Person:
Aparicio Blanco, Juan

First Name

Juan

Last Name

Aparicio Blanco

URI

https://hdl.handle.net/20.500.14352/77771

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Farmacia Galénica y Tecnología Alimentaria

Area

Farmacia y Tecnología Farmaceútica

Identifiers

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Search Results

Now showing 1 - 10 of 19

Size-Tailored Design of Highly Monodisperse Lipid Nanocapsules for Drug Delivery
(Journal of Biomedical Nanotechnology, 2019) Aparicio Blanco, Juan; Sebastián, Víctor ; Rodríguez-Amaro, Miguel ; García-Díaz, Héctor C. ; Torres Suárez, Ana Isabel
The empirical development of nanocarriers has unfortunately led to high attrition rates in clinical trials. This underpins the importance of the rational design of nanomedicines to achieve efficient disease-driven therapies. Since particle size certainly influences in vivo behaviour, rational disease-driven colloid design can only be achieved by determining the parameters that accurately control their size distribution. To this end, we have thoroughly revisited the parameters that drive the phase-inversion temperature nanoemulsification method to obtain kinetically stable and monodisperse lipid nanocapsules. Notably, we have evidenced that the major parameter driving nanocapsule formation is the oily phase/surfactant ratio and consequently, we have established a linear univariate mathematical model that predicts the particle size distribution for various oily phase-surfactant combinations (R 2 > 0 99). Furthermore, we have observed that the difference between the HLB values of the surfactants and the triglycerides utilized as oily phase correlates with the steepness of the slope of the linear mathematical model. This model will bring the implementation of size-tailored lipid drug carriers determined by pathophysiological features a step closer. Importantly, this model pioneeringly fits all data available in the literature on size distribution of colloids prepared by low-energy methods and that were originally evaluated following other parameters. Moreover, the nanocapsules have been obtained following a single-step process, with the ensuing potential for a future scale-up in an energetically-efficient manner. These findings will eventually enable nanomedicines to be obtained "on-demand" to meet disease-driven criteria in terms of particle size and will also increase their chances of success.
Glioblastoma chemotherapeutic agents used in the clinical setting and in clinical trials: Nanomedicine approaches to improve their efficacy
(International Journal of Pharmaceutics, 2020) Aparicio Blanco, Juan; Sanz-Arriazu, Lorena ; Lorenzoni, Ricardo ; Blanco-Prieto, María J.
Even though substantial advances in understanding glioma pathogenesis have prompted a more rational design of potential therapeutic strategies, glioblastoma multiforme remains an incurable disease with the lowest median overall survival among all malignant brain tumours. Therefore, there is a dire need to find novel drug delivery strategies to improve the current dismal survival outcomes. In this context, nanomedicine offers an appealing alternative as it shows potential to improve brain drug delivery. Accordingly, we here review nanomedicine-based drug delivery strategies tested in orthotopic animal models of glioblastoma intended to improve the efficacy of the drug candidates that are currently used in the clinical setting or that have entered clinical trials for the treatment of glioblastoma multiforme. We also outline the future perspectives of nanotechnology to provide emerging glioblastoma treatment with broad translational clinical potential based on the nanocarriers that have already entered the clinical trials stage for the treatment of malignant glioma.
Critical attributes of formulation and of elaboration process of PLGA-protein microparticles
(International Journal of Pharmaceutics, 2015) Martín Sabroso, Cristina; Fraguas Sánchez, Ana Isabel; Aparicio Blanco, Juan; Cano-Abad, M.F.; Torres Suárez, Ana Isabel
Low drug loading, burst effect during release and drug inactivation account for the main drawbacks of protein microencapsulation in poly(d,l-lactic-co-glycolic) acid (PLGA) matrix by the water-in oil-in water (W/O/W) solvent evaporation method. Thus, the current study was set to invest the critical attributes of formulation and of elaboration process which determine protein loading into microparticles as well as its further release, using albumin as protein model. NaCl concentration in the external aqueous phase, poly(vinyl alcohol) (PVA) concentration and mostly viscosity of both the internal aqueous phase and the organic phase were critical attributes for improving drug loading, with polymer molecular weight and hydrophobicity likewise directly related to albumin loading. In such a way, when using 0.5% PVA as internal aqueous phase the highest albumin loading was achieved. Optimized microparticles exhibited a sustained in vitro release of albumin over 130 days. The influence of the microencapsulation process on albumin stability and biological activity was evaluated by carrying out cell proliferation assays on PC12 cells with albumin released from microparticles. Such assay demonstrated that the microencapsulation procedure optimized in this study did not affect the biological stability of the microencapsulated protein.
Overcoming Glucocorticoid Resistances and Improving Antitumor Therapies: Lipid and Polymers Carriers
(Pharmaceutical Research, 2014) Martín Sabroso, Cristina; Moreno-Ortega, A. J. ; Aparicio Blanco, Juan; Fraguas Sánchez, Ana Isabel; Cano-Abad, M. F. ; Torres Suárez, Ana Isabel
Purpose To improve chemotherapy protocols of lymphoid malignancies, by using polymeric and lipid microparticles as controlled delivery systems of dexamethasone, part of all combined chemotherapy protocols for its strong-inducing effect on malignant lymphoblasts. Methods Polymeric microparticles were prepared by the oil-in-water-emulsion cosolvent evaporation method, andlipid microparticles by spray drying. Their cytotoxic effects on GC-sensitive PC12 cells and GC-resistant PC3 cells were characterized by cell proliferation and apoptosis assays. Results Both elaboration methods rendered optimal-sized microparticles for parenteral administration with high drug loading. In vitro assays showed sustained dexamethasone release from polymeric microparticles over a month, whereas 100% dexamethasone release from lipid microparticles was achieved within 24 h. Similar PC12 cell death to that obtained with dexamethasone solution administered every 48 h was achieved with dexamethasone polymeric microparticles in 26-days assays. Dexamethasone solution and loaded polymeric microparticles induced apoptosis around 15.8 and 19.9%, respectively, after 2 days of incubation. Lipid microparticles increased further apoptosis induction in PC12 cells and, unlike dexamethasone solution and polymeric microparticles, showed antiproliferative effects on PC3 cells. Conclusions Dexamethasone polymeric microparticles constitute an alternative to current dexamethasone administration systems in combined chemotherapy, whereas dexamethasone lipid microparticles represent a potential tool to revert glucocorticoid resistance.
Cannabidiol Enhances the Passage of Lipid Nanocapsules across the Blood–Brain Barrier Both in Vitro and in Vivo
(Molecular Pharmaceutics, 2019) Aparicio Blanco, Juan; Romero, Ignacio A. ; Male, David K. ; Slowing Barillas, Karla Verónica; García-García, Luis ; Torres Suárez, Ana Isabel
Diseases affecting the central nervous system (CNS) should be regarded as a major health challenge due to the current lack of effective treatments given the hindrance to brain drug delivery imposed by the blood–brain barrier (BBB). Since efficient brain drug delivery should not solely rely on passive targeting, active targeting of nanomedicines into the CNS is being explored. The present study is devoted to the development of lipid nanocapsules (LNCs) decorated with nonpsychotropic cannabinoids as pioneering nonimmunogenic brain-targeting molecules and to the evaluation of their brain-targeting ability both in vitro and in vivo. Noticeably, both the permeability experiments across the hCMEC/D3 cell-based in vitro BBB model and the biodistribution experiments in mice consistently demonstrated that the highest brain-targeting ability was achieved with the smallest-sized cannabinoid-decorated LNCs. Importantly, the enhancement in brain targeting achieved with the conjugation of cannabidiol to LNCs outperformed by 6-fold the enhancement observed for the G-Technology (the main brain active strategy that has already entered clinical trials for the treatment of CNS diseases). As the transport efficiency across the BBB certainly determines the efficacy of the treatments for brain disorders, small cannabinoid-decorated LNCs represent auspicious platforms for the design and development of novel therapies for CNS diseases.
Limitations and Challenges in the Stability of Cysteamine Eye Drop Compounded Formulations
(Pharmaceuticals, 2022) Martín Sabroso, Cristina; Alonso González, Mario; Fernández Carballido, Ana María; Aparicio Blanco, Juan; Córdoba Díaz, Damián; Navarro García, Federico; Córdoba Díaz, Manuel; Torres Suárez, Ana Isabel
Accumulation of cystine crystals in the cornea of patients suffering from cystinosis is considered pathognomonic and can lead to severe ocular complications. Cysteamine eye drop compounded formulations, commonly prepared by hospital pharmacy services, are meant to diminish the build-up of corneal cystine crystals. The objective of this work was to analyze whether the shelf life proposed for six formulations prepared following different protocols used in hospital pharmacies is adequate to guarantee the quality and efficacy of cysteamine eye drops. The long-term and in-use stabilities of these preparations were studied using different parameters: content of cysteamine and its main degradation product cystamine; appearance, color and odor; pH and viscosity; and microbiological analysis. The results obtained show that degradation of cysteamine was between 20% and 50% after one month of storage in the long-term stability study and between 35% and 60% in the in-use study. These data confirm that cysteamine is a very unstable molecule in aqueous solution, the presence of oxygen being the main degradation factor. Saturation with nitrogen gas of the solutions offers a means of reducing cysteamine degradation. Overall, all the formulae studied presented high instability at the end of their shelf life, suggesting that their clinical efficacy might be dramatically compromised.
Project number: 85
Dinamización docente: las tutorías colectivas para optimizar la interacción profesor-alumno
(2017) Barcia Hernández, Emilia María; Negro Álvarez, María Sofía Elisa; Fernández Carballido, Ana María; Torres Suárez, Ana Isabel; Aparicio Blanco, Juan; Fraguas Sánchez, Ana Isabel
Las tutorías colectivas, presenciales y semipresenciales, constituyen un recurso docente muy valioso para optimizar la interacción profesor-alumno. Además fomentan la igualdad e inclusión de los alumnos al realizarse en grupos reducidos.
Project number: 410
Protocolo y herramientas para la virtualización de prácticas de laboratorio de materias de carácter tecnológico: aplicación en Tecnología Farmacéutica
(2021) Martín Sabroso, Cristina; Alonso González, Mario; Notivoli Díez, Pablo; Aparicio Blanco, Juan; Barcia Hernández, Emilia María; Córdoba Díaz, Manuel; Córdoba Díaz, Damián; Fernández Carballido, Ana María; García De Fernando Minguillón, Gonzalo Doroteo; Negro Álvarez, María Sofía Elisa; Torres Suárez, Ana Isabel
El proyecto se centra en la virtualización de prácticas que comprenden la elaboración y control de calidad de un producto, aplicándose a la elaboración y control de calidad de cápsulas y comprimidos, mediante el diseño, implementación y valoración de tres estrategias: videolecciones, proyectos y casos prácticos.
Project number: 211
Trivial-to-Learn: Aprendizaje basado en juegos en el área de conocimiento de Farmacia y Tecnología Farmacéutica (TRIVIALFAR)
() Fraguas Sánchez, Ana Isabel; Fernández Carballido, Ana María; García-Cremades Mira, María; Martín Sabroso, Cristina; Torres Suárez, Ana Isabel; Aparicio Blanco, Juan; Negro Álvarez, María Sofía Elisa; Barcia Hernández, Emilia María; Córdoba Díaz, Damián; Lozza, Irene; Gómez Lázaro, Laura; Pérez López, Alexandre; Gómez García, Víctor; Catalán Pallarés, Sandra; Rodriguez Sanchez, Rafael
La sociedad actual demanda a las Instituciones Educativas profesionales que tengan una formación integral que les permita adaptarse al entorno y a los requerimientos sociolaborales. Para ello, es esencial el empleo de metodologías docentes activas, como el aprendizaje basado en juegos, donde el estudiante es el protagonista del proceso de enseñanza-aprendizaje. El objetivo principal de este proyecto es diseñar y desarrollar juegos tipo Trivial como estrategia de aprendizaje activo en las asignaturas del área de conocimiento de Farmacia y Tecnología Farmacéutica. Concretamente se han desarrollado dos tipos de actividades: juegos tipo Trivial virtuales en la asignatura de Biofarmacia y Farmacocinética, y juegos tipo Trivial presenciales en las asignaturas de Productos Sanitarios y Tecnología Farmacéutica I. Ambas actividades han resultado ser una excelente herramienta de autoevaluación y repaso de los contenidos impartidos en la asignatura. Los juegos desarrollados en modalidad presencial fueron mejor evaluados por los alumnos que los desarrollados en modalidad virtual. Además, estos juegos presenciales les permitía adquirir competencias transversales, principalmente habilidades comunicativas, de liderazgo y de trabajo colaborativo.
Lipid nanocapsules decorated and loaded with cannabidiol as targeted prolonged release carriers for glioma therapy: In vitro screening of critical parameters
(European Journal of Pharmaceutics and Biopharmaceutics, 2019) Aparicio Blanco, Juan; Sebastián, Víctor ; Benoit, Jean P. ; Torres Suárez, Ana Isabel
The therapeutic potential of cannabinoids has been truly constrained heretofore due to their strong psychoactive effects and their high lipophilicity. In this context, precisely due to the lack of psychoactive properties, cannabidiol (CBD), the second major component of Cannabis sativa, arises as the phytocannabinoid with the most auspicious therapeutic potential. Hence, the incorporation of CBD in lipid nanocapsules (LNCs) will contribute to overcome the dosing problems associated with cannabinoids. Herein, we have prepared LNCs decorated and loaded with CBD for glioma therapy and screened in vitro their critical parameters. On the one hand, we have encapsulated CBD into the oily core of LNCs to test their in vitro efficacy as extended-release carriers against the human glioblastoma cell line U373MG. The in vitro antitumor effect was highly dependent on the size of LNCs due to its pivotal role in the extent of CBD release. Effectively, a comparison between two differently-sized LNCs (namely, 20-nm and 50-nm sized carriers) showed that the smaller LNCs reduced by 3.0-fold the IC50 value of their 50-nm sized counterparts. On the other hand, to explore the potential of this phytocannabinoid to target any of the cannabinoid receptors overexpressed in glioma cells, we decorated the LNCs with CBD. This functionalization strategy enhanced the in vitro glioma targeting by 3.4-fold in comparison with their equally-sized undecorated counterparts. Lastly, the combination of CBD-loading with CBD-functionalization further reduced the IC50 values. Hence, the potential of these two strategies of CBD incorporation into LNCs deserves subsequent in vivo evaluation.