Person: Martín Sabroso, Cristina
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First Name
Cristina
Last Name
Martín Sabroso
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Farmacia Galénica y Tecnología Alimentaria
Area
Farmacia y Tecnología Farmaceútica
Identifiers
6 results
Search Results
Now showing 1 - 6 of 6
Item 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 IsabelDespite 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.Item Desarrollo de micropartículas de dexametasona como estrategia para aumentar la eficacia de los esquemas de poliquimioterapia(2014) Martín Sabroso, Cristina; Torres Suárez, Ana IsabelGlucocorticoids (GCs) and dexamethasone play a central role in the treatment of lymphoid malignancies, particularly acute lymphoblastic leukaemia (ALL). Preclinical studies have shown that GCs also affect cell differentiation, proliferation and apoptosis of osteosarcoma cells, hepatoma cells, mammary tumor cells, glioma cells, melanoma cells and thyroid cancer cells. The proliferation and apoptotic effects of GCs are cell type-specific as well as time and concentration dependent. In spite of the high effectiveness of dexamethasone treatment in ALL, mainly in children, GC resistance occurs in 10-30% of untreated patients, being more frequent in T-lineage than B-precursor acute lymphoblastic leukaemia. Furthermore, systemic administration of high doses of dexamethasone are required for inducing tumor cell apoptosis but causes severe side effects such as osteoporosis, Cushing's syndrome or an increased risk of infections. Even though most combined chemotherapy protocols currently used in clinics include dexamethasone at high doses, recent clinical investigations on the eficacy of dexamethasone in refractory multiple myeloma have shown synergic effects of low doses of this GC combined with pomalidomide or lenalidomide...Item 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 IsabelLow 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.Item 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 IsabelPurpose 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.Item In vitro screening of nanomedicines through the blood brain barrier: A critical review(Biomaterials, 2016) Aparicio Blanco, Juan; Martín Sabroso, Cristina; Torres Suárez, Ana IsabelThe blood-brain barrier accounts for the high attrition rate of the treatments of most brain disorders, which therefore remain one of the greatest health-care challenges of the twenty first century. Against this background of hindrance to brain delivery, nanomedicine takes advantage of the assembly at the nanoscale of available biomaterials to provide a delivery platform with potential to raising brain levels of either imaging or therapeutic agents. Nevertheless, to prevent later failure due to ineffective drug levels at the target site, researchers have been endeavoring to develop a battery of in vitro screening procedures that can predict earlier in the drug discovery process the ability of these cutting-edge drug delivery platforms to cross the blood-brain barrier for biomedical purposes. This review provides an in-depth analysis of the currently available in vitro blood-brain barrier models (both cell-based and non-cell-based) with the focus on their suitability for understanding the biological brain distribution of forthcoming nanomedicines. The relationship between experimental factors and underlying physiological assumptions that would ultimately lead to a more predictive capacity of their in vivo performance, and those methods already assayed for the evaluation of the brain distribution of nanomedicines are comprehensively discussed.Item 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 IsabelCannabidiol (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.