Person:
Serrano López, Dolores Remedios

First Name

Dolores Remedios

Last Name

Serrano López

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Farmacia Galénica y Tecnología Alimentaria

Area

Farmacia y Tecnología Farmaceútica

Identifiers

Full item page

Search Results

Now showing 1 - 10 of 28

Evaluating the Potential of Ursolic Acid as Bioproduct for Cutaneous and Visceral Leishmaniasis
(MDPI, 2020-03-19) Bilbao Ramos, Pablo Estanislao; Serrano López, Dolores Remedios; Ruiz Saldaña, Helga Karina; Torrado Durán, Juan José; Bolás 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.
Creación de nuevo recurso educativo virtual para estudiantes de grado en Farmacia
(2020-07-07) 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 Felix; Rodríguez Torrado, Marta; Fernández Gutiérrez, Jesús Miguel; Rodríguez Torrado, David; Notivoli Díez, Pablo; Franco Gil, María Elvira
Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis
(MDPI, 2019-07-20) Bezerra-Souza, Adriana; Fernandez-Garcia, Raquel; Rodrigues, Gabriela F.; Bolás Fernández, Francisco; Dalastra Laurenti, Marcia; Passero, Luiz Felipe; Lalatsa, Aikaterini; Serrano López, Dolores Remedios
Leishmaniasis is a neglected tropical disease a_ecting more than 12 million people worldwide, which in its visceral clinical form (VL) is characterised by the accumulation of parasites in the liver and spleen, and can lead to death if not treated. Available treatments are not well tolerated due to severe adverse e_ects, need for parenteral administration and patient hospitalisation, and long duration of expensive treatments. These treatment realities justify the search for new e_ective drugs, repurposing existing licensed drugs towards safer and non-invasive cost-e_ective medicines for VL. In this work, we provide proof of concept studies of butenafine and butenafine self-nanoemulsifying drug delivery systems (B-SNEDDS) against Leishmania infantum. Liquid B-SNEDDS were optimised using design of experiments, and then were spray-dried onto porous colloidal silica carriers to produce solid-B-SNEDDS with enhanced flow properties and drug stability. Optimal liquid B-SNEDDS consisted of Butenafine:Capryol 90:Peceol:Labrasol (3:49.5:24.2:23.3 w/w), which were then sprayed-dried with Aerosil 200 with a final 1:2 (Aerosil:liquid B-SNEDDS w/w) ratio. Spray-dried particles exhibited near-maximal drug loading, while maintaining excellent powder flow properties (angle of repose <10_) and sustained release in acidic gastrointestinal media. Solid-B-SNEDDS demonstrated greater selectivity index against promastigotes and L. infantum-infected amastigotes than butenafine alone. Developed oral solid nanomedicines enable the non-invasive and safe administration of butenafine as a cost-e_ective and readily scalable repurposed medicine for VL.
Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers
(Elsevier, 2023-03-25) de Pablo, E; O'Connell, Peter; Fernández García, Raquel; Marchand, Sandrine; Chauzy, A.; Tewes, F; Dea Ayuela, María Auxiliadora; Kumar, D.; Bolás Fernández, Francisco; Ballesteros Papantonakis, Paloma; Torrado Durán, Juan José; Healy, Anne Marie; Serrano López, Dolores Remedios
The 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.
Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms
(MDPI, 2020-04-11) Cerda, Jose R.; Arifi, Talaya; Ayyoubi, Sejad; Knief, Peter; Ballesteros Papantonakis, María de la Paloma; Keeble, William; Barbu, Eugen; Healy, Anne Marie; Lalatsa, Aikaterini; Serrano López, Dolores Remedios
Although not readily accessible yet to many community and hospital pharmacists, fuse deposition modelling (FDM) is a 3D printing technique that can be used to create a 3D pharmaceutical dosage form by employing drug loaded filaments extruded via a nozzle, melted and deposited layer by layer. FDM requires printable filaments, which are commonly manufactured by hot melt extrusion, and identifying a suitable extrudable drug-excipient mixture can sometimes be challenging. We propose here the use of passive diffusion as an accessible loading method for filaments that can be printed using FDM technology to allow for the fabrication of oral personalised medicines in clinical settings. Utilising Hansen Solubility Parameters (HSP) and the concept of HSP distances (Ra) between drug, solvent, and filament, we have developed a facile pre-screening tool for the selection of the optimal combination that can provide a high drug loading (a high solvent-drug Ra, >10, and an intermediate solvent filament Ra value, ~10). We have identified that other parameters such as surface roughness and stiffness also play a key role in enhancing passive diffusion of the drug into the filaments. A predictive model for drug loading was developed based on Support Vector Machine (SVM) regression and indicated a strong correlation between both Ra and filament stiffness and the diffusion capacity of a model BCS Class II drug, nifedipine (NFD), into the filaments. A drug loading, close to 3% w/w, was achieved. 3D printed tablets prepared using a PVA-derived filament (Hydrosupport, 3D Fuel) showed promising characteristics in terms of dissolution (with a sustained release over 24 h) and predicted chemical stability (>3 years at 25 ◦C/60% relative humidity), similar to commercially available NFD oral dosage forms. We believe FDM coupled with passive diffusion could be implemented easily in clinical settings for the manufacture of tailored personalised medicines, which can be stored over long periods of time (similar to industrially manufactured solid dosage forms).
Engineering of 3D printed personalized polypills for the treatment of the metabolic syndrome
(Elsevier, 2023-06-30) 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 Remedios
Metabolic 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.
Personalised 3D Printed Medicines: Which Techniques and Polymers Are More Successful?
(MDPI, 2017-09-22) Konta, Andrea Alice; García Piña, Marta; Serrano López, Dolores Remedios
The interindividual variability is an increasingly global problem when treating patients from different backgrounds with diverse customs, metabolism, and necessities. Dose adjustment is frequently based on empirical methods, and therefore, the chance of undesirable side effects to occur is high. Three-dimensional (3D) Printed medicines are revolutionsing the pharmaceutical market as potential tools to achieve personalised treatments adapted to the specific requirements of each patient, taking into account their age, weight, comorbidities, pharmacogenetic, and pharmacokinetic characteristics. Additive manufacturing or 3D printing consists of a wide range of techniques classified in many categories but only three of them are mostly used in the 3D printing of medicines: printing-based inkjet systems, nozzle-based deposition systems, and laser-based writing systems. There are several drawbacks when using each technique and also the type of polymers readily available do not always possess the optimal properties for every drug. The aim of this review is to give an overview about the current techniques employed in 3D printing medicines, highlighting their advantages, disadvantages, along with the polymer and drug requirements for a successful printing. The major application of these techniques will be also discussed.
Understanding Direct Powder Extrusion for Fabrication of 3D Printed Personalised Medicines: A Case Study for Nifedipine Minitablets
(MDPI, 2021-09-29) Sánchez Guirales, Sergio A.; Jurado, Noelia; Kara, Aytug; Lalatsa, Aikaterini; Serrano López, Dolores Remedios
Fuse deposition modelling (FDM) has emerged as a novel technology for manufacturing 3D printed medicines. However, it is a two-step process requiring the fabrication of filaments using a hot melt extruder with suitable properties prior to printing taking place, which can be a rate-limiting step in its application into clinical practice. Direct powder extrusion can overcome the difficulties encountered with fabrication of pharmaceutical-quality filaments for FDM, allowing the manufacturing, in a single step, of 3D printed solid dosage forms. In this study, we demonstrate the manufacturing of small-weight (<100 mg) solid dosage forms with high drug loading (25%) that can be easily undertaken by healthcare professionals to treat hypertension. 3D printed nifedipine minitablets containing 20 mg were manufactured by direct powder extrusion combining 15% polyethylene glycol 4000 Da, 40% hydroxypropyl cellulose, 19% hydroxy propyl methyl cellulose acetate succinate, and 1% magnesium stearate. The fabricated 3D printed minitablets of small overall weight did not disintegrate during dissolution and allowed for controlled drug release over 24 h, based on erosion. This release profile of the printed minitablets is more suitable for hypertensive patients than immediate-release tablets that can lead to a marked burst effect, triggering hypotension. The small size of the minitablet allows it to fit inside of a 0-size capsule and be combined with other minitablets, of other API, for the treatment of complex diseases requiring polypharmacy within a single dosage form.
Antifungal and Antiparasitic Drug Delivery
(MDPI, 2020-04-04) 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”.
Development of Advanced 3D-Printed Solid Dosage Pediatric Formulations for HIV Treatment
(MPDI, 2022-03-31) Malebari, Azizah M.; Kara, Aytug; Khayyat, Ahdab N.; Mohammad, Khadijah A.; Serrano López, Dolores Remedios
The combination of lopinavir/ritonavir remains one of the first-line therapies for the initial antiretroviral regimen in pediatric HIV-infected children. However, the implementation of this recommendation has faced many challenges due to cold-chain requirements, high alcohol content, and unpalatability for ritonavir-boosted lopinavir syrup. In addition, the administration of crushed tablets has shown a detriment for the oral bioavailability of both drugs. Therefore, there is a clinical need to develop safer and better formulations adapted to children’s needs. This work has demonstrated, for the first time, the feasibility of using direct powder extrusion 3D printing to manufacture personalized pediatric HIV dosage forms based on 6 mm spherical tablets. H-bonding between drugs and excipients (hydroxypropyl methylcellulose and polyethylene glycol) resulted in the formation of amorphous solid dispersions with a zero-order sustained release profile, opposite to the commercially available formulation Kaletra, which exhibited marked drug precipitation at the intestinal pH.