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Mara Leone

Bio: Mara Leone is an academic researcher from Leiden University. The author has contributed to research in topics: Cationic liposome & Adjuvant. The author has an hindex of 7, co-authored 8 publications receiving 228 citations.

Papers
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Journal ArticleDOI
TL;DR: This review focuses on dissolving microneedles that after penetration into the skin dissolve releasing the encapsulated antigen, and the immunogenicity of antigens formulated in dissolvingmicroneedle are addressed.
Abstract: The dermal route is an attractive route for vaccine delivery due to the easy skin accessibility and a dense network of immune cells in the skin. The development of microneedles is crucial to take advantage of the skin immunization and simultaneously to overcome problems related to vaccination by conventional needles (e.g. pain, needle-stick injuries or needle re-use). This review focuses on dissolving microneedles that after penetration into the skin dissolve releasing the encapsulated antigen. The microneedle patch fabrication techniques and their challenges are discussed as well as the microneedle characterization methods and antigen stability aspects. The immunogenicity of antigens formulated in dissolving microneedles are addressed. Finally, the early clinical development is discussed.

131 citations

Journal ArticleDOI
TL;DR: Several critical formulation parameters are identified for the further development of NP‐loaded dissolving MNs loaded with PLGA nanoparticles co‐encapsulating ovalbumin (OVA) and poly(I:C) for intradermal immunisation.

59 citations

Journal ArticleDOI
TL;DR: Results suggest that the polydimethylsiloxane mold design has an impact on the manufacturing ofdMNs, the increase in antigen loading in dMNs affects the microneedle dissolution and d MNs are a valid alternative for vaccine administration over conventional injection.

37 citations

Journal ArticleDOI
TL;DR: Data demonstrate that an applicator is an important tool to determine optimal application conditions with ex vivo human skin, and microneedles pierced the skin more efficiently when applied by impact application as compared to application via pressing force.
Abstract: Microneedle technologies have been developed for dermal drug and vaccine delivery, including hollow-, solid-, coated-, and dissolving microneedles. Microneedles have been made in many different geometries and of many different materials, all of which may influence their skin-penetrating ability. To ensure reproducible and effective drug and vaccine delivery via microneedles, the optimal insertion parameters should be known. Therefore, a digitally-controlled microneedle applicator was developed to insert microneedles into the skin via impact insertion (velocity) or via pressing force insertion. Six microneedle arrays with different geometries and/or materials were applied onto ex vivo human skin with varying velocities or pressing forces. Penetration efficiency and delivered antigen dose into the skin after application of microneedles were determined. In general, microneedles pierced the skin more efficiently when applied by impact application as compared to application via pressing force. However, the angle of application of the applicator on the skin can affect the velocity of the impact, influencing the penetration efficiency of microneedles. Regarding the antigen delivery into the skin, the delivered dose was increasing by increasing the velocity or pressure, and thus, increasing the penetration efficiency. These data demonstrate that an applicator is an important tool to determine optimal application conditions with ex vivo human skin.

28 citations

Journal ArticleDOI
TL;DR: The aim of this study was to investigate the effect of the molecular weight of hyaluronan, a polymer widely used in the fabrication of dMNs, on the dissolution of microneedles in the skin in time as well as the antibody response in mice and T-cell activation in vitro.

26 citations


Cited by
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Journal ArticleDOI
TL;DR: The use of poloxamers as biosurfactants is evaluated since they are able to form micelles in an aqueous environment above a concentration threshold known as critical micelle concentration (CMC), which is exploited for drug delivery and different therapeutic applications.
Abstract: This review article focuses on thermoresponsive hydrogels consisting of poloxamers which are of high interest for biomedical application especially in drug delivery for ophthalmic, injectable, transdermal, and vaginal administration. These hydrogels remain fluid at room temperature but become more viscous gel once they are exposed to body temperature. In this way, the gelling system remains at the topical level for a long time and the drug release is controlled and prolonged. Poloxamers are synthetic triblock copolymers of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO), also commercially known as Pluronics®, Synperonics® or Lutrol®. The different poloxamers cover a range of liquids, pastes, and solids, with molecular weights and ethylene oxide–propylene oxide weight ratios varying from 1100 to 14,000 and 1:9 to 8:2, respectively. Concentrated aqueous solutions of poloxamers form thermoreversible gels. In recent years this type of gel has arouse interest for tissue engineering. Finally, the use of poloxamers as biosurfactants is evaluated since they are able to form micelles in an aqueous environment above a concentration threshold known as critical micelle concentration (CMC). This property is exploited for drug delivery and different therapeutic applications.

181 citations

Journal ArticleDOI
TL;DR: Different transdermal insulin delivery techniques and their respective advantages and limitations are focused on, including chemical enhancers-promoted, electrically enhanced, mechanical force-triggered, and microneedle-assisted methods.

180 citations

Journal ArticleDOI
TL;DR: This overview on skin delivery considers the evolution of the principles of percutaneous ab-sorption and skin products from ancient times to today and the development of technologies to effectively and quantitatively deliver solutes across this barrier to specific target sites in the skin and beyond.
Abstract: This overview on skin delivery considers the evolution of the principles of percutaneous absorption and skin products from ancient times to today. Over the ages, it has been recognised that products may be applied to the skin for either local or systemic effects. As our understanding of the anatomy and physiology of the skin has improved, this has facilitated the development of technologies to effectively and quantitatively deliver solutes across this barrier to specific target sites in the skin and beyond. We focus on these technologies and their role in skin delivery today and in the future.

159 citations

Journal ArticleDOI
TL;DR: In this article, the current state of knowledge on immune cell functions during skin tissue regeneration is first discussed, and then advanced technologies used to design immunomodulatory hydrogels for controlling macrophages' polarization are summarized.
Abstract: With all the advances in tissue engineering for construction of fully functional skin tissue, complete regeneration of chronic wounds is still challenging. Since immune reaction to the tissue damage is critical in regulating both the quality and duration of chronic wound healing cascade, strategies to modulate the immune system are of importance. Generally, in response to an injury, macrophages switch from pro-inflammatory to an anti-inflammatory phenotype. Therefore, controlling macrophages' polarization has become an appealing approach in regenerative medicine. Recently, hydrogels-based constructs, incorporated with various cellular and molecular signals, have been developed and utilized to adjust immune cell functions in various stages of wound healing. Here, the current state of knowledge on immune cell functions during skin tissue regeneration is first discussed. Recent advanced technologies used to design immunomodulatory hydrogels for controlling macrophages' polarization are then summarized. Rational design of hydrogels for providing controlled immune stimulation via hydrogel chemistry and surface modification, as well as incorporation of cell and molecules, are also dicussed. In addition, the effects of hydrogels' properties on immunogenic features and the wound healing process are summarized. Finally, future directions and upcoming research strategies to control immune responses during chronic wound healing are highlighted.

155 citations

Journal ArticleDOI
TL;DR: Graphical abstract Polymer microneedle promotes the delivery of chemical and biological drugs through the skin through its role in cell reprograming and wound healing.

137 citations