Person:
Martín Sabroso, Cristina

First Name

Cristina

Last Name

Martín Sabroso

URI

https://hdl.handle.net/20.500.14352/77712

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 13

PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment
(Pharmaceutics, 2020) Fraguas Sánchez, Ana Isabel; Torres Suárez, Ana Isabel; Cohen, Marie; Delie, Florence; Bastida-Ruiz, Daniel; Yart, Lucile; Martín Sabroso, Cristina; Fernández Carballido, Ana María
The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy. Cannabidiol (CBD), the main nonpsychotropic cannabinoid, appears as a potential anticancer drug. The aim of this work was to develop polymer nanoparticles as CBD carriers capable of being internalised by ovarian cancer cells. The drug-loaded nanoparticles (CBD-NPs) exhibited a spherical shape, a particle size around 240 nm and a negative zeta potential (−16.6 ± 1.2 mV). The encapsulation efficiency was high, with values above 95%. A controlled CBD release for 96 h was achieved. Nanoparticle internalisation in SKOV 3 epithelial ovarian cancer cells mainly occurred between 2 and 4 h of incubation. CBD antiproliferative activity in ovarian cancer cells was preserved after encapsulation. In fact, CBD-NPs showed a lower IC50 values than CBD in solution. Both CBD in solution and CBD-NPs induced the expression of PARP, indicating the onset of apoptosis. In SKOV-3-derived tumours formed in the chick embryo model, a slightly higher—although not statistically significant tumour growth inhibition was observed with CBD-NPs compared to CBD in solution. To sum up, poly-lactic-co-glycolic acid (PLGA) nanoparticles could be a good strategy to deliver CBD intraperitoneally for ovarian cancer treatment.
Stability characteristics of cannabidiol for the design of pharmacological, biochemical and pharmaceutical studies
(Journal of chromatography B, 2020) Fraguas Sánchez, Ana Isabel; Fernández Carballido, Ana María; Martín Sabroso, Cristina; Torres Suárez, Ana Isabel
Cannabidiol (CBD) is one of the most promising cannabinoids in therapeutics. Nevertheless, the reported stability testing has been carried out with plant extracts and not with CBD as a drug substance. The aim of this work was to evaluate the stability of CBD in solution. A High-Performance Liquid Chromatography (HPLC) analytical method, with CBD in ethanol, was previously validated for these stability studies. The resulting method was linear and proportional in a range of concentrations from 1 to 150 µg CBD/mL, as well as precise. It was also considered suitable to quantify CBD in aqueous medium as reported in accuracy studies. The stability of CBD was influenced by multiple factors. Temperature was one of the most critical parameters, with an activation energy of 92.19KJ/mol. At room temperature, CBD was highly unstable (t95 = 117.13 days). However, at 5 °C it was stable for at least 12 months. CBD was also sensitive to oxidation, with a short t95 of 1.77 days in oxidizing environments, as well as to light. The photolytic reaction seems to be oxidative. The solvent influences CBD stability, and the latter is more stable in ethanol than in aqueous medium. In fact, in simulated physiological conditions (pH 7.4 and 37 °C) 10% of CBD was degraded within 24 h. These studies indicate that CBD is highly unstable, and this should be taken into account in the development of in vitro and in vivo studies of CBD activity and in the pharmaceutical development of dosage forms.
Enhancing ovarian cancer conventional chemotherapy through the combination with cannabidiol loaded microparticles
(European journal of pharmaceutics and biopharmaceutics, 2020) Fraguas Sánchez, Ana Isabel; Fernández Carballido, Ana María; Delie, F.; Cohen, M.; Martín Sabroso, Cristina; Mezzanzanica, D.; Figini, M.; Satta, A.; Torres Suárez, Ana Isabel
In this work, we evaluated, for the first time, the antitumor effect of cannabidiol (CBD) as monotherapy and in combination with conventional chemotherapeutics in ovarian cancer and developed PLGA-microparticles as CBD carriers to optimize its anticancer activity. Spherical microparticles, with a mean particle size around 25 µm and high entrapment efficiency were obtained. Microparticles elaborated with a CBD:polymer ratio of 10:100 were selected due to the most suitable release profile with a zero-order CBD release (14.13 ± 0.17 μg/day/10 mg Mps) for 40 days. The single administration of this formulation showed an in vitro extended antitumor activity for at least 10 days and an in ovo antitumor efficacy comparable to that of CBD in solution after daily topical administration (≈1.5-fold reduction in tumor growth vs control). The use of CBD in combination with paclitaxel (PTX) was really effective. The best treatment schedule was the pre + co-administration of CBD (10 µM) with PTX. Using this protocol, the single administration of microparticles was even more effective than the daily administration of CBD in solution, achieving a ≈10- and 8- fold reduction in PTX IC50 respectively. This protocol was also effective in ovo. While PTX conducted to a 1.5-fold tumor growth inhibition, its combination with both CBD in solution (daily administered) and 10-Mps (single administration) showed a 2-fold decrease. These results show the promising potential of CBD-Mps administered in combination with PTX for ovarian cancer treatment, since it would allow to reduce the administered dose of this antineoplastic drug maintaining the same efficacy and, as a consequence, reducing PTX adverse effects.
Current status of nanomedicine in the chemotherapy of breast cancer
(Cancer Chemotherapy and Pharmacology, 2019) Fraguas Sánchez, Ana Isabel; Martín Sabroso, Cristina; Fernández Carballido, Ana María; Torres Suárez, Ana Isabel
Despite the efforts that have been made in the field of breast cancer therapy, it is a leading cause of cancer death in women and a major health problem. The current treatments combine several strategies (surgery, radiotherapy, immunotherapy, hormone therapy, and chemotherapy) depending on cancer subtype and tumour stage. The use of chemotherapy is required in certain circumstances, like before or after surgery or in advanced stages of the disease. Chemotherapeutic regimens that include anthracyclines (e.g. doxorubicin), taxanes (e.g. paclitaxel), 5-fluorouracil and/or cyclophosphamide show, in general, a high toxicity that limit their clinical use. The use of targeted chemotherapy allows to get a selective location of the drug at tumour mass, decreasing the toxicity of these treatments. An increase of the antitumour efficacy can also be achieved. The use of nanocarriers containing anticancer drugs can be a good strategy to get targeted chemotherapy. In fact, several nanoformulations containing paclitaxel and doxorubicin have been approved or are under clinical trial for breast cancer therapy. The main advantage of these nanomedicines is their lower toxicity compared to conventional formulations, which can be attributed to the elimination of the solvents of the formulation (e.g. Cremophor-EL in paclitaxel conventional formulations) and the more selective location of the drug at tumour site (e.g. cardiotoxicity related to free doxorubicin). However, some adverse events (e.g. hand foot syndrome or infusion reactions) have been related to the administration of some nanomedicines, which have to be considered.
CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based chemotherapy in breast cancer
(International journal of pharmaceutics, 2019) Fraguas Sánchez, Ana Isabel; Fernández Carballido, Ana María; Simancas-Herbada, R.; Martín Sabroso, Cristina; Torres Suárez, Ana Isabel
Cannabidiol (CBD) has emerged as a potential agent for breast cancer management. In this work, the potential use of cannabidiol in solution (CBDsol) and encapsulated in polymeric microparticles when combined with paclitaxel (PTX) and doxorubicin (DOX) in breast cancer treatment has been evaluated for the first time using MCF-7 and MDA-MB-231 cells. CBDsol, previously administered at suboptimal concentrations (cell death < 10%), enhanced the PTX and DOX effect in both breast cancer cells. The co-administration of CBDsol and PTX or DOX showed a synergistic effect. PLGA-502 was selected as the most suitable polymer to develop CBD-loaded microparticles. The developed formulation (CBD-Mps) was effective as monotherapy, showing extended antiproliferative activity for at least 10 days, and when combined with PTX or DOX. In fact, the use of CBD-Mps allows the combination of both, pre and co-administration strategies, with a single administration, also showing a significant increase in PTX and DOX antiproliferative activity. Finally, the anticancer effect of both CBDsol and CBD-Mps as monotherapy or in combination with PTX was also confirmed in ovo, usingMDA-MB-231-derived tumours. This data evidences the promising inclusion of CBD in conventional breast cancer chemotherapy and the use of CBD-Mps for the extended release of this cannabinoid, optimising the effect of the chemotherapeutic agents.
DoE-based development of celecoxib loaded PLGA nanoparticles: In ovo assessment of its antiangiogenic effect
(European Journal of Pharmaceutics and Biopharmaceutics, 2022) Alonso González, Mario; Quispe Chauca, Prissila; Fernández Carballido, Ana María; Lozza, Irene; Martín Sabroso, Cristina; Fraguas Sánchez, Ana Isabel
Abnormal angiogenesis plays a main role in the pathogenesis of many diseases such as cancer, and inflammatory autoimmune disorders among others, and its inhibition represents a potential strategy for their management. Celecoxib (CXB) that is one of the most prescribed selective COX-2 inhibitors and is currently approved for the treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis inhibits angiogenesis. The objective of this manuscript was to design, develop, and characterize polymeric nanoparticles for the parenteral administration of CXB which the aim of facilitating its administration and improving its antiangiogenic activity while decreasing its adverse effects. A Plackett-Burman design was used to optimize the formulation. The PVA concentration, the sonication time, the sonicator amplitude and the CXB:PLGA ratio were selected as independent variables and particle size, polydispersity index, drug loading, and entrapment efficiency as responses. Optimized nanoparticles (formulations F2, F6 and F9) showed a particle size around 280 nm, a low polydispersion (PDI ≤ 0.2), a negative zeta potential around -25mV, a high entrapment efficiency (above 88%) and a controlled drug release for at least 10 days. Moreover, they were physically and chemically stable for at least 3 months when stored at 4°C. Interestingly, CXB-loaded nanoparticles showed a higher angiogenesis inhibition than CXB in solution administered at the same concentration. F9 nanoparticles that were prepared using PVA at 0.5%, a sonication time of 7 minutes, a sonicator amplitude of 80% and a CXB:PLGA ratio of 20:100 were selected as the most suitable CXB-formulation. It represents a promising strategy to administer CXB and improve its efficacy in disorders with pathological angiogenesis such as cancer and arthritic diseases.
Active Targeted Nanoformulations via Folate Receptors: State of the Art and Future Perspectives
(Pharmaceutics, 2021) Martín Sabroso, Cristina; Torres Suárez, Ana Isabel; Alonso-González, Mario; Fernández Carballido, Ana María; Fraguas Sánchez, Ana Isabel
In normal tissues, the expression of folate receptors is low and limited to cells that are important for embryonic development or for folate reabsorption. However, in several pathological conditions some cells, such as cancer cells and activated macrophages, overexpress folate receptors (FRs). This overexpression makes them a potential therapeutic target in the treatment of cancer and inflammatory diseases to obtain a selective delivery of drugs at altered cells level, and thus to improve the therapeutic efficacy and decrease the systemic toxicity of the pharmacological treatments. Two strategies have been used to achieve this folate receptor targeting: (i) the use of ligands with high affinity to FRs (e.g., folic acid or anti-FRs monoclonal antibodies) linked to the therapeutic agents or (ii) the use of nanocarriers whose surface is decorated with these ligands and in which the drug is encapsulated. This manuscript analyzes the use of FRs as a target to develop new therapeutic tools in the treatment of cancer and inflammatory diseases with an emphasis on the nanoformulations that have been developed for both therapeutic and imaging purposes.
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: PIMCD411/23-24
Integración de los Objetivos de Desarrollo Sostenible en la Docencia Universitaria. Aplicación en Farmacia y Tecnología Farmacéutica
(2024) García-Cremades Mira, María; Aparicio Blanco, Juan; Ayarzagüena Porras, Blanca; Barcia Hernández, Emilia María; Fernández Carballido, Ana María; Fraguas Sánchez, Ana Isabel; Martín Sabroso, Cristina; Negro Álvarez, María Sofía Elisa; Torres Suárez, Ana Isabel; Pérez López, Alexandre; Sánchez Prieto, Lucía; Gómez García, Víctor; Ortín Mira, Paloma
En 2015, los Estados miembros de las Naciones Unidas aprobaron 17 Objetivos de Desarrollo Sostenible (ODS) como parte de la Agenda 2030, abordando desafíos globales como la pobreza, salud, desigualdad, cambio climático, degradación ambiental y justicia. Este proyecto, enfocado en el área de Farmacia y Tecnología Farmacéutica, buscó integrar los ODS en la docencia universitaria para contribuir a un futuro más sostenible y justo.La idea principal era enfocar los conocimientos tratados en las diferentes asignaturas en la contribución a la consecución de las metas de los ODS, y que los estudiantes los identificaran, exploraran y aplicaran a través de trabajos individuales y colaborativos. El proyecto logró integrar satisfactoriamente los ODS en cursos de grado y posgrado, fomentando una educación inclusiva y comprometida. Se aplicaron específicamente el ODS 4 (Educación de Calidad) y el ODS 17 (Alianzas) mediante colaboraciones con ONG y otras facultades. Se llevaron a cabo seminarios y trabajos colaborativos en asignaturas como Biofarmacia y Farmacocinética (Grado en Farmacia), Tecnología Farmacéutica II (Grado en Farmacia), Tecnología Farmacéutica III (Grado en Farmacia), Productos Sanitarios (Grado en Farmacia), Investigación en Bioequivalencia y Medicamentos Genéricos (Máster en Farmacia y Tecnología Farmacéutica), Variabilidad y Cambio Climático (Máster en Meteorología y Geofísica). En dichos trabajos, los alumnos relacionaban los conocimientos adquiridos en las asignaturas, con los ODS. Además, la difusión del proyecto se logró a través de jornadas y presentaciones donde se mostraron los trabajos realizados por los estudiantes.
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.