Targeting the Skin for Microneedle Delivery of Influenza Vaccine

Koutsonanos, Dimitrios G.; Compans, Richard W.; Skountzou, Ioanna

doi:10.1007/978-1-4614-6217-0_13

Cited by 36 publications

(31 citation statements)

References 132 publications

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“…However, migration of cells can occur, initiated by the release of molecules, such as cytokines and chemokines, from skin cells (Ueno et al 2007;Koutsonanos et al 2013). These molecules provide a signal to cells from both inside and outside the skin to migrate towards the location of secretion (Del Pilar Martin et al 2012;Koutsonanos et al 2013) and thereby repopulating the skin and changing the number and distribution of cells within the skin. In addition, these signaling molecules can influence the maturation and migration of antigen presenting cells towards the lymph nodes (Koutsonanos et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…These molecules provide a signal to cells from both inside and outside the skin to migrate towards the location of secretion (Del Pilar Martin et al 2012;Koutsonanos et al 2013) and thereby repopulating the skin and changing the number and distribution of cells within the skin. In addition, these signaling molecules can influence the maturation and migration of antigen presenting cells towards the lymph nodes (Koutsonanos et al 2013). If these processes were included in the model, the release rate may prove to influence the evoked immune response when a sustained period is simulated, since it has been reported that a vaccination regime over many days can increase the response (Johansen et al 2008).…”

Section: Discussionmentioning

confidence: 99%

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Predicting the optimal geometry of microneedles and their array for dermal vaccination using a computational model

Römgens

Bader

Bouwstra

et al. 2016

Computer Methods in Biomechanics and Biomedical Engineering

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a a soft tissue Biomechanics and engineering, department of Biomedical engineering, eindhoven university of technology, eindhoven, the netherlands; b Faculty of health sciences, university of southampton, southampton, uK; c division of drug delivery technology, leiden academic Centre for drug research, leiden university, leiden, the netherlands ABSTRACT Microneedle arrays have been developed to deliver a range of biomolecules including vaccines into the skin. These microneedles have been designed with a wide range of geometries and arrangements within an array. However, little is known about the effect of the geometry on the potency of the induced immune response. The aim of this study was to develop a computational model to predict the optimal design of the microneedles and their arrangement within an array. The three-dimensional finite element model described the diffusion and kinetics in the skin following antigen delivery with a microneedle array. The results revealed an optimum distance between microneedles based on the number of activated antigen presenting cells, which was assumed to be related to the induced immune response. This optimum depends on the delivered dose. In addition, the microneedle length affects the number of cells that will be involved in either the epidermis or dermis. By contrast, the radius at the base of the microneedle and release rate only minimally influenced the number of cells that were activated. The model revealed the importance of various geometric parameters to enhance the induced immune response. The model can be developed further to determine the optimal design of an array by adjusting its various parameters to a specific situation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Predicting the optimal geometry of microneedles and their array for dermal vaccination using a computational model

Römgens

Bader

Bouwstra

et al. 2016

Computer Methods in Biomechanics and Biomedical Engineering

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“…One such example for vaccines delivery is reported by Edmonston-Zagreb for measles vaccination (Nordquist et al, 2007;Herwadkar & Banga, 2012;Kis et al, 2012;Singh et al, 2012;Edens et al, 2013;Koutsonanos et al, 2013;Ling & Chen, 2013;Cai et al, 2014;Gill et al, 2014). Vaccinations have the capacity to be delivered using MN patches, which require the patient to have no specialized training or the need for cold/refrigerated storage; this in turn can reduce the spread of diseases Edens et al, 2013).…”

Section: Why Mns?mentioning

confidence: 99%

Microneedles for drug delivery: trends and progress

2014

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In recent years, there has been a surge in the research and development of microneedles (MNs), a transdermal delivery system that combines the technology of transdermal patches and hypodermic needles. The needles are in the hundreds of micron length range and therefore allow relatively little or no pain. For example, biodegradable MNs have been researched in the literature and have several advantages compared with solid or hollow MNs, as they produce non-sharp waste and can be designed to allow rapid or slow release of drugs. However, they also pose a disadvantage as successful insertion into the stratum corneum layer of the skin relies on sufficient mechanical strength of the biodegradable material. This review looks at the various technologies developed in MN research and shows the rapidly growing numbers of research papers and patent publications since the first invention of MNs (using time series statistical analysis). This provides the research and industry communities a valuable synopsis of the trends and progress being made in this field.

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“…When an antigen is delivered in the epidermis and dermis, it will diffuse through the different skin layers (Raphael et al, 2013;Römgens et al, 2015). One of these layers, the viable epidermis, is mainly composed of keratinocytes, but also contains a large population of Langerhans cells (Koutsonanos et al, 2013). Beneath the epidermis lies the dermis, a relatively thick layer rich in collagen fibres.…”

Section: Introductionmentioning

confidence: 99%

“…They can be recognized, bind and be internalized by the cells residing in the skin (Giese, 2013;Koutsonanos et al, 2013). This uptake of antigens occurs by receptor-mediated endocytosis or by fluid phase pinocytosis (Abbas et al, 2012;Mizuno et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

A theoretical compartment model for antigen kinetics in the skin

Römgens

Bader

Bouwstra

et al. 2016

European Journal of Pharmaceutical Sciences

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The skin is a promising location for vaccination with its abundant population of antigen capturing and presenting cells. The development of new techniques, such as the use of microneedles, can facilitate the delivery of vaccines into the skin. In recent years, many different types of microneedle arrays have been designed. However, their geometry and arrangement within an array may be optimized to trigger sufficient antigen presenting cells. A computational model can support the rational design of microneedle arrays. Therefore, the aim of the current study was to describe the distribution and kinetics of a delivered antigen within the skin using a theoretical compartment model, which included binding of antigens to receptors and their uptake by cells, and to determine which parameters should be measured to validate the model for a specific application. Multiple simulations were performed using a high and low antigen delivery dose and a range of values for the rate constants. The results indicated that the cells were highly saturated when a high dose was applied, while for a low dose saturation was only reached in 5% of the simulations. This was caused by the difference in the ratio between the administered dose and the available binding sites and suggests the dose should be adapted to the number of cells and receptors for a specific compound. The sensitivity analysis of the model parameters confirmed that the initial dose and receptor concentrations were indeed the two parameters that had the largest influence on the variance in antigen concentrations within the cells and circulation at equilibrium. Hence, these parameters are important to be measured in vivo. The presented pharmacokinetics model can be used in future computational models to predict the influence of microneedle array geometry to optimize their design.

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Targeting the Skin for Microneedle Delivery of Influenza Vaccine

Cited by 36 publications

References 132 publications

Predicting the optimal geometry of microneedles and their array for dermal vaccination using a computational model

Predicting the optimal geometry of microneedles and their array for dermal vaccination using a computational model

Microneedles for drug delivery: trends and progress

A theoretical compartment model for antigen kinetics in the skin

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