Person:
Torrado Durán, Juan José

First Name

Juan José

Last Name

Torrado Durán

URI

https://hdl.handle.net/20.500.14352/77731

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Farmacia Galénica y Tecnología Alimentaria

Area

Farmacia y Tecnología Farmaceútica

Identifiers

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Now showing 1 - 10 of 24

Leveraging 3D-printed microfluidic micromixers for the continuous manufacture of melatonin loaded SNEDDS with enhanced antioxidant activity and skin permeability
(International Journal of Pharmaceutics, 2024) Ongoren, Baris; Aytug, Kara; Casettari, Luca; Tiboni, Mattia; Lalatsa, Aikaterini; Sanz Pérez, Amadeo; González Burgos, Elena María; Romero Martínez, Manuel Alejandro; Juberías, Antonio; Torrado Durán, Juan José; Serrano López, Dolores Remedios
Vesicants are chemical warfare agents (CWAs) capable of causing severe skin damage and systemic toxicity. Melatonin, known for its anti-inflammatory and antioxidant properties, can mitigate the effects of these agents. Self-nano-emulsifying drug delivery systems (SNEDDS) containing a high melatonin concentration (5 %, 50 mg/g) were optimized using a quality-by-design approach from biocompatible, non-irritant excipients with a particle size of about 100 nm. The melatonin-loaded SNEDDS showed a 43-fold greater permeability than a conventional melatonin cream. Chemical stability at ambient temperature (25 °C) was maintained for one year. The preparation of optimised melatonin-loaded SNEDDS using a simple mixing method was compared to microfluidic micromixers. Mixing was successfully achieved using a 3D-printed (fused deposition modeling or stereolithography) T-shaped toroidal microfluidic chip (with a channel geometry optimized by computational fluid dynamics), resulting in a scalable, continuous process for the first time with a substantial reduction in preparation time compared to other conventional mixing approaches. No statistically significant differences were observed in the key quality attributes, such as particle size and melatonin loading, between mixing method till kinetic equilibrium solubility is reached and mixing using the 3D-printed micromixers. This scalable, continuous, cost-effective approach improves the overall efficiency of SNEDDS production, reduces the cost of quality control for multiple batches, and demonstrates the potential of continuous microfluidic manufacture with readily customizable 3D-printed micromixers at points of care, such as military bases.
Leveraging 3D-Printed Microfluidic Micromixers for the Continuous Manufacture of Melatonin Loaded SNEDDS with Enhanced Antioxidant Activity and Skin Permeability
(International Journal of Pharmaceutics, 2024) Ongoren, Baris; Kara, Aytug; Casettari, Luca; Tiboni, Mattia; Lalatsa, A.; Sanz-Perez, A.; González Burgos, Elena María; Romero Martínez, Manuel Alejandro; Juderías, Antonio; Torrado Durán, Juan José; Serrano López, Dolores Remedios
Vesicants are chemical warfare agents (CWAs) capable of causing severe skin damage and systemic toxicity. Melatonin, known for its anti-inflammatory and antioxidant properties, can mitigate the effects of these agents. Self-nano-emulsifying drug delivery systems (SNEDDS) containing a high melatonin concentration (5%, 50 mg/g) were optimized using a quality-by-design approach from biocompatible, non-irritant excipients with a particle size of about 100 nm. The melatonin-loaded SNEDDS showed a 43-fold greater permeability than a conventional melatonin cream. Chemical stability at ambient temperature (25oC) was maintained for one year. The preparation of optimised melatonin-loaded SNEDDS using a simple mixing method was compared to microfluidic micromixers. Mixing was successfully achieved using a 3D-printed (fused deposition modeling or stereolithography) T-shaped toroidal microfluidic chip (with a channel geometry optimized by computational fluid dynamics), resulting in a scalable, continuous process for the first time with a substantial reduction in preparation time compared to other conventional mixing approaches. No statistically significant differences were observed in the key quality attributes, such as particle size and melatonin loading, between mixing method till kinetic equilibrium solubility is reached and mixing using the 3D-printed micromixers. This scalable, continuous, cost-effective approach improves the overall efficiency of SNEDDS production, reduces the cost of quality control for multiple batches, and demonstrates the potential of continuous microfluidic manufacture with readily customizable 3D-printed micromixers at points of care, such as military bases.
In Vitro and In Vivo Characteristics of Olive Oil as Excipient for Topical Administration
(Pharmaceutics, 2022) Rodríguez-Torrado, Marta; Kara, Aytug ; Romero Martínez, Manuel Alejandro; Juberías, Antonio; Torrado Durán, Juan José; Serrano López, Dolores Remedios
Oily excipients are vital components of dermatological products. In this study, the in vitro and in vivo characteristics of Wild Olive Oil (WOO) were compared with two other types of olive oils: Extra Virgin Olive Oil (EVOO) and Virgin Olive Oil (VOO). This work has also included Liquid Paraffin (LP) and Rosehip Oil (RO) as reference oils. Melatonin was used in the study as a model drug to demonstrate the antioxidant capacity of the oils. The melatonin carrier capacity and antioxidant performance was related to the degree of unsaturation of the oils and was highest for RO and WOO and lowest for LP. However, the most stable oil to oxidation was LP. The in vivo performance of the oils in the skin of eight healthy volunteers was investigated with a dermoanalyser. The highest increment of oil and hydration in the skin was obtained with RO. The lowest perception of oiliness was described for WOO, which produced the highest increase in elasticity of the skin area where it was applied. An in vitro-in vivo correlation was therefore performed through multivariable analysis (MVA).
Project number: PIMCD340/23-24
Creación de nuevos recursos educativos virtuales para estudiantes de grado en Farmacia
(2024) Torrado Durán, Susana; Álvarez Álvarez, Covadonga; Ares Lombán, Irma; Ballesteros Papantonakis, María De La Paloma; Fernandez Gutierrez, Jesus Miguel; Franco Gil, Maria Elviva; Lopez Suero, Marta; Martínez Caballero, Marta; Martínez Caballero, María Aranzazu; Notivoli Diez, Pablo; Rodriguez Torrado, David; Rodriguez Torrado, Marta; Torrado Duran, Santiago; Torrado Durán, Juan José; Torrado Durán, Santiago; Torrado Salmerón, Carlos Félix; Torre Iglesias, Paloma Marina De La; Torres Pabon, Norma Sofía; Torrado Durán, Susana
El objetivo del proyecto es la mejora de la enseñanza virtual a los alumnos del Grado en Farmacia mediante la realización de diversos recursos educativos abiertos virtuales, como vídeos o cuestionarios, que faciliten el aprendizaje.
In vitro effect of new formulations of amphotericin B on amastigote and promastigote forms of Leishmania infantum
(International journal of antimicrobial agents, 2007) Ordóñez Gutiérrez, Lara; Espada Fernández, Raquel; Dea Ayuela, María Auxiliadora; Torrado Durán, Juan José; Bolas Fernández, Francisco; Alunda Rodríguez, José María
The in vitro antileishmanial activities of various new amphotericin B (AMB) formulations were investigated, including microspheres of hydrophilic albumin with three AMB aggregation forms (monomeric, dimeric and multiaggregate) and the polymers of polylactic-co-glycolic acid, Resomer RG502 and RG503 with the multiaggregate AMB form. This in vitro study was performed on the extracellular promastigote form and the intracellular amastigote form of a canine strain of Leishmania infantum (UCM 20) using the infected J774 murine macrophage-like cell line. Albumin-encapsulated forms did not show any toxicity for murine cells and had lower median effective concentration (EC50) values (ca. 0.003 microg/mL) for L. infantum amastigotes than free formulations (0.03 microg/mL). In addition, the aggregation state of AMB had a notable effect on the antileishmanial activity of the drug. Results obtained in vitro point towards interest in monomeric AMB encapsulated in microspheres in the chemotherapeutic control of leishmaniasis.
Project number: 291
Creación de nuevo recurso educativo virtual para estudiantes de grado en Farmacia.
(2023) Torrado Durán, Susana; Álvarez Álvarez, Covadonga; Ares Lombán, Irma; Ballesteros Papantonakis, María De La Paloma; Fernández Gutierrez, Jesús Miguel; Franco Gil, María Elvira; Martínez Caballero, María Aranzazu; Martínez Caballero, Marta; Notivoli Díez, Pablo; Rodríguez Torrado, David; Rodríguez Torrado, Marta; Torrado Salmerón, Carlos Félix; Torrado Durán, Guillermo; Torrado Durán, Juan José; Torrado Durán, Santiago; Torre Iglesias, Paloma Marina De La
Creación de nuevo recurso educativo virtual para estudiantes de grado en Farmacia. El presente proyecto es continuación de un proyecto concedido con financiación el año 2019 y en él se continuarán desarrollando nuevos recursos educativos virtuales como los que ya se han hecho este curso, y que han tenido excelente acogida por los alumnos, para facilitar la adquisición del conocimiento de los estudiantes de Farmacia especialmente de aquellos temas en los que la bibliografía disponible es escasa como en el caso de la Asignatura de Tecnología Farmacéutica III en los temas dedicados a la industria farmacéutica.
Antifungal and Antiparasitic Drug Delivery
(Pharmaceutics, 2020) Torrado Durán, Juan José; Serrano López, Dolores Remedios; Capilla, Javier
Fungal and parasitic diseases affect more than a billion people across the globe, one-sixth of the world’s population, mostly located in developing countries. The lack of effective and safer treatments combined with a deficient diagnosis lead to serious chronic illness or even death. There is a mismatch between the rate of drug resistance and the development of new medicines. Formulation of antifungal and antiparasitic drugs adapted to different administration routes is challenging, bearing in mind their poor water solubility, which limits their bioavailability and efficacy. Hence, there is an unmet clinical need to develop vaccines and novel formulations and drug delivery strategies that can improve the bioavailability and therapeutic effect by enhancing their dissolution, increasing their chemical potency, stabilising the drug and targeting high concentration of drug to the infection sites. This Editorial regards the ten research contributions presented in the Special Issue “Antifungal and Antiparasitic Drug Delivery”.
New amphotericin B-gamma cyclodextrin formulation for topical use with synergistic activity against diverse fungal species and Leishmania spp.
(International journal of pharmaceutics, 2014) Ruiz, Helga K.; Serrano López, Dolores Remedios; Dea Ayuela, María Auxiliadora; Bilbao Ramos, Pablo Estanislao; Bolas Fernández, Francisco; Torrado Durán, Juan José; Molero, Gloria
Amphotericin B (AmB) has a broad antifungal and leishmanicidal activity with low incidence of clinical resistance. Its parenteral administration has high risk of nephrotoxicity that limits its use. In order to treat cutaneous infections, AmB topical administration is a safer therapy because of the low systemic absorption of the drug across mucous membranes. Moreover, in some developing countries both fungal topical infections and cutaneous leishmaniasis are an important health problem. The aim of this work is to formulate a topical amphotericin preparation and test its in vitro antifungal (against 11 different fungal species) and antileishmanial activity. γ-Cyclodextrin (γ-CD) was chosen to solubilise AmB. Furthermore, γ-CD has shown a synergistic effect on membrane destabilization with AmB. Topical novel formulations based on AmB-CD complex have exhibited greater antifungal activity (48%, 28% and 60% higher) when compared to AmB Neo-Sensitabs(®) disks, AmB dissolved in dimethyl sulfoxide (DMSO) and Clotrimazole(®) cream, respectively. Furthermore, AmB-CD methyl cellulose gel has shown significantly higher inhibition activity on biofilm formation, larger penetration through yeast biofilms and higher fungicidal activity on biofilm cells compared to AmB dissolved in DMSO. In addition, AmB-CD gel exhibited both high in vitro leishmanicidal efficacy with wider therapeutic index (between 2 and 8-fold higher than AmB deoxycholate depending on Leishmania spp.) and also in vivo activity in an experimental model of cutaneous leishmaniasis. These results illustrate the feasibility of a topical AmB formulation easy to prepare, physicochemically stable over 6 months, safe and effective against diverse fungal and parasitic cutaneous infections.
Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis
(Molecules, 2020) Bilbao Ramos, Pablo Estanislao; Serrano López, Dolores Remedios; Ruiz Saldaña, Helga Karina; Torrado Durán, Juan José; Bolas Fernández, Francisco; Dea Ayuela, María Auxiliadora
Leishmaniasis affects around 12 million people worldwide and is estimated to cause the ninth-largest disease burden. There are three main forms of the disease, visceral (VL), cutaneous (CL), and mucocutaneous (MCL), leading to more than one million new cases every year and several thousand deaths. Current treatments based on chemically synthesized molecules are far from ideal. In this study, we have tested the in vitro and in vivo efficacy of ursolic acid (UA), a multifunctional triterpenoid with well-known antitumoral, antioxidant, and antimicrobial effects on different Leishmania strains. The in vitro antileishmanial activity against the intracellular forms was six and three-fold higher compared to extracellular forms of L. amazonensis and L. infantum, respectively. UA also showed to be a potent antileishmanial drug against both VL and CL manifestations of the disease in experimental models. UA parenterally administered at 5 mg/kg for seven days significantly reduced the parasite burden in liver and spleen not only in murine acute infection but also in a chronic-infection model against L. infantum. In addition, UA ointment (0.2%) topically administered for four weeks diminished (50%) lesion size progression in a chronic infection model of CL caused by L. amazonensis, which was much greater than the effect of UA formulated as an O/W emulsion. UA played a key role in the immunological response modulating the Th1 response. The exposure of Leishmania-infected macrophages to UA led to a significant different production in the cytokine levels depending on the Leishmania strain causing the infection. In conclusion, UA can be a promising therapy against both CL and VL.
Project number: 254
Creación de nuevo recurso educativo virtual para estudiantes de grado en Farmacia
(2020) Torrado Durán, Susana; Ballesteros Papantonakis, María De La Paloma; Torrado Durán, Juan José; Torre Iglesias, Paloma Marina De La; Torrado Durán, Santiago; Álvarez Álvarez, Covadonga; Martínez Caballero, María Aranzazu; Martínez Caballero, Marta; Torrado Durán, Guillermo; Serrano López, Dolores Remedios; Ares Lombán, Irma; Torrado Salmerón, Carlos Félix; Rodríguez Torrado, Marta; Fernández Gutiérrez, Jesús Miguel; Rodríguez Torrado, David; Notivoli Díez, Pablo; Franco Gil, María Elvira