Daniela Quinteros - Academia.edu (original) (raw)
Papers by Daniela Quinteros
Journal of Vaccines and Immunology
This Mini-Review and Opinion letter, it was addressed different themes and topics implicated in t... more This Mini-Review and Opinion letter, it was addressed different themes and topics implicated in the development of new treatments and vaccines applied to pathologies developed in humans such as by Virus and related pathogens. In this context, it was presented and discussed different strategies used, which were contemplated from the design of small molecules, towards higher sized chemical structures and new Nanoarchitectures. In particular, it was discussed varied studies developed for the Corona Virus treatment; which afforded to the main mechanisms of action of pharmacophores and targeted functional Nanoparticles. In this direction, it was highlighted the importance of Bioconjugation of molecules and variable Nanoarchitectures for their incorporation within cells as well as for the development of Nano-vaccines. Moreover, it was discussed about the development of combinatory treatments based on different strategies recently reported. Similarly, it was presented different studies and...
European Journal of Pharmaceutical Sciences, 2017
The purpose of this study was to compare the in vivo efficacy of several timolol (TM)-loaded lipo... more The purpose of this study was to compare the in vivo efficacy of several timolol (TM)-loaded liposomal formulations with current TM antiglaucoma treatment (aqueous 0.5% w/v eye drops). In this study, conventional liposomes (CL) and deformable liposomes, without (DL1) and with ethanol (DL2) were prepared and characterized. In addition, in vitro release and permeation studies, as well as in vivo lowering intraocular pressure (IOP) and biocompatibility studies were performed. It was found that the quali and quantitative lipid bilayer composition played a significant role in modifying the physical properties of vesicles. The deformability study and electronic microscopy images revealed that membrane elasticity of DL1 and DL2 was much higher than CL. However, in vitro permeation results showed that the flux and permeability coefficient were significantly higher in CL compared to DL. The IOP study revealed that TM-loaded CL showed the best pharmacological activity, in comparison to deformable vesicles. Compared to the eye drops, CL formulation could equally reduce the IOP but using a concentration 10-fold lower, whereas the effective time was significantly longer. In addition, the formulations showed no irritant effects after instillation on the ocular surface.
Tópicos sobre Tecnología Farmacéutica, 2019
Este manual aborda los temas prioritarios en el campo de la tecnología farmacéutica y los avances... more Este manual aborda los temas prioritarios en el campo de la tecnología farmacéutica y los avances fundamentales que hubo en los últimos años a raíz de los estudios realizados en cada una de las formas farmacéuticas en todas las etapas de la producción de medicamentos. La progresiva introducción de los atributos de eficacia, seguridad y confiabilidad en su diseño y producción ?que se suman a los ya clásicos de identidad, pureza, potencia y estabilidad ha enriquecido la tecnología farmacéutica con la incorporación de metodologías y conocimientos que permiten satisfacer los nuevos requerimientos. Por ello, esta publicación pone especial énfasis en dar una visión tanto de la situación actual como de la perspectiva hacia el futuro cercano en cada tema, de manera que el lector pueda adquirir un panorama de la evolución de cada uno de los tópicos.Fil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Quinteros, Daniela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentin
Veterinary Immunology and Immunopathology, 2019
Subcellular vaccines against ovine contagious epididymitis due Brucella ovis can solve some short... more Subcellular vaccines against ovine contagious epididymitis due Brucella ovis can solve some shortcomings associated with the use of Brucella melitensis Rev 1. We have demonstrated that the parenteral immunization with polymeric antigen BLSOmp31 emulsified in oil adjuvant conferred significant protection against B. ovis in rams. In our previous studies, we have characterized chitosan microspheres (ChMs) and a thermoresponsive and mucoadhesive in situ gel (Poloxamer 407-Ch) as two novel formulation strategies for the delivery of BLSOmp31 in nasal as well as conjunctival mucosa. In the present work, we evaluated the immunogenicity and protection conferred by the intranasal and conjunctival immunization with these two mucosal delivery systems against B. ovis in rams. BLSOmp31-ChM administered by intranasal route and BLSOmp31-P407-Ch applied by intranasal or conjunctival routes induced systemic, local and preputial IgG and IgA antibody response. Neither formulation showed interference in the serological diagnosis. Thus, mucosal immunization using either formulation induced significant specific cellular immune responses (in vitro and in vivo) and it prevented the excretion of B. ovis in semen. Although these vaccines did not prevent infection in immunized rams, colonization reduction of infected organs and bacterial distribution differed significantly between vaccinated and unvaccinated rams.
Scientia Pharmaceutica, 2012
Equilibria and release properties of aqueous systems consisting of a set of five non-steroidal an... more Equilibria and release properties of aqueous systems consisting of a set of five non-steroidal anti-inflammatory drugs (AH) complexed with the cationic polymethacrylate Eudragit E 100 (EU) are reported in this study. The composition (EU(AH) 50 (HCl) 50) having fifty mole percent of each counterion (A − and Cl −) produces clear, stable aqueous dispersions in which a remarkably high proportion of AH (higher than 98%) is condensed with the PE under the form of ion pairs. This property expands the interval of pH in which AH are aqueous soluble. The set of AH contains members with and without an alpha methyl group (-(CH 3)CH-COOH: Flurbiprofen, Naproxen, Ketoprofen) and (-CH 2-COOH: Diclofenac, Indomethacin). The proportion of ion pairs in the complexes was lower in the former group. Release of AH from the complexes toward a saline (NaCl 0.9%) solution was assayed in Franz cells. The five complexes behaved as drug carriers that exhibited a slow drug release with a remarkable zero order. In line with the percentages of counterionic condensation observed, release rates from-(CH 3)CH-COOH complexes were clearly higher than those of-CH 2-COOH ones.
Journal of Veterinary Pharmacology and Therapeutics, 2013
An important frontier in the administration of therapeutic drugs to veterinary species is the use... more An important frontier in the administration of therapeutic drugs to veterinary species is the use of different polymers as drug delivery platforms. The usefulness of polymers as platforms for the administration of pharmaceutical and agricultural agents has been clearly recognized in the recent decades. The chemical versatility of polymers and the wide range of developed controlled-release strategies enhance the possibilities for the formulation of active molecules. In particular, the veterinary area offers opportunities for the development of novel controlled-release drug delivery technologies adapted to livestock or companion animal health needs. In some cases, it also allows to improve profitability in meat production or to meet the safety criteria related to drug residues. A number of factors affect the selection of polymers and subsequent properties of the controlled-release drug delivery system. However, their selection also dictates the release kinetics of the drug from the delivery system. Such choices are therefore crucial as they affect the success and potential of the delivery system for achieving the therapeutic goals of the veterinarian. It is the intention of this review to give an overview of the most relevant polymers, which are used or have been tested as drug delivery release rate modifiers in the veterinary field. The article highlights some recent developments focusing on their advantages and applications and analyzes the future direction of the scientific and technological advancements in this area.
Materials Science and Engineering: C, 2016
Transversality between mathematical modeling, pharmacology, and materials science is essential in... more Transversality between mathematical modeling, pharmacology, and materials science is essential in order to achieve controlled-release systems with advanced properties. In this regard, the area of biomaterials provides a platform for the development of depots that are able to achieve controlled release of a drug, whereas pharmacology strives to find new therapeutic molecules and mathematical models have a connecting function, providing a rational understanding by modeling the parameters that influence the release observed. Herein we present a mechanism which, based on reasonable assumptions, explains the experimental data obtained very well. In addition, we have developed a simple and accurate "lumped" kinetics model to correctly fit the experimentally observed drugrelease behavior. This lumped model allows us to have simple analytic solutions for the mass and rate of drug release as a function of time without limitations of time or mass of drug released, which represents an important step-forward in the area of in vitro drug delivery when compared to the current state of the art in mathematical modeling. As an example, we applied the mechanism and model to the release data for acetazolamide from a recombinant polymer. Both materials were selected because of a need to develop a suitable ophthalmic formulation for the treatment of glaucoma. The in vitro release model proposed herein provides a valuable predictive tool for ensuring product performance and batch-to-batch reproducibility, thus paving the way for the development of further pharmaceutical devices.
International Journal of Pharmaceutics
<p>Data are expressed as means ± SD (n = 3).</p><p>*Significant differences wit... more <p>Data are expressed as means ± SD (n = 3).</p><p>*Significant differences with formulation F2 (p-value<0.05).</p><p>pH, osmolarity, and viscosity data of the 5-MCA-NAT formulations.</p
<p>IOP, intraocular pressure; Maximum IOP reduction (%), percentage of reduction ± SEM; AUC... more <p>IOP, intraocular pressure; Maximum IOP reduction (%), percentage of reduction ± SEM; AUC<sub>0</sub><sup>8 h</sup>, ΔIOP (%) versus time (h) from 0 to 8 hours. Data are expressed as means ± SEM (n = 20 eyes).</p><p>*Significant differences with formulation F2 (p-value<0.05).</p><p>Maximum percent IOP reduction over 8 hours.</p
<p>Control Group: animals were administered 25 µL of saline solution in both eyes; F3 Group... more <p>Control Group: animals were administered 25 µL of saline solution in both eyes; F3 Group animals were instilled 25 µL of 5-MCA-NAT-loaded liposomes dispersed in 0.2% SH (F3) in both eyes; F4 Group: animals received 25 µL of 5-MCA-NAT-loaded liposomes dispersed in 0.5% CMC (F4). Data are expressed as means ± SD (n = 6).</p><p>*Significant differences with Control Group (p-value<0.05).</p><p>**Significant differences with Control Group (p-value<0.01).</p><p>Tear osmolarity in the 3 Study Groups.</p
This is an Open Access article distributed under the terms of the Creative Commons Attribution Li... more This is an Open Access article distributed under the terms of the Creative Commons Attribution License
Pharmacy & Pharmacology International Journal, 2021
Objective: Develop sterile vancomycin-amikacin reinforced antibiotics in smaller batches of finis... more Objective: Develop sterile vancomycin-amikacin reinforced antibiotics in smaller batches of finished products than those produced at the industrial level and under different working conditions. In this work, critical aspects concerning the elaboration process such as equipment and process evaluation, protocol development, physicochemical characterization, and microbiological tests were analyzed. In the first stage, the preparation of the formulations was carried out in the Department of Pharmaceutical Sciences of the Faculty of Chemical Sciences of the National University of Cordoba. In the second stage, the eye drops were prepared in the laboratory of Farmacia Vilarrubi, an office pharmacy authorized by the health authority and dedicated to the preparation of non-sterile compounding formulations. Both samples prepared at different manufacturing sites were subjected to the same physicochemical and microbiological tests. Methods and results: The sample compounding formulations of Vancomycin, Amikacin or their combination, at a dose of 30 mg/mL, were developed and subjected to physicochemical essays such as macroscopic observation, measurement of pH, osmolality, particle size, and quantification of drug concentration, during 7 days stored under adequate conditions of light and temperature. In addition, microbiological assays were carried out to verify their sterility and procedure under aseptic conditions. All the formulations made of reinforced antibiotic eye drops demonstrated high physicochemical and microbiological stability during the evaluated period. Conclusion: The reinforced antibiotic eye drops and the container used for their conservation showed correct sterility and microbiological stability during the time of use for the patient. It is possible to transfer small batch production of this type of quality sterile formulations to a pharmacy. For this, the training and education of the pharmaceutical professional is imperative.
Pharmaceutics, 2021
The purpose of this study was to design, for the first time, a co-loaded liposomal formulation (C... more The purpose of this study was to design, for the first time, a co-loaded liposomal formulation (CLL) for treatment of glaucoma including timolol maleate (TM) in the lipid bilayer and acetazolamide (Acz)-(2-hydroxy)propyl β-cyclodextrin (HPβCD) complexes (AczHP) solubilized in the aqueous core of liposomes. Formulations with TM (TM-L) and AczHP (AczHP-L), separately, were also prepared and characterized. A preliminary study comprising the Acz/HPβCD complexes and their interaction with cholesterol (a component of the lipid bilayer) was realized. Then, a screening study on formulation factors affecting the quality of the product was carried out following the design of the experiment methodology. In addition, in vitro release and permeation studies and in vivo lowering intraocular pressure (IOP) studies were performed. The results of the inclusion complexation behavior, characterization, and binding ability of Acz with HPβCD showed that HPβCD could enhance the water solubility of Acz de...
Investigative Ophthalmology & Visual Science, 2012
Disaster Medicine and Public Health Preparedness, 2021
Objective:In this work, in order to establish a better comprehension of the association between A... more 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 COV...
European Journal of Pharmaceutical Sciences, 2021
Glaucoma is a degenerative optic neuropathy characterized by increased intraocular pressure that ... more 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).
Experimental Eye Research, 2020
We are reporting for the first time the synthesis and application of an innovative nanometric sys... more 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.
Life Sciences, 2018
Oxidative stress triggers ocular neurodegenerative diseases, such as glaucoma or macular degenera... more 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, Rsulfoximine (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. 1. Introduction Various ocular pathologies such as glaucoma [1], age-related macular degeneration [2] and genetic retinal dystrophies [3,4] as well as many forms of retinal ischemia, are triggered by oxidative stress. Generally, these, diseases that affect the back of the eye, are chronic and degenerative with some of these being related to advanced age. The term "oxidative stress" refers to the situation in which the production of oxygen reactive species (ROS) attains pathological levels, and at this point the antioxidant capacity of the cell is insufficient to
Journal of Vaccines and Immunology
This Mini-Review and Opinion letter, it was addressed different themes and topics implicated in t... more This Mini-Review and Opinion letter, it was addressed different themes and topics implicated in the development of new treatments and vaccines applied to pathologies developed in humans such as by Virus and related pathogens. In this context, it was presented and discussed different strategies used, which were contemplated from the design of small molecules, towards higher sized chemical structures and new Nanoarchitectures. In particular, it was discussed varied studies developed for the Corona Virus treatment; which afforded to the main mechanisms of action of pharmacophores and targeted functional Nanoparticles. In this direction, it was highlighted the importance of Bioconjugation of molecules and variable Nanoarchitectures for their incorporation within cells as well as for the development of Nano-vaccines. Moreover, it was discussed about the development of combinatory treatments based on different strategies recently reported. Similarly, it was presented different studies and...
European Journal of Pharmaceutical Sciences, 2017
The purpose of this study was to compare the in vivo efficacy of several timolol (TM)-loaded lipo... more The purpose of this study was to compare the in vivo efficacy of several timolol (TM)-loaded liposomal formulations with current TM antiglaucoma treatment (aqueous 0.5% w/v eye drops). In this study, conventional liposomes (CL) and deformable liposomes, without (DL1) and with ethanol (DL2) were prepared and characterized. In addition, in vitro release and permeation studies, as well as in vivo lowering intraocular pressure (IOP) and biocompatibility studies were performed. It was found that the quali and quantitative lipid bilayer composition played a significant role in modifying the physical properties of vesicles. The deformability study and electronic microscopy images revealed that membrane elasticity of DL1 and DL2 was much higher than CL. However, in vitro permeation results showed that the flux and permeability coefficient were significantly higher in CL compared to DL. The IOP study revealed that TM-loaded CL showed the best pharmacological activity, in comparison to deformable vesicles. Compared to the eye drops, CL formulation could equally reduce the IOP but using a concentration 10-fold lower, whereas the effective time was significantly longer. In addition, the formulations showed no irritant effects after instillation on the ocular surface.
Tópicos sobre Tecnología Farmacéutica, 2019
Este manual aborda los temas prioritarios en el campo de la tecnología farmacéutica y los avances... more Este manual aborda los temas prioritarios en el campo de la tecnología farmacéutica y los avances fundamentales que hubo en los últimos años a raíz de los estudios realizados en cada una de las formas farmacéuticas en todas las etapas de la producción de medicamentos. La progresiva introducción de los atributos de eficacia, seguridad y confiabilidad en su diseño y producción ?que se suman a los ya clásicos de identidad, pureza, potencia y estabilidad ha enriquecido la tecnología farmacéutica con la incorporación de metodologías y conocimientos que permiten satisfacer los nuevos requerimientos. Por ello, esta publicación pone especial énfasis en dar una visión tanto de la situación actual como de la perspectiva hacia el futuro cercano en cada tema, de manera que el lector pueda adquirir un panorama de la evolución de cada uno de los tópicos.Fil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Quinteros, Daniela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentin
Veterinary Immunology and Immunopathology, 2019
Subcellular vaccines against ovine contagious epididymitis due Brucella ovis can solve some short... more Subcellular vaccines against ovine contagious epididymitis due Brucella ovis can solve some shortcomings associated with the use of Brucella melitensis Rev 1. We have demonstrated that the parenteral immunization with polymeric antigen BLSOmp31 emulsified in oil adjuvant conferred significant protection against B. ovis in rams. In our previous studies, we have characterized chitosan microspheres (ChMs) and a thermoresponsive and mucoadhesive in situ gel (Poloxamer 407-Ch) as two novel formulation strategies for the delivery of BLSOmp31 in nasal as well as conjunctival mucosa. In the present work, we evaluated the immunogenicity and protection conferred by the intranasal and conjunctival immunization with these two mucosal delivery systems against B. ovis in rams. BLSOmp31-ChM administered by intranasal route and BLSOmp31-P407-Ch applied by intranasal or conjunctival routes induced systemic, local and preputial IgG and IgA antibody response. Neither formulation showed interference in the serological diagnosis. Thus, mucosal immunization using either formulation induced significant specific cellular immune responses (in vitro and in vivo) and it prevented the excretion of B. ovis in semen. Although these vaccines did not prevent infection in immunized rams, colonization reduction of infected organs and bacterial distribution differed significantly between vaccinated and unvaccinated rams.
Scientia Pharmaceutica, 2012
Equilibria and release properties of aqueous systems consisting of a set of five non-steroidal an... more Equilibria and release properties of aqueous systems consisting of a set of five non-steroidal anti-inflammatory drugs (AH) complexed with the cationic polymethacrylate Eudragit E 100 (EU) are reported in this study. The composition (EU(AH) 50 (HCl) 50) having fifty mole percent of each counterion (A − and Cl −) produces clear, stable aqueous dispersions in which a remarkably high proportion of AH (higher than 98%) is condensed with the PE under the form of ion pairs. This property expands the interval of pH in which AH are aqueous soluble. The set of AH contains members with and without an alpha methyl group (-(CH 3)CH-COOH: Flurbiprofen, Naproxen, Ketoprofen) and (-CH 2-COOH: Diclofenac, Indomethacin). The proportion of ion pairs in the complexes was lower in the former group. Release of AH from the complexes toward a saline (NaCl 0.9%) solution was assayed in Franz cells. The five complexes behaved as drug carriers that exhibited a slow drug release with a remarkable zero order. In line with the percentages of counterionic condensation observed, release rates from-(CH 3)CH-COOH complexes were clearly higher than those of-CH 2-COOH ones.
Journal of Veterinary Pharmacology and Therapeutics, 2013
An important frontier in the administration of therapeutic drugs to veterinary species is the use... more An important frontier in the administration of therapeutic drugs to veterinary species is the use of different polymers as drug delivery platforms. The usefulness of polymers as platforms for the administration of pharmaceutical and agricultural agents has been clearly recognized in the recent decades. The chemical versatility of polymers and the wide range of developed controlled-release strategies enhance the possibilities for the formulation of active molecules. In particular, the veterinary area offers opportunities for the development of novel controlled-release drug delivery technologies adapted to livestock or companion animal health needs. In some cases, it also allows to improve profitability in meat production or to meet the safety criteria related to drug residues. A number of factors affect the selection of polymers and subsequent properties of the controlled-release drug delivery system. However, their selection also dictates the release kinetics of the drug from the delivery system. Such choices are therefore crucial as they affect the success and potential of the delivery system for achieving the therapeutic goals of the veterinarian. It is the intention of this review to give an overview of the most relevant polymers, which are used or have been tested as drug delivery release rate modifiers in the veterinary field. The article highlights some recent developments focusing on their advantages and applications and analyzes the future direction of the scientific and technological advancements in this area.
Materials Science and Engineering: C, 2016
Transversality between mathematical modeling, pharmacology, and materials science is essential in... more Transversality between mathematical modeling, pharmacology, and materials science is essential in order to achieve controlled-release systems with advanced properties. In this regard, the area of biomaterials provides a platform for the development of depots that are able to achieve controlled release of a drug, whereas pharmacology strives to find new therapeutic molecules and mathematical models have a connecting function, providing a rational understanding by modeling the parameters that influence the release observed. Herein we present a mechanism which, based on reasonable assumptions, explains the experimental data obtained very well. In addition, we have developed a simple and accurate "lumped" kinetics model to correctly fit the experimentally observed drugrelease behavior. This lumped model allows us to have simple analytic solutions for the mass and rate of drug release as a function of time without limitations of time or mass of drug released, which represents an important step-forward in the area of in vitro drug delivery when compared to the current state of the art in mathematical modeling. As an example, we applied the mechanism and model to the release data for acetazolamide from a recombinant polymer. Both materials were selected because of a need to develop a suitable ophthalmic formulation for the treatment of glaucoma. The in vitro release model proposed herein provides a valuable predictive tool for ensuring product performance and batch-to-batch reproducibility, thus paving the way for the development of further pharmaceutical devices.
International Journal of Pharmaceutics
<p>Data are expressed as means ± SD (n = 3).</p><p>*Significant differences wit... more <p>Data are expressed as means ± SD (n = 3).</p><p>*Significant differences with formulation F2 (p-value<0.05).</p><p>pH, osmolarity, and viscosity data of the 5-MCA-NAT formulations.</p
<p>IOP, intraocular pressure; Maximum IOP reduction (%), percentage of reduction ± SEM; AUC... more <p>IOP, intraocular pressure; Maximum IOP reduction (%), percentage of reduction ± SEM; AUC<sub>0</sub><sup>8 h</sup>, ΔIOP (%) versus time (h) from 0 to 8 hours. Data are expressed as means ± SEM (n = 20 eyes).</p><p>*Significant differences with formulation F2 (p-value<0.05).</p><p>Maximum percent IOP reduction over 8 hours.</p
<p>Control Group: animals were administered 25 µL of saline solution in both eyes; F3 Group... more <p>Control Group: animals were administered 25 µL of saline solution in both eyes; F3 Group animals were instilled 25 µL of 5-MCA-NAT-loaded liposomes dispersed in 0.2% SH (F3) in both eyes; F4 Group: animals received 25 µL of 5-MCA-NAT-loaded liposomes dispersed in 0.5% CMC (F4). Data are expressed as means ± SD (n = 6).</p><p>*Significant differences with Control Group (p-value<0.05).</p><p>**Significant differences with Control Group (p-value<0.01).</p><p>Tear osmolarity in the 3 Study Groups.</p
This is an Open Access article distributed under the terms of the Creative Commons Attribution Li... more This is an Open Access article distributed under the terms of the Creative Commons Attribution License
Pharmacy & Pharmacology International Journal, 2021
Objective: Develop sterile vancomycin-amikacin reinforced antibiotics in smaller batches of finis... more Objective: Develop sterile vancomycin-amikacin reinforced antibiotics in smaller batches of finished products than those produced at the industrial level and under different working conditions. In this work, critical aspects concerning the elaboration process such as equipment and process evaluation, protocol development, physicochemical characterization, and microbiological tests were analyzed. In the first stage, the preparation of the formulations was carried out in the Department of Pharmaceutical Sciences of the Faculty of Chemical Sciences of the National University of Cordoba. In the second stage, the eye drops were prepared in the laboratory of Farmacia Vilarrubi, an office pharmacy authorized by the health authority and dedicated to the preparation of non-sterile compounding formulations. Both samples prepared at different manufacturing sites were subjected to the same physicochemical and microbiological tests. Methods and results: The sample compounding formulations of Vancomycin, Amikacin or their combination, at a dose of 30 mg/mL, were developed and subjected to physicochemical essays such as macroscopic observation, measurement of pH, osmolality, particle size, and quantification of drug concentration, during 7 days stored under adequate conditions of light and temperature. In addition, microbiological assays were carried out to verify their sterility and procedure under aseptic conditions. All the formulations made of reinforced antibiotic eye drops demonstrated high physicochemical and microbiological stability during the evaluated period. Conclusion: The reinforced antibiotic eye drops and the container used for their conservation showed correct sterility and microbiological stability during the time of use for the patient. It is possible to transfer small batch production of this type of quality sterile formulations to a pharmacy. For this, the training and education of the pharmaceutical professional is imperative.
Pharmaceutics, 2021
The purpose of this study was to design, for the first time, a co-loaded liposomal formulation (C... more The purpose of this study was to design, for the first time, a co-loaded liposomal formulation (CLL) for treatment of glaucoma including timolol maleate (TM) in the lipid bilayer and acetazolamide (Acz)-(2-hydroxy)propyl β-cyclodextrin (HPβCD) complexes (AczHP) solubilized in the aqueous core of liposomes. Formulations with TM (TM-L) and AczHP (AczHP-L), separately, were also prepared and characterized. A preliminary study comprising the Acz/HPβCD complexes and their interaction with cholesterol (a component of the lipid bilayer) was realized. Then, a screening study on formulation factors affecting the quality of the product was carried out following the design of the experiment methodology. In addition, in vitro release and permeation studies and in vivo lowering intraocular pressure (IOP) studies were performed. The results of the inclusion complexation behavior, characterization, and binding ability of Acz with HPβCD showed that HPβCD could enhance the water solubility of Acz de...
Investigative Ophthalmology & Visual Science, 2012
Disaster Medicine and Public Health Preparedness, 2021
Objective:In this work, in order to establish a better comprehension of the association between A... more 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 COV...
European Journal of Pharmaceutical Sciences, 2021
Glaucoma is a degenerative optic neuropathy characterized by increased intraocular pressure that ... more 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).
Experimental Eye Research, 2020
We are reporting for the first time the synthesis and application of an innovative nanometric sys... more 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.
Life Sciences, 2018
Oxidative stress triggers ocular neurodegenerative diseases, such as glaucoma or macular degenera... more 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, Rsulfoximine (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. 1. Introduction Various ocular pathologies such as glaucoma [1], age-related macular degeneration [2] and genetic retinal dystrophies [3,4] as well as many forms of retinal ischemia, are triggered by oxidative stress. Generally, these, diseases that affect the back of the eye, are chronic and degenerative with some of these being related to advanced age. The term "oxidative stress" refers to the situation in which the production of oxygen reactive species (ROS) attains pathological levels, and at this point the antioxidant capacity of the cell is insufficient to