Francisca Villanueva-Flores

Dr. Francisca Villanueva-Flores

orcid

Research Focus & Metrics

Academic Career Length

8Years (2019-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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30 August 2025 in npj Vaccines
Verified
Journal Article
Open access
PDF file
FVFrancisca Villanueva-Flores
Francisca Villanueva-Flores
JSJavier Sanchez-Villamil
Javier Sanchez-Villamil
Igor Garcia-AtutxaIgor Garcia-Atutxa
Igor Garcia-Atutxa
Integrating AI into epitope prediction is transforming vaccine design by delivering unprecedented accuracy, speed, and efficiency. This review synthesizes recent breakthroughs particularly CNNs, transformers, and GNNs highlighting experimentally validated models like MUNIS and GraphBepi that reveal previously overlooked epitopes. By benchmarking AI tools against traditional methods, we identify structural data integration as pivotal, offering practical strategies to translate computational predictions into actionable experimental workflows for next-generation vaccines.

16 June 2023 in Pharmaceutics
Verified
Journal Article
Open access
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FVFrancisca Villanueva-Flores
Francisca Villanueva-Flores
Igor Garcia-AtutxaIgor Garcia-Atutxa
Igor Garcia-Atutxa
ASArturo Santos
Arturo Santos
JAJuan Armendariz-Borunda
Juan Armendariz-Borunda
Neural tissue engineering presents a compelling technological breakthrough in restoring brain function, holding immense promise. However, the quest to develop implantable scaffolds for neural culture that fulfill all necessary criteria poses a remarkable challenge for material science. These materials must possess a host of desirable characteristics, including support for cellular survival, proliferation, and neuronal migration and the minimization of inflammatory responses. Moreover, they should facilitate electrochemical cell communication, display mechanical properties akin to the brain, emulate the intricate architecture of the extracellular matrix, and ideally allow the controlled release of substances. This comprehensive review delves into the primary requisites, limitations, and prospective avenues for scaffold design in brain tissue engineering. By offering a panoramic overview, our work aims to serve as an essential resource, guiding the creation of materials endowed with bio-mimetic properties, ultimately revolutionizing the treatment of neurological disorders by developing brain-implantable scaffolds.
1

6 September 2025 in Pharmaceutics
Verified
Journal Article
Open access
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LNLucio Nájera-Maldonado
Lucio Nájera-Maldonado
MPMariana Parra-González
Mariana Parra-González
MCMaría Esperanza Peralta Cuevas
María Esperanza Peralta Cuevas
AGAshley J. Gutierrez-Onofre
Ashley J. Gutierrez-Onofre
Igor Garcia-AtutxaIgor Garcia-Atutxa
Igor Garcia-Atutxa
FVFrancisca Villanueva-Flores
Francisca Villanueva-Flores
This review provides a mechanistic framework to strategically design nanoparticles capable of efficiently crossing the blood–brain barrier (BBB), a critical limitation in neurological treatments. We systematically analyze nanoparticle–BBB transport mechanisms, including receptor-mediated transcytosis, adsorptive-mediated transcytosis, and transient barrier modulation. Essential nanoparticle parameters (size, shape, stiffness, surface charge, and biofunctionalization) are evaluated for their role in enhancing brain targeting. For instance, receptor-targeted nanoparticles can significantly enhance brain uptake, achieving levels of up to 17.2% injected dose per gram (ID/g) in preclinical glioma models. Additionally, validated preclinical models (human-derived in vitro systems, rodents, and non-human primates) and advanced imaging techniques crucial for assessing nanoparticle performance are discussed. Distinct from prior BBB nanocarrier reviews that primarily catalogue mechanisms, this work (i) derives quantitative ‘design windows’ (size 10–100 nm, aspect ratio ~2–5, near-neutral ζ) linked to transcytosis efficiency, (ii) cross-walks human-relevant in vitro/in vivo models (including TEER thresholds and NHP evidence) into a translational decision guide, and (iii) integrates regulatory/toxicology readiness (ISO 10993-4, FDA/EMA, ICH) into practical checklists. We also curate recent (2020–2025) %ID/g brain-uptake data across lipidic, polymeric, protein, inorganic, and hybrid vectors to provide actionable, evidence-based rules for BBB design.

11 October 2024 in Frontiers in Immunology
Verified
Journal Article
Open access
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Igor Garcia-AtutxaIgor Garcia-Atutxa
Igor Garcia-Atutxa
PMPaul Mondragon-Teran
Paul Mondragon-Teran
AHAlejandro Huerta-Saquero
Alejandro Huerta-Saquero
FVFrancisca Villanueva-Flores
Francisca Villanueva-Flores
Monkeypox (mpox) is a zoonotic illness caused by the monkeypox virus (MPXV), with higher health concerns among people who are pregnant, children, and persons who are immunocompromised, including people with untreated and advanced HIV disease. Significant progress has been made in developing vaccines against mpox, yet critical challenges and limitations persist in ensuring their effectiveness, safety, and accessibility. The pertinence of this review is highlighted by the World Health Organization’s declaration of a global health emergency on August 14, 2024, due to the recent mpox outbreak, underscoring the critical necessity for effective vaccine solutions in the face of a rapidly evolving virus. Here, we comprehensively analyze various vaccine platforms utilized in mpox prevention, including attenuated and non-replicating virus vaccines, viral vector-based vaccines, recombinant protein vaccines, and DNA and mRNA vaccines. We evaluate the advantages and limitations of each platform, highlighting the urgent need for ongoing research and innovation to enhance vaccine efficacy and safety. Recent advancements, such as incorporating immunostimulatory sequences, improved delivery systems, and developing polyvalent vaccines, are explored for their potential to offer broader protection against diverse orthopoxvirus strains. This work underscores the need to optimize currently available vaccines and investigate novel vaccination strategies to address future public health emergencies effectively. By focusing on these advanced methodologies, we aim to contribute to the development of robust and adaptable vaccine solutions for mpox and other related viral threats.
1

10 February 2026 in Frontiers in Pharmacology
Verified
Journal Article
Open access
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EPEsperanza Peralta-Cuevas
Esperanza Peralta-Cuevas
NDNahomi Y. Degollado-Hernández
Nahomi Y. Degollado-Hernández
IMIliana C. Martínez-Ortiz
Iliana C. Martínez-Ortiz
AGAshley J. Gutierrez-Onofre
Ashley J. Gutierrez-Onofre
Igor Garcia-AtutxaIgor Garcia-Atutxa
Igor Garcia-Atutxa
FVFrancisca Villanueva-Flores
Francisca Villanueva-Flores
Many therapeutics fail due to suboptimal pharmacokinetics/pharmacodynamics (PK/PD), and the development of nanomedicine remains partly empirical. We present a protocol-guided, mechanistic review that links nanoparticle (NP) physicochemical traits (such as size, surface charge/hydrophobicity, elasticity, and composition) to protein-corona remodeling, immune recognition, biodistribution, and clearance across the ADME, and examines how these shifts translate into pharmacodynamics and therapeutic index. We systematically searched PubMed, Web of Science, Scopus, and ClinicalTrials.gov (primarily 2000–2025) using predefined Boolean strings. We included in vivo animal or human studies directly comparing the same drug in NP versus non-NP formulations with matched route and comparable dose, reporting at least one PK and/or PD endpoint, while excluding in vitro-only reports, reviews/opinion articles, and studies with undisclosed or non-comparable vehicles. We curated in vivo , route-matched comparisons of the same drug in NP versus non-NP forms and compiled an eight-drug cross-compound dataset. Where variance permitted, we quantified effects using standardized ln-ratios for AUC, half-life, and clearance, and flagged vehicle-matched comparisons to avoid overattributing gains to nanoscale architecture. Across oral and intravenous delivery, NPs consistently increased systemic exposure and prolonged half-life, with the most significant benefits in poorly soluble, lipophilic molecules; effect sizes were context-dependent and, in some formulations, reached multi-fold improvements. Mechanistically, we delineate when lymphatic uptake (long-chain lipid carriers), receptor-mediated transcytosis (e.g., BBB-oriented designs), or context-limited EPR are most contributory, and we highlight stiffness-dependent corona effects (e.g., ApoA-I enrichment) as a lever to extend circulation. To enable translation, we contribute: (i) a mechanism-to-metric map that connects trait tuning to PK readouts and PD/TI implications; (ii) a standardized, route-stratified table of ln-ratio effects with explicit vehicle/excipient flags; and (iii) a pragmatic decision framework to triage candidates (by logP/solubility and barrier goals) and design reproducible studies with safety checks (CARPA, anti-PEG/ABC, inorganic retention). Collectively, these elements advance anticipatory, model-informed nanoformulation design and provide quantitative anchors for future vehicle-matched, mechanism-driven comparisons.

22 April 2021 in Pharmaceutics
Verified
Journal Article
Open access
PDF file
CBCristina Díaz Barriga
Cristina Díaz Barriga
FVFrancisca Villanueva-Flores
Francisca Villanueva-Flores
KQKatrin Quester
Katrin Quester
AZAndrés Zárate-Romero
Andrés Zárate-Romero
RCRuben Cadena-Nava
Ruben Cadena-Nava
AHAlejandro Huerta-Saquero
Alejandro Huerta-Saquero
Asparaginase (ASNase) is a biopharmaceutical for Acute Lymphoblastic Leukemia (ALL) treatment. However, it shows undesirable side effects such as short lifetimes, susceptibility to proteases, and immunogenicity. Here, ASNase encapsidation was genetically directed in bacteriophage P22-based virus-like particles (VLPs) (ASNase-P22 nanoreactors) as a strategy to overcome these challenges. ASNase-P22 was composed of 58.4 ± 7.9% of coat protein and 41.6 ± 8.1% of tetrameric ASNase. Km and Kcat values of ASNase-P22 were 15- and 2-fold higher than those obtained for the free enzyme, respectively. Resulting Kcat/Km value was 2.19 × 105 M−1 s−1. ASNase-P22 showed an aggregation of 60% of the volume sample when incubated at 37 °C for 12 days. In comparison, commercial asparaginase was completely aggregated under the same conditions. ASNase-P22 was stable for up to 24 h at 37 °C, independent of the presence of human blood serum (HBS) or whether ASNase-P22 nanoreactors were uncoated or PEGylated. Finally, we found that ASNase-P22 caused cytotoxicity in the leukemic cell line MOLT-4 in a concentration dependent manner. To our knowledge, this is the first work where ASNase is encapsulated inside of VLPs, as a promising alternative to fight ALL.