Patchless administration of canine influenza vaccine on dog's ear using insertion-responsive microneedles (IRMN) without removal of hair and its in vivo efficacy evaluation.

Microneedles provide the advantages of convenience and compliance by avoiding the pain and fear of needles that animals often experience. Insertion-responsive microneedles (IRMN) were used for administration to a hairy dog without removing the dog's hair. Canine H3N2 vaccine was administered with IRMN attached to the dog's ears ex vivo and the conventional microneedle system (MN) was administered for 15 min to compare puncture performance and delivery efficiency. The vaccine was also administered to compare antibody formation using IRMN with the use of intramuscular injection. The veterinarian observed the behavior of the dog during the course of the administration and compared the response to IRMN with that of intramuscular administration. The tips of IRMN were separated from the base and delivered into the hairy skin successfully. Puncture performance of IRMN were the same as that of coated microneedles (95%), but delivery efficiency of IRMN were 95% compared to less than 1% for coated microneedles. The H3N2 vaccine inoculated into the dog's ears showed the same antibody formation as the intramuscular injection. The dog appeared to be more comfortable with IRMN administration compared to syringe administration. IRMN are the first microneedle system to deliver a canine vaccine successfully into a hairy dog without removal of the dog's hair. The use of IRMN can provide both convenience and compliance for both the dog and the owner.

Insertion-responsive microneedles for rapid intradermal delivery of canine influenza vaccine.

In this study, we present transcutaneous influenza vaccination using a novel tip-separable microneedle system called insertion-responsive microneedles (IRMNs). IRMNs are composed of dissolvable hyaluronic acid (HA) tips and biocompatible polycaprolactone (PCL) bases, the tip of which is instantly separated from the base during microneedle insertion and retraction. Vaccine antigens derived from canine influenza virus (A/canine/VC378/2012; H3N2) were successfully coated on HA tips by rapidly freezing the tips prior to coating. An ex vivo porcine skin insertion test showed that IRMNs were capable of penetrating the skin without tip breakage and releasing the coated materials within the skin. The thermal stability of the vaccine as determined by hemagglutination assay revealed that the coated vaccine partially maintained its activity when stored at 50 °C for 3 weeks, whereas the liquid form completely lost the activity. Immunization in guinea pigs showed that hemagglutination inhibition (HI) antibodies induced by IRMNs were two times higher than those induced by intramuscular (IM) injections. When challenged with influenza A/canine/Korea/01/2007 (H3N2) wild-type virus 2 weeks after the second vaccination, viral shedding was completely eliminated at 8 days post infection in both IRMNs and IM injection groups. Our results suggest that IRMNs have great potential for rapid and convenient vaccination, which will be particularly attractive for animal vaccinations.

Immediate separation of microneedle tips from base array during skin insertion for instantaneous drug delivery.

We have developed an insertion-responsive microneedle (IRMN) system that enables prompt drug delivery through the skin without attaching a skin patch. This system consists of square pyramidal hyaluronic acid (HA) microneedle tips and polycaprolactone (PCL) base arrays. During skin insertion, HA tips can be immediately separated from PCL base arrays due to the relatively weak adhesion strength between HA and PCL. Two base designs using truncated square pyramid stands, one without a wall (no-walled stand, NWS) and another with a wall on one side of the stand (single-walled stand, SWS), were prepared to study the effect of base geometry on the mechanical behavior of IRMNs. Ex vivo skin insertion tests showed successful separation of the tips from the base array upon insertion, regardless of the presence of a wall on the stand. However, only IRMNs-SWS were deeply embedded within the skin. Mechanical testing results demonstrated that the presence of a wall on the base enhanced the mechanical stability of the IRMNs. The wall also provided adequate adhesion between the tips and base, preventing the tips from breaking during insertion, while allowing the needle tip to separate upon removal. Histological examination confirmed that the tips were successfully separated from the base, embedded in the skin, and released fluorescent dyes within the skin. Our results suggest that the IRMN system is promising for the rapid and accurate delivery of various molecules through the skin, while improving user convenience by eliminating the need to attach microneedles to the skin.

The Impact of Lumbosacral Transitional Vertebrae on Therapeutic Outcomes of Transforaminal Epidural Injection in Patients with Lumbar Disc Herniation.

BACKGROUND: Although some studies have evaluated the clinical impact of lumbosacral transitional vertebrae (LSTV), few have attempted to determine an effective conservative treatment method for lumbar disc herniation (LDH) presenting concurrently with LSTV. METHODS: We prospectively enrolled 291 consecutive patients who were followed-up for at least one year after transforaminal epidural injection (TFEI) for LDH. We confirmed the presence of LSTV with Paik et al.'s method, the Castellvi classification, and the Southworth and Bersack method. Clinical outcomes were evaluated with a visual analogue scale (VAS) for pain intensity and the Oswestry Disability Index (ODI) for functional status. RESULTS: Of the 291 patients, 47 (16.2%) had LSTV, including 33 with sacralization and 14 with lumbarization, while 244 (83.8%) did not have LSTV. Patients in both groups improved significantly after TFEI in terms of the VAS (P < 0.001) and ODI (P < 0.001) scores. However, LDH patients with LSTV had a worse clinical outcome after six months of TFEI than did those without LSTV, with a significant difference between groups for both the VAS (P < 0.01) and ODI (P = 0.01) scores. LDH patients with sacralization had worse post-treatment clinical outcomes than LDH patients with lumbarization (P < 0.001) or LDH patients without LSTV (P < 0.001). CONCLUSIONS: Sacralization can reduce the improvement after TFEI among LDH patients, while lumbarization appears to have no direct effect on TFEI outcomes. The presence of sacralization should be identified before TFEI, and if present, patients should be informed that the outcomes of TFEI may not be as good as they would be if sacralization was not present.