Molecular distribution in intradermal injection for transfer and delivery of therapeutics

Abstract

Intradermal (ID) injection is a technique widely used in laboratorial and clinical applications. The boundary of the dome-like bleb formed during injection is assumed to represent the lateral extent of the injected material. This work systematically characterizes cargo molecule distribution (puddle) as a function of injection volume and molecular/particle size in rat skin post ID injection. In general, results indicate that the puddle forms a subdomain laterally contained within the bleb, with an area inversely correlating to the molecular size of the injected material. For 50 μL and 100 µL injections, the average area of the bleb was 40.97 ± 6.30 mm2 and 55.64 ± 8.20 mm2, respectively, regardless of the molecular/particle size. On the other hand, the area of the puddle was dependent on the molecular size and ranged between 45.38 ± 8.29 mm2 and 6.14 ± 4.50 mm2 for 50 µL injections, and 66.64 ± 11.22 mm2 and 11.50 ± 9.67 mm2 for 100 µL injections. The lateral distribution appears to have no time-dependency up to 10 min post injection. The trend in the depth of cargo penetration is also similar, with smaller particles extending deeper into the dermis and subcutaneous fat layers. Because the area of puddle can be significantly less than that of the bleb, establishing base characterization is essential to understand cellular interactions with the injected biological substances.

Preclinical evaluation of performance, safety and usability of VAX-ID®, a novel intradermal injection device

“…Thus, bleb formation, although it is a visual sign of successful ID injection, might not be the best indicator for the success of injection due to the different variables that affect the bleb formation, shape, and diameter. This is also in line with the findings of Lallow et al [34] who also demonstrated that the puddle (distribution of the liquid in the skin) is more important than the shape and formation of the bleb.…”

Tissue Tension and Strain as Indicators of Suction-mediated Cutaneous DNA Transfection: A Parametric Study

“…This result is consistent with previous observations demonstrating that DNA cargo typically remains within the bleb area. [41] Spatial expression pattern is correlated to strain pattern Results of the numerical simulations demonstrate a correlation between the tissue strain and GFP expression patterns. Figure 3C shows three-dimensional images of COMSOL simulation of negative-pressure application on the tissue model surface.…”

“…These results allude to important considerations in using suction as a means of enhancing expression following primary ID injection. Our prior study [41] revealed that cargo for ID injection was contained within the visible bleb, especially for macromolecules such as DNA. Therefore, although in general tissue strain does scale with nozzle size for the same suction pressure, larger nozzles have limited benefits as they enclose areas greater than the bleb (see Fig.…”

“…In a follow-up work, we have examined the spatial distribution for variable-sized cargoes (dextran, nanoparticles, and DNA) within an intradermal injection, which is an important aspect for secondary delivery mechanisms as their action sites need to co-localize with the cargo. [41]…”

Bacterial-host adhesion dominated by collagen subtypes remodeled by osmotic pressures

“…Also, it was demonstrated that S. aureus mutants lacking FnBPB or ClfB had a reduced ability to adhere to the skin of patients with atopic dermatitis (AD) 35 . So far, one of the major challenges in traditional bacterium-directed chemotherapies lies in the crisis of antibiotic resistance, which has led to increasing interest in designing antibacterial strategies associated with host microenvironments to enhance antibiotic efficacies [36][37][38][39] . As a matter of fact, it has been reported that biomechanical microenvironments around host cells can exert a crucial impact on bacterial-cell interactions such as binding of adhesins to host cell receptors 40 and bacterial infection of epithelial cells and intracellular accumulation of antibiotics 41 .…”