3D printed scaffolds as delivery devices for nanocrystals: A proof of concept loading Atorvastatin with enhanced properties for sublingual route of administration.

Increasing the solubility of drugs is a recurrent objective of pharmaceutical research, and one of the most widespread strategies today is the formulation of nanocrystals (NCs). Beyond the many advantages of formulating NCs, their incorporation into solid dosage forms remains a challenge that limits their use. In this work, we set out to load Atorvastatin NCs (ATV-NCs) in a delivery device by combining 3D scaffolds with an "in situ" loading method such as freeze-drying. When comparing two infill patterns for the scaffolds at two different percentages, the one with the highest NCs load was chosen (Gyroid 20 % infill pattern, 13.8 ± 0.5 mg). Colloidal stability studies of NCs suggest instability in acidic media, and therefore, the system is postulated for use as a sublingual device, potentially bypassing stomach and hepatic first-pass effects. An ad hoc dissolution device was developed to mimic the release of actives. The nanometric size and properties acquired in the process were maintained, mainly in the dissolution rate and speed, achieving 100 % dissolution of the content in 180 s. Based on these results, the proof of concept represents an innovative approach to converting NCs suspensions into solid dosage forms.

Improved biodistribution and enhanced immune response of subunit vaccine using a nanostructure formed by self-assembly of ascorbyl palmitate.

New adjuvant strategies are needed to improve protein-based subunit vaccine immunogenicity. We examined the potential to use nanostructure of 6-O-ascorbyl palmitate to formulate ovalbumin (OVA) protein and an oligodeoxynucleotide (CpG-ODN) (OCC). In mice immunized with a single dose, OCC elicited an OVA-specific immune response superior to OVA/CpG-ODN solution (OC). Rheological studies demonstrated OCC's self-assembling viscoelastic properties. Biodistribution studies indicated that OCC prolonged OVA and CpG-ODN retention at injection site and lymph nodes, reducing systemic spread. Flow-cytometry assays demonstrated that OCC promoted OVA and CpG-ODN co-uptake by Ly6ChiCD11bhiCD11c+ monocytes. OCC and OC induced early IFN-γ in lymph nodes, but OCC led to higher concentration. Conversely, mice immunized with OC showed higher serum IFN-γ concentration compared to those immunized with OCC. In mice immunized with OCC, NK1.1+ cells were the IFN-γ major producers, and IFN-γ was essential for OVA-specific IgG2c switching. These findings illustrate how this nanostructure improves vaccine's response.

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.

Development of melatonin-loaded, human-serum-albumin nanoparticles formulations using different methods of preparation for ophthalmic administration.

The use of proteins such as human serum albumin (HSA) to form nanometric systems seems very promising since they are non-toxic, biodegradable and have no antigenic activity. This molecule is ideal to transport insoluble drugs such as melatonin (Mel), which has antiapoptotic and antioxidant properties and appears promising for the treatment of neurodegenerative eye diseases. The objective of this study was to obtain nanoparticulate systems loaded with Mel, improving the conventional desolvation method. Systems were stabilised using two different strategies: one through the use of Eudragit S100 as a cross-linking agent and the other through thermal stabilisation. The systems thus obtained (Np-HSA-Eu-Mel and Np-HSA-Mel, respectively) were characterised and compared in terms of physicochemical and pharmacotechnical parameters. Whitish colloidal dispersions of nanometric size (≈170 nm), spherical shape, and monodisperse population were obtained. Besides, the pH was close to neutrality reaching 20 % drug encapsulation whereas the process performance was higher than 80 %. In FT-IR studies, thermal analysis and X-ray diffraction (XRD), the incorporation of the drug in the cavities of the nanoparticles could be evidenced. Regarding the physical stability of nanoparticles, for Np-HSA-Eu-Mel instability was observed at pH > 7. However, Np-HSA-Mel was able to remain stable at different pH levels. Mel release from these systems was consequently affected, where the former released faster than the active compared to the last. On the other hand, it was observed that the drying process (lyophilization in this case) applied to the nanoparticles suspensions does not affect their original properties after redispersion over a three months period. Likewise, the formulation did not produce irritation when administered topically, whereas when administered subconjunctivally, only slight irritation was observed 24 h after administration. According to the result of this study, the Np-HSA-Mel formulation could achieve advantageous properties as a vehicle for the transport of insoluble drugs for the treatment of neurodegenerative diseases at the ocular level.

Eugenol carbonate activity against Plasmodium falciparum, Leishmania braziliensis, and Trypanosoma cruzi.

Neglected tropical diseases are a major health problem throughout the world, and there are few effective and safe drugs. In this study, we report the design and synthesis of a novel series of carbonates of eugenol using different aliphatic alcohols and N,N-carbonyldiimidazole. Spectroscopic techniques, including 1 H nuclear magnetic resonance (NMR), 13 C NMR, Fourier transform infrared, and high-resolution mass spectrometry, were used to confirm the structures of the synthesized compounds. In vitro and in silico studies of prodrugs of eugenol were performed to determine their antiplasmodial, trypanocidal, and leishmanicidal activities, and also their cytotoxicity. Compounds were highly active against Leishmania braziliensis and Plasmodium falciparum, whereas the activity shown for Trypanosoma cruzi was moderate. Molecular docking was used to determine a possible mode of action of eugenol against the dihydroorotate dehydrogenase of the three parasites (TcDHODH, LbDHODH, and PfDHODH). Notably, the docking results showed that eugenol not only has binding energy similar to that of the natural substrate (-7.2 and -7.1, respectively) but also has interactions with relevant biological residues of PfDHODH. This result indicates that eugenol could act as a substrate for PfDHODH in the pyrimidine biosynthesis pathway of P. falciparum. In conclusion, the combination of certain aliphatic alcohols and eugenol through a carbonate bond could significantly increase the antiparasitic activity of this class of compounds, which merits further studies.

COVID-19: Epidemiological Situation of Argentina and its Neighbor Countries after Three Months of Pandemic.

OBJECTIVE: In this work, in order to establish a better comprehension of the association between Argentina and its neighbor countries' capacity, and COVID-19 burden during the first 3 months, different indicators were evaluated. METHOD: We analyzed the association between GHSI, INFORM index and COVID-19 burden (number of confirmed cases and deaths), also the number of tests, lethality and the stringency of Governmental policies were evaluated. RESULTS: Uruguay, Paraguay, and Bolivia started earlier different prevention measures. The number of tests differs, as Chile is the 1 that makes more. Uruguay and Paraguay register fewer positive cases and deaths from COVID-19. The GHS index is led by Brazil, followed by Argentina, and then Chile. However, the INFORM index is led by Uruguay followed by Argentina, while Chile and Paraguay are on par. CONCLUSION: The countries that took preventive measures earlier and carried out a more tests are the ones that are obtaining the best results against COVID-19.

Latanoprost-loaded phytantriol cubosomes for the treatment of glaucoma.

Glaucoma is a degenerative optic neuropathy characterized by increased intraocular pressure that if untreated can result in blindness. Ophthalmological drug therapy is a challenge of great clinical importance due to the diversity of ocular biological barriers which commonly causes limited or no effectiveness for drugs delivered through the eye. In this work, we proposed the development of nanosized cubic liquid crystals (cubosomes) as a new drug carrier system for latanoprost, an anti-glaucoma drug. Latanoprost-loaded phytantriol cubosomes (CubLnp) were prepared using a top-down method. Latanoprost concentration in the formulations ranged from 0.00125% to 0.02% w/v. All cubosomes displayed an average size around 200 nm, a low polydispersity index of 0.1 and zeta potential values around -25 mV, with an encapsulation efficiency of about 90%. Structural studies revealed that cubosomes displayed a double-diamond surface, Pn3m cubic-phase structure, and was not affected by drug loading. Calorimetric studies revealed a fast and exothermic interaction between latanoprost and cubosomes. According to in vitro essays, latanoprost release from cubosomes was slow in time, evidencing a sustained release profile. Based on this behavior, the in vivo hypotensive intraocular effect was evaluated by means of the subconjunctival administration of CubLnp in normotensive rabbits. We obtained promising results in comparison with a marketed latanoprost formulation (0.005% w/v).

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.

Neuroprotective effect of melatonin loaded in ethylcellulose nanoparticles applied topically in a retinal degeneration model in rabbits.

We are reporting for the first time the synthesis and application of an innovative nanometric system for the controlled topic release of melatonin in the retina. The ethylcellulose nanocapsules were characterized by diverse physicochemical techniques (scanning electron microscopy, zeta potential, hydrodynamic diameters) and an in vitro release study was done. A complete ex vivo and in vivo trans-corneal permeation and an irritation study were carried out with the new formulations in albino rabbits, to which a retinal degenerative model was induced. The results obtained demonstrate that the in vitro release of melatonin (1 mg/mL and 2 mg/mL) transported by nanocapsules is slower when compared to a solution of melatonin. Greater penetration of melatonin through the cornea was demonstrated by ex vivo and in vivo tests. This can be attributable to an enhanced neuroprotective effect of melatonin on retinal ganglion cells when it is included in ethylcellulose nanocapsules compared to a solution of melatonin. These outstanding findings add promising new perspectives to current knowledge about administrations using nano-technological tools in the treatment of neurodegenerative diseases at the ocular level.

Ricobendazole nanocrystals obtained by media milling and spray drying: Pharmacokinetic comparison with the micronized form of the drug.

Helminthic infections are produced by different types of worms and affect millions of people worldwide. Benzimidazole compounds such as ricobendazole (RBZ) are widely used to treat helminthiasis. However, their low aqueous solubility leads to poor gastrointestinal dissolution, absorption and potential lack of efficacy. The formulation of nanocrystals (NCs) have become the strategy of preference for hydrophobic drugs. In this work, we prepared RBZ NCs (RBZ-NCs) by an optimized combination of bead milling and spray-drying. Following the physicochemical characterization, a comparative pharmacokinetic evaluation of RBZ-NCs was performed in dogs using as controls a micronized powdered form of RBZ (mRBZ) and a physical mixture of drug and stabilizer 1:1 (PM). The particle size of the redispersed RBZ-NCs was 181.30 ± 5.93 nm, whereas DSC, PXRD and FTIR analyses demonstrated that the active ingredient RBZ remained physicochemically unchanged after the manufacture process. RBZ-NCs exhibited improved in vitro biopharmaceutical behaviour when compared to mRBZ. Consequently, the pharmacokinetic trial demonstrated a significant increase in the drug oral absorption, with an AUC0-∞ 1.9-fold higher in comparison to that obtained in animals treated with mRBZ. This novel formulation holds substantial potential for the development of new/alternative treatments for helminth infections both in human and veterinary medicine.

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.

A Natural Peanut Edible Coating Enhances the Chemical and Sensory Stability of Roasted Peanuts.

This study aims to assess the enhancement of the chemical and sensory properties of roasted peanuts during storage, through the application of high-protein defatted peanut flour (DPF) coatings incorporated with and without antioxidants. The control sample without coating, packed in normal atmosphere (control), showed the highest conjugated dienes (CD) increment (from 1.17 on day 0 to 3.60 on day 180). Roasted peanuts without coating, packed in high barrier bags under vacuum, reached the lowest CD at day 180 (1.92). Conjugated trienes and peroxide values were analogous to CD. The control exhibited the greatest decrease in α-tocopherol (from 27.65 mg/100 g on day 0 to 21.32 mg/100 g on day 180) and γ-tocopherol (from 21.91 mg/100 g on day 0 to 14.99 mg/100 g on day 180). 3-Methylpyridine and 2,5-dimethylpyrazine decreased with storage time only for the control, which had the highest increase in oxidized flavor (from 0 on day 0 to 13.30 on day 180), cardboard (from 7.67 on day 0 to 15.23 on day 180), and astringency. The lowest decreases in roasted peanutty scores were seen in coated samples. DPF coatings delayed roasted peanuts oxidation, enhancing their sensory properties and shelf life compared with the control sample. PRACTICAL APPLICATION: Defatted peanut flour (DPF) is a byproduct obtained during peanut oil extraction and is a possible material for edible film preparation. This strategy adds value to the peanut industry by transforming a by-product into a material with the potential to develop biodegradable and economical films. The application of this DPF-based edible coating on the surface of roasted peanuts may have contributed to extent product's shelf life, allowing for coated products to be packaged in lower barrier and less expensive materials. Use of peanut material to coat peanuts avoids the risk of allergen protein cross contamination, which would be highly valuable for the food industry.

Albendazole-lipid nanocapsules: Optimization, characterization and chemoprophylactic efficacy in mice infected with Echinococcus granulosus.

Cystic echinococcosis (CE), which is caused during the metacestode larval stage of Echinococcus granulosus, is a life-threatening disease and is very difficult to treat. At present, the FDA-approved antihelmintic drugs are mebendazole (MBZ), albendazole (ABZ) and its principal metabolite ABZ sulfoxide (ABZSO), but as these have a therapeutic efficacy over 50%, underlining the need for new drug delivery systems. The aim of this work was the optimization and characterization of previously developed ABZ lipid nanocapsules (ABZ-LNCs) and evaluate their efficacy in mice infected with E. granulosus. LNCs were prepared by the phase inversion technique and characterized in terms of size, surface charge, drug loading, and in vitro stability followed by an in vivo proof-of-concept using a murine model infected with E. granulosus. Stable particle dispersions with a narrow size distribution and high efficiency of encapsulation (≥90%) were obtained. ABZ-LNCs showed a greater chemoprophylactic efficacy than ABZ suspension administered by the oral route as 4 out of the 10 ABZ-LNCs treated mice did not develop any cysts, whereas the infection progressed in all mice from the ABZ suspension group. Regarding the ultrastructural studies of cysts, mice treated with ABZ-LNCs or ABZ suspension revealed changes in the germinal layer. However, the extent of the damage appeared to be greater after ABZ-LNC administration compared to the suspension treatment. These results suggest that ABZ-LNCs could be a promising novel candidate for ABZ delivery to treat CE.

Protective role of melatonin on retinal ganglionar cell: In vitro an in vivo evidences.

Oxidative stress triggers ocular neurodegenerative diseases, such as glaucoma or macular degeneration. The increase of reactive oxygen and nitrogen species in retinal ganglion cells (RGCs) causes damage to the structure and function of the axons that make up the optic nerve, leading to cell death arising from apoptosis, necrosis or autophagy in the RCGs. The use of antioxidants to prevent visual neurodegenerative pathologies is a novel and possibly valuable therapeutic strategy. To investigate in vitro and in vivo neuroprotective efficacy of melatonin (MEL) in RGCs, we used a model of oxidative glutamate (GLUT) toxicity in combination with l-butionin-S, R-sulfoximine (BSO), which induces cell death by apoptosis through cytotoxicity and oxidative stress mechanisms. Histological sectioning and immunohistochemical assays using the TUNEL technique were performed to determine the damage generated in affected cells and to observe the death process of RGCs. Whit BSO-GLUT the results revealed a progressive RGCs death without any significant evidence of a decreased retinal function after 9 days of treatment. In this way, we were able to develop a retinal degeneration model in vivo to carry out treatment with MEL and observed an increase in the survival percentage of RGCs, showing that BSO-GLUT could not exert an oxidant effect on cells to counteract the effect of MEL. These findings reveal that MEL has a neuroprotective and antiapoptotic effect as evidenced by the reduction of oxidative stress damage. MEL demonstrated in this model makes it a promising neuroprotective agent for the treatment of ocular neurodegenerative diseases when administered locally.

Class-B CpG-ODN Formulated With a Nanostructure Induces Type I Interferons-Dependent and CD4+ T Cell-Independent CD8+ T-Cell Response Against Unconjugated Protein Antigen.

There is a need for new vaccine adjuvant strategies that offer both vigorous antibody and T-cell mediated protection to combat difficult intracellular pathogens and cancer. To this aim, we formulated class-B synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) with a nanostructure (Coa-ASC16 or coagel) formed by self-assembly of 6-0-ascorbyl palmitate ester. Our previous results demonstrated that mice immunized with ovalbumin (OVA) and CpG-ODN formulated with Coa-ASC16 (OVA/CpG-ODN/Coa-ASC16) elicited strong antibodies (IgG1 and IgG2a) and Th1/Th17 cellular responses without toxic systemic effects. These responses were superior to those induced by a solution of OVA with CpG-ODN or OVA/CpG-ODN formulated with aluminum salts. In this study, we investigated the capacity of this adjuvant strategy (CpG-ODN/Coa-ASC16) to elicit CD8+ T-cell response and some of the underlying cellular and molecular mechanisms involved in adaptive response. We also analyzed whether this adjuvant strategy allows a switch from an immunization scheme of three-doses to one of single-dose. Our results demonstrated that vaccination with OVA/CpG-ODN/Coa-ASC16 elicited an antigen-specific long-lasting humoral response and importantly-high quality CD8+ T-cell immunity with a single-dose immunization. Moreover, Coa-ASC16 promoted co-uptake of OVA and CpG-ODN by dendritic cells. The CD8+ T-cell response induced by OVA/CpG-ODN/Coa-ASC16 was dependent of type I interferons and independent of CD4+ T-cells, and showed polyfunctionality and efficiency against an intracellular pathogen. Furthermore, the cellular and humoral responses elicited by the nanostructured formulation were IL-6-independent. This system provides a simple and inexpensive adjuvant strategy with great potential for future rationally designed vaccines.

[Comparison of two experimental models of glaucoma in rabbits] / Comparación de dos modelos experimentales de glaucoma en conejos.

Objective: to compare two models of experimental glaucoma by induction of ocular hypertension in rabbits. Materials and methods: Sixteen New Zealand female rabbits, 2-3 kg were used. Model A (n=6): cauterization of episcleral and perilimbar veins of the right eye (RE) with surgical electrocautery. Model B (n=10): Injection of ?-chymotrypsin in posterior chamber of RE. Intraocular pressure (IOP) was measured before and after the induction of ocular hypertension (OHT), once a week at the same time of day for 40 days, with a manual tonometer. The animals were euthanized by CO2 inhalation. In both models the control was the IOP of the left eye (LE). The mean and standard error (SE) values of IOP, expressed in mmHg, were compared statistically by applying Student's t-test with a significance level of p<0.05. Results: The IOP in LE (control) of model A: was 12.9±1.05 and in model B: 12.9±1.09. There were no significant differences between the models. Model A: The IOP increase in RE was 14.7% (14.8±1.4) with respect to LE. A significant increase in IOP was observed within the first 24 hours: 23.5±1.9 (p<0.05) compared to the control eye. There were no significant differences with subsequent controls. Model B: The increase in IOP in RE was 129.1% (29.6±3.4) with respect to LE. In all cases an increase was observed from Day 1 (p<0.05). The IOP peak in RE was evidenced on Day 25: 35±3.4 (p<0.05). The increase in IOP induced by model B was significantly higher (p<0.01) than in model A. There was loss of ganglion cells of the retina in both models, but the following anatomo-pathological changes were observed only in model B: buphthalmos, subluxation of the lens and increased excavation of the papilla. Conclusion: This study indicates that model B is the most appropriate method to induce a rapid, controlled increase of IOP in rabbits and, more importantly, that this increase may be sustained over extended periods of time. This model could be useful for evaluating the efficacy of new ocular drug delivery systems and for further studies of the physiopathology of glaucoma.

Objetivo: comparar dos modelos de glaucoma experimental por inducción de hipertensión ocular en conejos y describir cambios anatomo-patológicos. Materiales y métodos: Se utilizaron 16 conejos New Zealand, hembras, de 2-3 kg. Modelo A (n=6): cauterización de venas epiesclerales y perilimbares en ojo derecho (OD) con cauterio eléctrico quirúrgico. Modelo B (n=10): inyección intracamerular en OD de ?-quimotripsina. Se midió la presión intraocular (PIO) antes y después de la inducción de la hipertensión ocular (HTO), una vez por semana, a la misma hora del día, durante 40 días, con tonómetro manual. Los animales fueron sacrificados por inhalación de CO2. En ambos modelos la PIO del ojo izquierdo (OI).fue tomado como valor control. La media y error estándar (EE) de los valores de la PIO, expresada en mmHg, fueron evaluadas y comparadas estadísticamente aplicando Test T de Student considerando un nivel de significación de p < 0.05. Resultados: La PIO en OI (control) del modelo A: fue 12,9±1,05 y en el modelo B: 12,9±1,09. No se observaron diferencias significativas entre ambas. Modelo A: el aumento de la PIO en OD fue 14,7% (14,8±1,4) con respecto a OI. Se observó un incremento significativo de la PIO dentro de las primeras 24 hs: 23,5±1,9 (p<0,05) comparado con el valor del ojo control. No hubo diferencias significativas con los controles posteriores. Modelo B: el aumento de la PIO en OD fue 129,1% (29,6±3,4) con respecto al OI. En todos los casos se observó un incremento desde el día 1 (p<0,05). El pico de PIO en OD se evidenció el día 25: 35±3,4 (p<0,05). El incremento de la PIO inducida en el modelo B fue significativamente mayor (p<0,01) que en el modelo A. En ambos modelos hubo pérdida de células ganglionares de la retina, pero sólo en el modelo B se observaron los siguientes cambios anatomo-patológicos: buftalmus, subluxación del cristalino y aumento de la excavación de la papila. Conclusión: De acuerdo a este estudio, el modelo B aparece como el método más apropiado a los fines de inducir un incremento rápido y controlado de la IOP en conejos y más importante, este incremento sería capaz de mantenerse alto a lo largo de periodos de tiempos extendidos. Este modelo podría ser de gran utilidad para evaluar la eficacia de nuevos sistemas oculares de liberación de fármacos y realizar futuros estudios de la fisiopatología del glaucoma Conclusión: De acuerdo a este estudio, el modelo B aparece como el método más apropiado a los fines de inducir un incremento rápido y controlado de la IOP en conejos y más importante, este incremento sería capaz de mantenerse alto a lo largo de periodos de tiempos extendidos. Este modelo podría ser de gran utilidad para evaluar la eficacia de nuevos sistemas oculares de liberación de fármacos y realizar futuros estudios de la fisiopatología del glaucoma

Albendazole nanocrystals with improved pharmacokinetic performance in mice.

AIM: Albendazole (ABZ) is a broad-spectrum antiparasitic agent with poor aqueous solubility, which leads to poor/erratic bioavailability and therapeutic failures. Here, we aimed to produce a novel formulation of ABZ nanocrystals (ABZNC) and assess its pharmacokinetic performance in mice. Results/methodology: ABZNC were prepared by high-pressure homogenization and spray-drying processes. Redispersion capacity and solid yield were measured in order to obtain an optimized product. The final particle size was 415.69±7.40 nm and the solid yield was 72.32%. The pharmacokinetic parameters obtained in a mice model for ABZNC were enhanced (p < 0.05) with respect to the control formulation. CONCLUSION: ABZNC with improved pharmacokinetic behavior were produced by a simple, inexpensive and potentially scalable methodology.

A nanocrystal-based formulation improves the pharmacokinetic performance and therapeutic response of albendazole in dogs.

OBJECTIVES: Here, we aimed to assess the pharmacokinetic performance and therapeutic response (anthelmintic efficacy) of an albendazole (ABZ) nano-sized formulation in dogs. METHODS: In the pharmacokinetic study, ABZ self-dispersible nanocrystals (SDNCS) and a control formulation were administered orally to healthy dogs (n = 6). The concentrations of the sulphoxide metabolite in plasma were determined by high-performance liquid chromatography. For the anthelmintic efficacy trial, SDNCS and a commercially available formulation of ABZ were given to naturally parasitised dogs. The number of Ancylostoma caninum eggs in the faeces was determined using the McMaster technique. KEY FINDINGS: The area under the curve, Tmax and Cmax for the SDNCS were improved compared to the control. The efficacy study showed no statistical differences between the SDNCS and the commercial formulation at the doses of 25 and 12.5 mg/kg. However, significant differences (P < 0.05) between the treatments were found at 6.25 mg/kg (a quarter of the reference dose) with a reduction in the faecal nematode egg counts of 62.0 ± 21.1% and 100 ± 0% for the control and SDNCS, respectively. CONCLUSIONS: The improved pharmacokinetic performance observed for the novel formulation of ABZ correlated with an improved in vivo therapeutic response against a model intestinal nematode parasite in dogs.

Antioxidant Stability Study of Oregano Essential Oil Microcapsules Prepared by Spray-Drying.

Release kinetics of the volatile compounds of oregano EO microcapsules and the relation with the antioxidant activity were studied. Different wall material (WM) to core (C) ratios (1:1 and 2:1; WM:C), addition of colloidal silicon dioxide (CSD); and different storage conditions: 23 °C (room temperature; R) and 4 °C (fridge temperature; F) were evaluated for 90 d. Volatile compounds, total phenolic content (TPC), free radical scavenging activity (FRSA), and Trolox equivalent antioxidant capacity (TEAC) were measured. The formulas 2:1 (WM:C) (R and F) without CSD behaved differently from the rest, exhibited a higher antioxidant activity, and released less amount of volatile compounds after 90 d. These treatments grouped together in the cluster analysis, showing the highest TPC (81.54 mg gallic ac/g), FRSA (8.66%), and TEAC (12.35 µg Trolox/g). The addition of CSD facilitated the released of volatile compounds through storage time and promoted losses in the antioxidant activity. The temperature had a significant effect in most of the evaluated variables. However, this effect was more noticeable in F2 (1:1, CSD). PRACTICAL APPLICATION: Oregano essential oil has antioxidant, antimicrobial, and sensory preserving properties. However, it is susceptible to volatilization and is degraded by external factors. Its addition into food matrices is restricted due to low solubility and hydrophobicity. The antioxidant activity of oregano EO is preserved after the process of microencapsulation by spray-drying that extends its stability during storage. Oregano EO microcapsules are an alternative of delivery which protects and extends the shelf life of this essential oil, overcomes stability related limitations and preserves its desirable characteristics allowing these kind of microcapsules to be later incorporated into food products. These microcapsules could be used as a natural additive/flavouring with antioxidant properties.