Person: Ballesteros Papantonakis, María De La Paloma
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First Name
María De La Paloma
Last Name
Ballesteros Papantonakis
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Farmacia Galénica y Tecnología Alimentaria
Area
Farmacia y Tecnología Farmaceútica
Identifiers
15 results
Search Results
Now showing 1 - 10 of 15
Item Transferosomes as nanocarriers for drugs across the skin: Quality by design from lab to industrial scale(International Journal of Pharmaceutics, 2021) Fernández-García, Raquel; Lalatsa, Aikaterini; Statts, Larry; Bolas Fernández, Francisco; Ballesteros Papantonakis, María De La Paloma; Serrano López, Dolores RemediosTransferosomes, also known as transfersomes, are ultradeformable vesicles for transdermal applications consisting of a lipid bilayer with phospholipids and an edge activator and an ethanol/aqueous core. Depending on the lipophilicity of the active substance, it can be encapsulated within the core or amongst the lipid bilayer. Compared to liposomes, transferosomes are able to reach intact deeper regions of the skin after topical administration delivering higher concentrations of active substances making them a successful drug delivery carrier for transdermal applications. Most transferosomes contain phosphatidylcholine (C18) as it is the most abundant lipid component of the cell membrane, and hence, it is highly tolerated for the skin, decreasing the risk of undesirable effects, such as hypersensitive reactions. The most common edge activators are surfactants such as sodium deoxycholate, Tween® 80 and Span® 80. Their chain length is optimal for intercalation within the C18 phospholipid bilayer. A wide variety of drugs has been successfully encapsulated within transferosomes such as phytocompounds like sinomenine or apigenin for rheumatoid arthritis and leukaemia respectively, small hydrophobic drugs but also macromolecules like insulin. The main factors to develop optimal transferosomal formulations (with high drug loading and nanometric size) are the optimal ratio between the main components as well as the critical process parameters for their manufacture. Application of quality by design (QbD), specifically design of experiments (DoE), is crucial to understand the interplay among all these factors not only during the preparation at lab scale but also in the scale-up process. Clinical trials of a licensed topical ketoprofen transferosomal gel have shown promising results in the alleviation of symptons in orthreothritis with non-severe skin and subcutaneous tissue disorders. However, the product was withdrawn from the market which probably was related to the higher cost of the medicine linked to the expensive manufacturing process required in the production of transferosomes compared to other conventional gel formulations. This example brings out the need for a careful formulation design to exploit the best properties of this drug delivery system as well as the development of manufacturing processes easily scalable at industrial level.- Project number: PIMCD340/23-24
Item 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, SusanaEl 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. Item Self-assembling, supramolecular chemistry and pharmacology of amphotericin B: Poly-aggregates, oligomers and monomers(Journal of Controlled Release, 2021) Raquel Fernández-García; Juan C. Muñoz-García; Matthew Wallace; Laszlo Fabian; González Burgos, Elena María; Gómez-Serranillos Cuadrado, María Pilar; Raposo González, Rafaela; Bolas Fernández, Francisco; Ballesteros Papantonakis, María De La Paloma; Anne Marie Healy; Yaroslav Z. Khimyak; Serrano López, Dolores RemediosAntifungal drugs such as amphotericin B (AmB) interact with lipids and phospholipids located on fungal cell membranes to disrupt them and create pores, leading to cell apoptosis and therefore efficacy. At the same time, the interaction can also take place with cell components from mammalian cells, leading to toxicity. AmB was selected as a model antifungal drug due to the complexity of its supramolecular chemical structure which can self-assemble in three different aggregation states in aqueous media: monomer, oligomer (also known as dimer) and poly-aggregate. The interplay between AmB self-assembly and its efficacy or toxicity against fungal or mammalian cells is not yet fully understood. To the best of our knowledge, this is the first report that investigates the role of excipients in the supramolecular chemistry of AmB and the impact on its biological activity and toxicity. The monomeric state was obtained by complexation with cyclodextrins resulting in the most toxic state, which was attributed to the greater production of highly reactive oxygen species upon disruption of mammalian cell membranes, a less specific mechanism of action compared to the binding to the ergosterol located in fungal cell membranes. The interaction between AmB and sodium deoxycholate resulted in the oligomeric and polyaggregated forms which bound more selectively to the ergosterol of fungal cell membranes. NMR combined with XRD studies elucidated the interaction between drug and excipient to achieve the AmB aggregation states, and ultimately, their diffusivity across membranes. A linear correlation between particle size and the efficacy/toxicity ratio was established allowing to modulate the biological effect of the drug and hence, to improve pharmacological regimens. However, particle size is not the only factor modulating the biological response but also the equilibrium of each state which dictates the fraction of free monomeric form available. Tuning the aggregation state of AmB formulations is a promising strategy to trigger a more selective response against fungal cells and to reduce the toxicity in mammalian cells.Item Can Amphotericin B and Itraconazole be co-delivered orally? Tailoring Oral Fixed-Dose Combination Coated Granules for Systemic Mycoses(European Journal of Pharmaceutics and Biopharmaceutics, 2023) Fernández García, Raquel; Walsh, David; O'Connell, Peter; Slowing Barillas, Karla Verónica; Raposo González, Rafaela; Ballesteros Papantonakis, María De La Paloma; JImenez-Cebrian, Aurora; Chamorro Sancho, Manuel J.; Bolas Fernández, Francisco; Healy, Anne Marie; Serrano López, Dolores RemediosThe incidence and prevalence of invasive fungal infections have increased significantly over the last few years, leading to a global health problem due to the lack of effective treatments. Amphotericin B (AmB) and itraconazole (ITR) are two antifungal drugs with different mechanisms of action. In this work, AmB and ITR have been formulated within granules to elicit an enhanced pharmacological effect, while enhancing the oral bioavailability of AmB. A Quality by Design (QbD) approach was utilised to prepare fixed-dose combination (FDC) granules consisting of a core containing AmB with functional excipients, such as inulin, microcrystalline cellulose (MCC), chitosan, sodium deoxycholate (NaDC) and Soluplus® and polyvinyl pyrrolidone (PVP), coated with a polymeric layer containing ITR with Soluplus® or a combination of Poloxamer 188 and hydroxypropyl methyl cellulose-acetyl succinate (HPMCAS). A Taguchi designs of experiments (DoE) with 7 factors and 2 levels was carried out to understand the key factors impacting on the physicochemical properties of the formulation followed by a Box-Behnken design with 3 factors in 3 levels chosen to optimise the formulation parameters. The core of the FDC granules was obtained by wet granulation and later coated using a fluidized bed. In vitro antifungal efficacy was demonstrated by measuring the inhibition halo against different species of Candida spp., including C. albicans (24.19-30.48 mm), C. parapsilosis (26.38-27.84 mm) and C. krusei (11.48-17.92 mm. AmB release was prolonged from 3 to 24 hours when the AmB granules were coated. In vivo in CD-1 male mice studies showed that these granules were more selective towards liver, spleen and lung compared to kidney (up to 5-fold more selective in liver, with an accumulation of 8.07 µg AmB/g liver after twice-daily 5 days administration of F2), resulting in an excellent oral administration option in the treatment of invasive mycosis. Nevertheless, some biochemical alterations were found, including a decrease in blood urea nitrogen (~17 g/dl) and alanine aminotransferase (<30 U/l) and an increase in the levels of bilirubin (~0.2 mg/dl) and alkaline phosphatase (<80 U/l), which could be indicative of a liver failure. Once-daily regimen for 10 days can be a promising therapy.- Project number: 291
Item 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 LaCreación 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. Item Engineering of 3D printed personalized polypills for the treatment of the metabolic syndrome(International Journal of Pharmaceutics, 2023) Anaya, Brayan J.; Cerda, Jose R.; D'Atri, Rita; Yuste, Iván; Luciano, Francis C.; Kara, Aytug; Ruiz Saldaña, Helga Karina; Ballesteros Papantonakis, María De La Paloma; Serrano López, Dolores RemediosMetabolic syndrome is a collection of abnormalities, including at least three of the following insulin resistance, hypertension, dyslipidemia, type 2 diabetes, obesity, inflammation, and non-alcoholic fatty liver disease. 3D printed solid dosage forms have emerged as a promising tool enabling the fabrication of personalized medicines and offering solutions that cannot be achieved by industrial mass production. Most attempts found in the literature to manufacture polypills for this syndrome contain just two drugs. However, most fixed-dose combination (FDC) products in clinical practice required the use of three or more drugs. In this work, Fused deposition modelling (FDM) 3D printing technology coupled with Hot-melt extrusion (HME) has been successfully applied in the manufacture of polypills containing nifedipine (NFD), as an antihypertensive drug, simvastatin (SMV), as an antihyperlipidemic drug, and gliclazide (GLZ) as an antiglycemic drug. Hanssen solubility parameters (HSPs) were utilized as predictors to guide the formation of amorphous solid dispersion between drug and polymer to ensure miscibility and enhanced oral bioavailability. The HSP varied from 18.3 for NFD, 24.6 for SMV, and 7.0 for GLZ while the total solubility parameter for the excipient mixture was 27.30.5. This allowed the formation of an amorphous solid dispersion in SMV and GLZ 3D printed tablets compared to NFD which was partially crystalline. Popypill showed a dual release profile combining a faster SMV release (< 6 h) with a 24 h sustained release for NDF and GLZ. This work demonstrated the transformation of FDC into dynamic dose-personalized polypills.Item Ultradeformable Lipid Vesicles Localize Amphotericin B in the Dermis for the Treatment of Infectious Skin Diseases(ACS Infectious diseases, 2020) Fernández García, Raquel; Statts, Larry; Jesus, Jéssica A. De; Dea-Ayuela, María Auxiliadora; Bautista Chávez, Liliana; Simão, Rubén; Bolas Fernández, Francisco; Ballesteros Papantonakis, María De La Paloma; Laurenti, Marcia Dalastra; Passero, Luiz F. D.; Lalatsa, Aikaterini; Serrano López, Dolores RemediosCutaneous fungal and parasitic diseases remain challenging to treat, as available therapies are unable to permeate the skin barrier. Thus, treatment options rely on systemic therapy,which fail to produce high local drug concentrations but can lead tosignificant systemic toxicity. Amphotericin B (AmB) is highly efficacious in the treatment of both fungal and parasitic diseases such as cutaneous leishmaniasis but is reserved for parenteraladministration in patients with severe pathophysiology. Here, we have designed and optimized AmB-transfersomes [93.5% encapsulationefficiency, 150 nm size, and good colloidal stability (−35.02mV)] that can remain physicochemically stable (>90% drug content)at room temperature and 4 °C over 6 months when lyophilized and stored under desiccated conditions. AmB-transfersomes possessed good permeability across mouse skin (4.91 ± 0.41 μg/cm2/h) and 10-fold higher permeability across synthetic Strat-M membranes. In vivo studies after a single topical application in mice showed permeability and accumulation within the dermis (>25 μg AmB/g skin 6 h postadministration), indicating the delivery of therapeutic amounts of AmB for mycoses and cutaneous leishmaniasis, while a single daily administration in Leishmania (Leishmania) amazonensis infected mice over 10 days, resulted in excellent efficacy (98% reduction in Leishmania parasites). Combining the application of AmB-transfersomes with metallic microneedles in vivo increased the levels in the SC and dermis but was unlikely to elicit transdermal levels. In conclusion, AmB-transfersomes are promising and stable topical nanomedicines that can be readily translated for parasitic and fungal infectious diseases.- Project number: 254
Item 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 - Project number: 60
Item Creación de nuevos recursos educativos virtuales para estudiantes de grado en Farmacia(2022) Torrado Durán, Susana; Ballesteros Papantonakis, María De La Paloma; Torrado Durán, Juan José; Álvarez Álvarez, Covadonga; Torrado Durán, Santiago; Martínez Caballero, Marta; Torrado Durán, Guillermo; Martínez Caballero, María Aranzazu; Franco Gil, Elvira; Sastre Barbas, Almudena; Rodríguez Torrado, Marta; Torrado Salmerón, Carlos Félix; Torre Iglesias, Paloma Marina De La; Rodríguez Torrado, David; Ares Lombán, Irma; Fernández Gutierrez, Jesús Miguel; Franco Gil, María Elvira Item Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers(International journal of pharmaceutics, 2023) de Pablo, E; O'Connell, Peter; Fernández García, Raquel; Marchand, Sandrine; Chauzy, A.; Tewes, F; Dea Ayuela, María Auxiliadora; Kumar, D.; Bolas Fernández, Francisco; Ballesteros Papantonakis, María De La Paloma; Torrado Durán, Juan José; Healy, Anne Marie; Serrano López, Dolores RemediosThe incidence of fungal pulmonary infections is known to be on the increase, and yet there is an alarming gap in terms of marketed antifungal therapies that are available for pulmonary administration. Amphotericin B (AmB) is a highly efficient broad-spectrum antifungal only marketed as an intravenous formulation. Based on the lack of effective antifungal and antiparasitic pulmonary treatments, the aim of this study was to develop a carbohydrate-based AmB dry powder inhaler (DPI) formulation, prepared by spray drying. Amorphous AmB microparticles were developed by combining 39.7% AmB with 39.7% γ-cyclodextrin, 8.1% mannose and 12.5% leucine. An increase in the mannose concentration from 8.1 to 29.8%, led to partial drug crystallisation. Both formulations showed good in vitro lung deposition characteristics (80% FPF< 5 µm and MMAD < 3 µm) at different air flow rates (60 and 30 L/min) when used with a DPI, but also during nebulisation upon reconstitution in water.