Flavia Fontana

University of Helsinki

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Hélder A. Santos

University of Helsinki

Jouni Hirvonen

University of Helsinki

Alexandra Correia

University of Helsinki

Ermei Mäkilä

University of Turku

Jarno Salonen

University of Turku

Dongfei Liu

Tsinghua University

Mohammad‐Ali Shahbazi

University Medical Center Groningen

Hongbo Zhang

Åbo Akademi University

Patrícia Figueiredo

University of Helsinki

Giulia Torrieri

University of Helsinki

Cooperative Institutions

University of Helsinki

University of Groningen

University of Turku

Shanghai Jiao Tong University

Harvard University

University of Naples Federico II

University Medical Center Groningen

Pharmaceutical Biotechnology (Czechia)

Chinese Academy of Sciences

University of Chinese Academy of Sciences

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Double‐Layered Polyvinylpyrrolidone–Poly(methyl vinyl ether‐alt‐maleic acid)‐Based Microneedles to Deliver Meloxicam: An In Vitro, In Vivo, and Short‐Term Stability Evaluation Study

Advanced Therapeutics (2023)

Carmine D’Amico Flavia Fontana Nesma El‐Sayed Khalil Elbadri Alexandra Correia

Abstract This study aims to explore the use of polymeric microneedles (MNs) for the transdermal delivery of drugs, a noninvasive and convenient method that avoids first‐pass metabolism and gastrointestinal complications. Specifically, a double‐layered MN formulation is developed using polyvinylpyrrolidone and cross‐linked poly(methyl vinyl ether‐ alt ‐maleic acid), comprising a dissolvable layer and a hydrogel‐forming layer. Meloxicam serves as the model drug, and no organic solvents are employed in the manufacturing process to reduce toxicity. Coherent anti‐Stokes Raman spectroscopy (CARS) is utilized to confirm that the manufacturing process does not alter the drug's physical properties. In vitro and ex vivo studies demonstrate that the double‐layered MN formulation exhibits faster drug release in the first few hours, followed by a slower release. This results in extended bioavailability in vivo compared to the commercial oral formulation of meloxicam. Preliminary results indicate that the MN formulation is also effective in pain relief and inflammation reduction. The short‐term stability of the MN formulation is also confirmed, including its mechanical properties, sustained skin permeability, drug physical properties and distribution within MNs using CARS microscopy. Overall, these results suggest that the double‐layered MN formulation holds significant potential for transdermal drug delivery, offering a safer and more effective alternative to traditional oral administration.

Meloxicam

Polyvinylpyrrolidone

Ex vivo

10.1002/adtp.202300138

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Citations (7)

Microfluidics as a cutting-edge technique for drug delivery applications

Journal of Drug Delivery Science and Technology (2016)

Flavia Fontana Mónica P. A. Ferreira Alexandra Correia Jouni Hirvonen Hélder A. Santos

Polymersome

Biopharmaceutical

10.1016/j.jddst.2016.01.010

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Citations (86)

Nanoparticles-based phototherapy systems for cancer treatment: Current status and clinical potential

Bioactive Materials (2022)

Jiachen Li Shiqi Wang Flavia Fontana Christos Tapeinos Mohammad‐Ali Shahbazi

Remarkable progress in phototherapy has been made in recent decades, due to its non-invasiveness and instant therapeutic efficacy. In addition, with the rapid development of nanoscience and nanotechnology, phototherapy systems based on nanoparticles or nanocomposites also evolved as an emerging hotspot in nanomedicine research, especially in cancer. In this review, first we briefly introduce the history of phototherapy, and the mechanisms of phototherapy in cancer treatment. Then, we summarize the representative development over the past three to five years in nanoparticle-based phototherapy and highlight the design of the innovative nanoparticles thereof. Finally, we discuss the feasibility and the potential of the nanoparticle-based phototherapy systems in clinical anticancer therapeutic applications, aiming to predict future research directions in this field. Our review is a tutorial work, aiming at providing useful insights to researchers in the field of nanotechnology, nanoscience and cancer.

Cancer Treatment

Cancer Therapy

Clinical Practice

10.1016/j.bioactmat.2022.11.013

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Citations (58)

Development of Innovative Multistage Nanovectors for Cancer Immunotherapy

Flavia Fontana Mohammad‐Ali Shahbazi Dongfei Liu Hongbo Zhang Ermei Mäkilä

Cancer Immunotherapy

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Biohybrid Nanovaccines in Murine Melanoma: Efficacy and Synergistic Combo Therapy with Immune Checkpoint Inhibitor

Flavia Fontana Cristian Capasso Manlio Fusciello Sara Feola Ermei Mäkilä

Immune checkpoint

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Biohybrid Vaccines for Improved Treatment of Aggressive Melanoma with Checkpoint Inhibitor

ACS Nano (2019)

Flavia Fontana Manlio Fusciello Christianne Groeneveldt Cristian Capasso Jacopo Chiaro

Recent approaches in the treatment of cancer focus on involving the immune system to control the tumor growth. The administration of immunotherapies, like checkpoint inhibitors, has shown impressive results in the long term survival of patients. Cancer vaccines are being investigated as further tools to prime tumor-specific immunity. Biomaterials show potential as adjuvants in the formulation of vaccines, and biomimetic elements derived from the membrane of tumor cells may widen the range of antigens contained in the vaccine. Here, we show how mice presenting an aggressive melanoma tumor model treated twice with the complete nanovaccine formulation showed control on the tumor progression, while in a less aggressive model, the animals showed remission and control on the tumor progression, with a modification in the immunological profile of the tumor microenvironment. We also prove that co-administration of the nanovaccine together with a checkpoint inhibitor increases the efficacy of the treatment (87.5% of the animals responding, with 2 remissions) compared to the checkpoint inhibitor alone in the B16.OVA model. Our platform thereby shows potential applications as a cancer nanovaccine in combination with the standard clinical care treatment for melanoma cancers.

Immune checkpoint

Cancer Immunotherapy

Tumor progression

10.1021/acsnano.8b09613

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Citations (42)

Peptide-guided resiquimod-loaded lignin nanoparticles convert tumor-associated macrophages from M2 to M1 phenotype for enhanced chemotherapy

Acta Biomaterialia (2020)

Patrícia Figueiredo Anni Lepland Pablo Scodeller Flavia Fontana Giulia Torrieri

10.1016/j.actbio.2020.09.038

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Citations (104)

Development of Biohybrid Multistage Nanovaccines for Melanoma

Flavia Fontana Cristian Capasso Mohammad‐Ali Shahbazi Dongfei Liu Manlio Fusciello

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Multifunctional Biomimetic Nanovaccines Based on Photothermal and Weak‐Immunostimulatory Nanoparticulate Cores for the Immunotherapy of Solid Tumors (Adv. Mater. 9/2022)

Advanced Materials (2022)

Jiachen Li Di Huang Ruoyu Cheng Patrícia Figueiredo Flavia Fontana

Nanovaccines A cancer cell membrane@porous silicon nanoparticles@Au nanovaccine is developed by Zhenyang Luo, Hélder A. Santos, Bing Xia, and co-workers in article number 2108012, based on weak-immunostimulatory porous silicon@Au nanoparticulate cores and multi-antigenic cancer cell membranes. These exogenous nanovaccines boost antitumor immunity, preventing the occurrence of solid tumors, and significantly inhibiting the growth and metastasis of solid tumors after photothermal therapy combined with immune checkpoint inhibitors.

Porous Silicon

Cancer Immunotherapy

10.1002/adma.202270074

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Microfluidics for Production of Particles: Mechanism, Methodology, and Applications

Small (2019)

Zehua Liu Flavia Fontana André Python Jouni Hirvonen Hélder A. Santos

Abstract In the past two decades, microfluidics‐based particle production is widely applied for multiple biological usages. Compared to conventional bulk methods, microfluidic‐assisted particle production shows significant advantages, such as narrower particle size distribution, higher reproducibility, improved encapsulation efficiency, and enhanced scaling‐up potency. Herein, an overview of the recent progress of the microfluidics technology for nano‐, microparticles or droplet fabrication, and their biological applications is provided. For both nano‐, microparticles/droplets, the previously established mechanisms behind particle production via microfluidics and some typical examples during the past five years are discussed. The emerging interdisciplinary technologies based on microfluidics that have produced microparticles or droplets for cellular analysis and artificial cells fabrication are summarized. The potential drawbacks and future perspectives are also briefly discussed.

10.1002/smll.201904673

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Citations (110)