and B received an extra application of AgNCls/PMAA or SDF before a conventional GIC (Fuji IX-Gold Label, GC Corp, Tokyo, Japan) was bonded using a mold, 4 mm diameter × 3 mm high. For SBS, a Universal Testing Machine (Digimess RS-8000-5, China)-crosshead speed of 1 mm/min-was used. Statistical analysis was performed using ANOVA, Student-t and Scheffe-test at a significance of p < 0.05. Group A presented a stable color p = 0.24 between R1-R2 and R1-R3 in contrast to significant color changes in Group B (p = 0.02). SBS was higher (p < 0.01) in Group A (10.4 ± 2.7 MPa) compared to Groups B (3.3 ± 1.3 MPa) and C (4.0 ± 0.4 MPa), where no differences between the latter groups were observed (p = 0.77). Results of this preliminary study demonstrated that 20% AgNCls/PMAA did not stain simulated carious dentin and improved SBS of the GIC. The relevance of this study relies on the development of a therapeutic system to potentially arrest caries lesions without staining.

Mathematical and Pharmacokinetic Approaches for the Design of New 3D Printing Inks Using Ricobendazole.

PURPOSE: 3D printing (3DP) makes it possible to obtain systems that are not achievable with current conventional methods, one of them, sustained release floating systems. Floating systems using ricobendazole (RBZ) as a model drug and a combination of polymers were designed and obtained by melt solidification printing technique (MESO-PP). METHODS: Four different MESO-PP inks were formulated based on combinations of the polymers Gelucire 43/01 and Gelucire 50/13 in different ratios. For each of the formulated inks, physicochemical characterization was performed by thermal analysis (thermogravimetric analysis [TGA] and differential scanning calorimetry [DSC]), fourier transform infrared spectrophotometer (FTIR) and X-ray diffraction (XRD). Pharmaceutical characterization was performed by in vitro assays to determine pharmaceutically relevant parameters. These parameters were calculated by applying mathematical models developed to evaluate in vitro drug release profiles. On the other hand, a physiologically based pharmacokinetic (PBPK) model was developed to predict the in vivo performance of RBZ loaded in the different inks by determining the Cmax, and the AUC0-∞. RESULTS: By increasing the proportion of Gelucire 50/13 co-surfactant in the mixtures (the proportion in Ink 1 was 33%, while the proportion in Ink 4 was 80%), the dissolution capacity of RBZ increases substantially, decreasing flotation times. CONCLUSION: MESO-PP produced ink 1 (50% Gelucire 43/01, 25% Gelucire 50/13 and 25% RBZ), which has a zero-order release (RR = 0.180%/min) and the longest flotation time (545 ± 23 min), and in turn would produce a significant increase in oral absorption of the drug, with an AUC0-∞ 2.16-fold higher than that obtained in animals treated with RBZ loaded in conventional tablets.

Spray-drying-microencapsulated Minthostachys verticillata essential oil and limonene as innovative adjuvant strategy to bovine mastitis vaccines.

Design of innovative adjuvant strategies with an appropriate safety profile is relevant to developed subunit or inactivated microorganism vaccines for bovine mastitis. Minthostachys verticillata essential oil (EO) has demonstrated ability to stimulate the innate immune response and adjuvant effect similar to Al(OH)3. Here we evaluated the adjuvant effect of EO and its metabolite, limonene (L) alone and microencapsulated by spray-drying, using an inactivated Enterococcus faecium strain bovine-mastitis inducer. The gas chromatography-mass spectrometry analysis showed that microencapsulation process did not alter the EO or L chemistry. Microencapsulated EO (McEO) or L (McL) (2.0, 2.5 and 5.0 mg/ml) decreased the viability of bovine mammary gland epithelial cells in a dose-dependent way. Balb/c mice (n = 32) were subcutaneously inoculated (day 0) and revaccinated (day 14 and 28) with saline solution, inactivated bacteria alone or combined with Incomplete Freund's Adjuvant; EO or L (2.5 mg/ml); McEO or McL (5.0 mg/ml); or microcapsule wall material (Mc) alone (2.5 mg/ml). EO, L, McEO and McL stimulated E. faecium-specific IgG (IgG1 or IgG2a) with opsonizing capacity and increased the proportion of CD4+ and CD8+ T cells producers of IFN-γ. Microencapsulation was an effective strategy to increase the adjuvant potential of EO or L. These new adjuvants deserve further study to evaluate their incorporation into vaccines for bovine mastitis.

Nanocrystal-based 3D-printed tablets: Semi-solid extrusion using melting solidification printing process (MESO-PP) for oral administration of poorly soluble drugs.

This is the first report on the inclusion of nanocrystals (NCs) within 3D-printed oral solid dosage forms -3D-printed tablets or printlets- produced by the Melting Solidification Printing Process (MESO-PP) 3D printing technique. This method allowed the incorporation of albendazole (ABZ) nanocrystals in a concentration of up to 50% w/w, something not achieved in conventional tablets. An ink of PEG 1500/propylenegycol was used as a carrier and no physicochemical interactions or crystallinity modifications were observed due to the inclusion of ABZ-NCs into the ink, as demonstrated by TGA, DSC, XRD and FT-IR. In particular, the relative crystallinity of the ink loaded with NCs was 97.8% similar to the physical mixture of the components. Moreover, the presence of NCs was observed in the surface and matrix of the printlets by SEM. In addition, the printlet NCs demonstrated to be more effective than NCs included in hard gelatin capsules in improving drug dissolution in HCl 0.1 N. The particle size, crystallinity and chemical stability of the nanocrystals was maintained before and after 180 days of storage. Thus, these findings exhibit relevant pharmaceutical potential for developing stable, fast-release, oral, solid dosage forms of poorly soluble drugs combining 3D printing and nanocrystals. Additionally, this technique could be applied for printing objects using different types of nanocrystals embedded in low melting temperature polymers.

Albendazole Nanocrystal-Based Dissolving Microneedles with Improved Pharmacokinetic Performance for Enhanced Treatment of Cystic Echinococcosis.

Cystic echinococcosis (CE) is a zoonosis caused by Echinococcus spp., affecting both humans and animals' lives. Current treatment of CE by oral administration of albendazole (ABZ) is hampered by several limitations. The poor aqueous solubility and the rapid metabolism of ABZ in the liver are the main issues, leading to lack of efficacy of the treatment. In the present study, we developed a nanocrystalline (NC) formulation of ABZ to be delivered intradermally using dissolving microneedles (DMNs). The NC formulation was developed using milling in an ultrasmall-scale device. Following several screenings, Pluronic F127 was selected as a suitable stabilizer, producing NCs with around 400 nm in size with narrow particle distribution. The crystallinity of ABZ was maintained as observed by DSC and XRD analysis. The NC approach was able to improve the dissolution percentage of ABZ by approximately three-fold. Furthermore, the incorporation of NCs into DMNs using the combination of poly(vinylpyrrolidone) and poly(vinyl alcohol) formed sharp needles with sufficient mechanical strength and insertion properties. Dermatokinetic studies revealed that >25% of ABZ was localized in the dermis of excised neonatal porcine skin up to 48 h after DMN administration. In in vivo pharmacokinetic studies, the AUC and relative bioavailability values of ABZ delivered by NC-loaded DMNs were found to be significantly higher than those obtained after oral administration of coarse suspension of ABZ or ABZ-NCs, as well as DMNs delivering coarse ABZ as indicated by the relative bioavailability values of >100%. Therefore, the combination approach developed in this study could maintain the systemic circulation of ABZ, which could be possibly caused by avoiding the first-pass metabolism in the liver. This could be beneficial to improve the efficacy of ABZ in CE treatment.

Polymeric antigen BLSOmp31 formulated with class B CpG-ODN in a nanostructure (BLSOmp31/CpG-ODN/Coa-ASC16) administered by parenteral or mucosal routes confers protection against Brucella ovis in Balb/c mice.

Previously, we demonstrated that the chimera BLSOmp31 formulated in chitosan microspheres or Poloxamer407-Chitosan administered via the nasal and the ocular mucosa conferred partial protection in sheep against B. ovis. In this work, we tested a new delivery system for mucosal immunization with BLSOmp31 in the murine model to improve the efficacy of previously used formulations. First, we evaluated the protective efficacy against B. ovis induced by BLSOmp31 administered by the subcutaneous route using either BLSOmp31 alone, co-administered with immunostimulatory synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG-ODN) or with CpG-ODN in a nanostructure called Coa-ASC16 compared with BLSOmp31 emulsified in Incomplete Freund Adjuvant. Then, we evaluated the protection conferred by the best performing formulation (BLSOmp31/CpG-ODN/Coa-ASC16) administered by both subcutaneous and ocular routes. BLSOmp31/CpG-ODN/Coa-ASC16 injected subcutaneously did not induce higher IgG antibody levels compared to BLSOmp31 alone or BLSOmp31/CpG-ODN but it did stimulate a mixed immune Th1-Th2 response with the highest levels of IFN-É£ and conferred significant protection against the B. ovis challenge. Although ocular instillation of BLSOmp31/CpG-ODN/Coa-ASC16 showed a similar degree of protection compared to the parenteral route (3.66 and 3.60 logs of protection, respectively), it induced lower levels in serum of specific IgG (with mixed IgG1/IgG2a) and IgA antibodies and, less IFN-É£ and IL-4 than the subcutaneous route. No antibodies were detected in vaginal lavages or saliva. Fecal antigen-specific IgA was slightly higher in mice immunized with BLSOmp31/CpG-ODN/Coa-ASC16 subcutaneously compared with the ocular route. These results indicate that BLSOmp31/CpG-ODN/Coa-ASC16 was a safe and effective vaccine against B. ovis in mice.

Novel hybrid lipid nanocapsules loaded with a therapeutic monoclonal antibody - Bevacizumab - and Triamcinolone acetonide for combined therapy in neovascular ocular pathologies.

The aim of this study was to design and develop a novel hybrid formulation based on lipid nanocapsules containing bevacizumab (BVZ), an effective therapeutic antibody, on the surface and triamcinolone acetonide (TA) in the inner core (BVZ-TA-LNC) intended to improve ocular therapy. Hence, a phase inversion-insertion one step method was developed to drug loading and surface modification of lipid nanocapsules by post-insertion of a bifunctional polymer, followed by antibody coupling using "click" chemistry. The covalent bond and antibody capacity binding to its specific antigen were confirmed by thermal analysis and immunoassay, respectively. BVZ-TA-LNC presented nanometric size (102 nm), negative surface potential (-19 mV) and exhibiting 56% of TA in the lipid core. BVZ-TA-LNC tended to prevent the endothelial cell migration and significantly prevented the capillary formation induced by the vascular endothelium growth factor (VEGF). The novel hybrid system allowed the co-loading of two different therapeutic molecules and may be promising to improve the therapy of eye disorders that occur with inflammation and/or neovascularization.

A Vaccine Based on Kunitz-Type Molecule Confers Protection Against Fasciola hepatica Challenge by Inducing IFN-γ and Antibody Immune Responses Through IL-17A Production.

Fasciola hepatica is helminth parasite found around the world that causes fasciolosis, a chronic disease affecting mainly cattle, sheep, and occasionally humans. Triclabendazole is the drug of choice to treat this parasite. However, the continuous use of this drug has led to the development of parasite resistance and, consequently, the limitation of its effectiveness. Hence, vaccination appears as an attractive option to develop. In this work, we evaluated the potential of F. hepatica Kunitz-type molecule (FhKTM) as an antigen formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate ester (Coa-ASC16) and the synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) during an experimental model of fasciolosis in mice, and we further dissected the immune response associated with host protection. Our results showed that immunization of mice with FhKTM/CpG-ODN/Coa-ASC16 induces protection against F. hepatica challenge by preventing liver damage and improving survival after F. hepatica infection. FhKTM/CpG-ODN/Coa-ASC16-immunized mice elicited potent IFN-γ and IL-17A with high levels of antigen-specific IgG1, IgG2a, and IgA serum antibodies. Strikingly, IL-17A blockade during infection decreased IgG2a and IgA antibody levels as well as IFN-γ production, leading to an increase in mortality of vaccinated mice. The present study highlights the potential of a new vaccine formulation to improve control and help the eradication of F. hepatica infection, with potential applications for natural hosts such as cattle and sheep.

High Dose Of Ascorbic Acid Used In Sars Covid-19 Treatment: Scientific And Clinical Support For Its Therapeutic Implementation / Utilización de altas dosis de ácido ascórbico en el tratamiento del SARS Covid-19: Soporte Científico y Clínico para su aplicación en terapéutica

El coronavirus 2019 (SARS-CoV-2) ha sido declarado una emergencia de salud pública de impacto internacional por la Organización Mundial de la Salud. Debido a la aparición repentina de este proceso pandémico asociado con alta morbilidad y la mortalidad en todo el mundo, se han implementado varios tratamientos en los pacientes aquejados con esta dolencia. En este marco, comenzaron a usarse en pacientes críticos altas dosis de vitamina C. En este trabajo, analizamos los ensayos clínicos y / o trabajos de investigación disponibles en la literatura. Aunque se necesita más evidencia sobre su efectividad, es importante que el especialista comprenda la lógica clínica de este uso para determinar si es correcto como tratamiento concomitante. Conclusiones: El uso de altas dosis de vitamina C por vía parenteral parece ser una alternativa segura, disponible y económica, especialmente para pacientes críticos

The 2019 coronavirus (SARS-CoV-2) has been declared a public health emergency of international concern by the World Health Organization. Due to the sudden appearance of this pandemic process associated with increasing morbidity and mortality worldwide, various treatments have been implemented. In this framework, high doses of vitamin C began to be used in critically ill patients. We analyze the clinical trials and/or research papers available in the literature. Although more evidence on its effectiveness is needed is important for the specialist to understand the clinical logic of this use to determine if it is correct as a concomitant treatment. Conclusions: It seems that using high doses of vitamin C parenterally is a safe, available and economical alternative especially for critically ill patients

Albendazole solid dispersions against alveolar echinococcosis: a pharmacotechnical strategy to improve the efficacy of the drug.

Alveolar echinococcosis is a neglected parasitic zoonosis caused by Echinococcus multilocularis. The pharmacological treatment is based on albendazole (ABZ). However, the low water solubility of the drug produces a limited dissolution rate, with the consequent failure in the treatment of the disease. Solid dispersions are a successful pharmacotechnical strategy to improve the dissolution profile of poorly water-soluble drugs. The aim of this work was to determine the in vivo efficacy of ABZ solid dispersions using poloxamer 407 as a carrier (ABZ:P407 solid dispersions (SDs)) in the murine intraperitoneal infection model for secondary alveolar echinococcosis. In the chemoprophylactic efficacy study, the ABZ suspension, the ABZ:P407 SDs and the physical mixture of ABZ and poloxamer 407 showed a tendency to decrease the development of murine cysts, causing damage to the germinal layer. In the clinical efficacy study, the ABZ:P407 SDs produced a significant decrease in the weight of murine cysts. In addition, the SDs produced extensive damage to the germinal layer. The increase in the efficacy of ABZ could be due to the improvement of water solubility and wettability of the drug due to the surfactant nature of poloxamer 407. In conclusion, this study is the basis for further research. This pharmacotechnical strategy might in the future offer novel treatment alternatives for human alveolar echinococcosis.

Development of solid self-emulsifying drug delivery systems (SEDDS) to improve the solubility of resveratrol.

Aim: A solid self-emulsifying drug delivery systems was developed by using the spray-drying technique, to improve the solubility of resveratrol (RES). Materials & methods: Cod liver oil and three surfactant system were tested: soy phosphatidylcholine (SPC)/Eumulgin® HRE-40 (EU)/Sodium oleate (system A); SPC/Tween®80 (TW) /Sodium oleate (system B) and SPC/EU/TW (system C). Results: The greatest incorporation was obtained with system C (21.26 mg/ml). Solid self-emulsifying drug delivery systems with the highest yield were obtained with colloidal silicon dioxide (CSD) (80.12%), and CSD sodium croscarmelose 9:1 and 5:5. RES dissolution attained 100% at 45 min with CSD:CS 5:5. Discussion: The surface modification to hydrophilic by CSD:sodium croscarmellose reduced the cohesive force among drug particles. Conclusion: The developed systems are a good approximation for the design of strategies that could allow increasing the oral bioavailability of RES.

Antioxidant status in rabbit aqueous humor after instillation of ascorbyl laurate-based nanostructures.

BACKGROUND: The aim of this work was evaluate the antioxidant effect of ascorbyl laurate (ASC12) based nanostructures applied topically to the cornea of ocular normotensive and hypertensive rabbits. The ASC12 was chosen for its capacity to form liquid lyotropic crystal and keeps its free radical trapping power. METHODS: The hypertension model was performed in six rabbits and was obtained by the application of intracameral injections of alpha-chymotrypsin in the right eye. A single 50 ml dose of ascorbyl laurate coagel 2% w/v (COA-ASC12) was applied topically to the cornea of six normotensive and six hypertensive rabbits. The aqueous humor samples were obtained before and after instillation of COA-ASC12 at different times (2 h and 4 h). Antioxidant capacity was determined via the reduction reaction with iron and tripyridyltriazine (FRAP) and the total proteins were measured using the Bradford reagent. RESULTS: The kinetic antioxidant capacity in the aqueous humor of normotensive and hypertensive rabbits showed a maxim increment at 4 h instillation. Also, the antioxidant capacity in the aqueous humor of hypertensive rabbits was ten times lower than in normotensive rabbits. CONCLUSION: This type of nanostructures has the potential to significantly improve the topical formulation for the prophylaxis and treatment of several eye diseases.