Fluid absorption by skin tissue during intradermal injections through hollow microneedles

Abstract

Hollow microneedles are an emerging technology for delivering drugs and therapeutics, such as vaccines and insulin, into the skin. Although the benefits of intradermal drug delivery have been known for decades, our understanding of fluid absorption by skin tissue has been limited due to the difficulties in imaging a highly scattering biological material such as skin. Here, we report the first real-time imaging of skin tissue at the microscale during intradermal injections through hollow microneedles, using optical coherence tomography. We show that skin tissue behaves like a deformable porous medium and absorbs fluid by locally expanding rather than rupturing to form a single fluid filled cavity. We measure the strain distribution in a cross section of the tissue to quantify local tissue deformation, and find that the amount of volumetric expansion of the tissue corresponds closely to the volume of fluid injected. Mechanically restricting tissue expansion limits fluid absorption into the tissue. Our experimental findings can provide insights to optimize the delivery of drugs into skin for different therapeutic applications, and to better model fluid flow into biological tissue.

Clustering and erratic movement patterns of syringe-injected versus mosquito-inoculated malaria sporozoites underlie decreased infectivity

“…Importantly, our study demonstrates that state-of-the-art imaging (analysis) techniques can provide valuable quantitative assessments of parameters affecting sporozoite migration. Our ex vivo set-up combined with spinning-disk confocal microscopy and sporozoite tracking software enabled 1) the visualization of (the sporozoite distribution throughout) the whole inoculation and injection site (up to 100 mm 2 ), whereas up to now only one field of view (<0.5 mm 2 ) was visualized during in vivo live imaging (13,16,35), 2) the visualization of morphological tissue deformation as a result of pressure of fluid injection, previously acknowledged as an important parameter regarding transdermal drug delivery (36)(37)(38), but not yet visualized at a micron level resolution and 3) a multidimensional analysis of sporozoite motility unveiling an remarkable interplay between motility parameters which were up to now only studied independently (15)(16)(17). Further research is needed to study the role of other potential contributors not accounted for in this imaging study, such as their preprocessing (manual extraction from salivary glands in culture medium instead of saliva (14,39,40)).…”

Modelling Hydrocortisone Pharmacokinetics on a Subcutaneous Pulsatile Infusion Replacement Strategy in Patients with Adrenocortical Insufficiency

“…Then, if t = 1260 min (at 12:00 p.m.), = (see also Appendix E ). In relation to consideration (iii), we hypothesized that a small spherical pressure region is created within the subcutaneous tissue following the infusion of the HC solution [ 24 , 25 , 26 , 27 ].…”

Recent advances in microneedles-mediated transdermal delivery of protein and peptide drugs

“…Hollow MNs are sub-millimeter devices acted like micron-scale syringes, which can penetrate the stratum corneum to allow the flow of liquid formulation into the epidermis or dermis 59 . In the simplest form, drug delivery using hollow MNs is achieved through passive diffusion.…”

“…Most vaccines are administered by subcutaneous or intramuscular injection, which is relatively painful, resulting in poor patient compliance 104 . There are a large number of antigen presenting cell populations in the skin, such as macrophages, dermal dendritic cells (DCs), and Langerhans cells, making the skin a unique target for immunomodulation 59 , 105 , 106 , 107 . MNs are easy to use with minimal pain, which provide a promising platform for transcutaneous immunization with improved efficacy 108 , 109 , 110 ( Fig.…”