Development and psychometric testing of the Heart-Healthy Information Questionnaire.

AIMS: This study aimed to develop a reliable and valid scale, i.e. the Heart-Healthy Information Questionnaire (HHIQ). METHODS AND RESULTS: The HHIQ was developed in three phases: (i) creating the item pool, (ii) conducting a preliminary evaluating the items, and (iii) refining the scale and evaluating psychometric properties. An initial item pool of 77 items with a 3-point True/False format with a 'Don't know' option was extracted from the literature review and 54 items reached content validity. The psychometric properties of HHIQ were tested with 1315 individuals without cardiovascular disease. By using the exclusion criteria of the difficulty index (>0.95), discrimination index (<10.0), and item-total correlation (tetrachoric coefficient <0.2), 50 items were finally selected. The construct validity was determined by using the known-groups validation: Individuals (n = 107) who were educated with heart-healthy education sessions showed significantly higher scores of the HHIQ than those (n = 107) who were not educated (P = 0.015). The Kuder-Richardson formula 20 coefficient indicated good internal consistency (0.85), and the test-retest reliability coefficient with a 15-day interval also indicated good stability (0.78). A total score of the HHIQ was significantly correlated with a total score of the Evaluation Tool for Metabolic Syndrome Modification Lifestyles (ρ = 0.23, P < 0.001). CONCLUSION: The HHIQ showed good psychometric properties of validity and reliability and may be useful to evaluate the knowledge levels of heart-healthy information in the areas of cardiovascular disease prevention.

Development of the H3N2 influenza microneedle vaccine for cross-protection against antigenic variants.

Due to the continuously mutating nature of the H3N2 virus, two aspects were considered when preparing the H3N2 microneedle vaccines: (1) rapid preparation and (2) cross-protection against multiple antigenic variants. Previous methods of measuring hemagglutinin (HA) content required the standard antibody, thus rapid preparation of H3N2 microneedle vaccines targeting the mutant H3N2 was delayed as a result of lacking a standard antibody. In this study, H3N2 microneedle vaccines were prepared by high performance liquid chromatography (HPLC) without the use of an antibody, and the cross-protection of the vaccines against several antigenic variants was observed. The HA content measured by HPLC was compared with that measured by ELISA to observe the accuracy of the HPLC analysis of HA content. The cross-protection afforded by the H3N2 microneedle vaccines was evaluated against several antigenic variants in mice. Microneedle vaccines for the 2019-20 seasonal H3N2 influenza virus (19-20 A/KS/17) were prepared using a dip-coating process. The cross-protection of 19-20 A/KS/17 H3N2 microneedle vaccines against the 2015-16 seasonal H3N2 influenza virus in mice was investigated by monitoring body weight changes and survival rate. The neutralizing antibody against several H3N2 antigenic variants was evaluated using the plaque reduction neutralization test (PRNT). HA content in the solid microneedle vaccine formulation with trehalose post-exposure at 40℃ for 24 h was 48% and 43% from the initial HA content by HPLC and ELISA, respectively. The vaccine was administered to two groups of mice, one by microneedles and the other by intramuscular injection (IM). In vivo efficacies in the two groups were found to be similar, and cross-protection efficacy was also similar in both groups. HPLC exhibited good diagnostic performance with H3N2 microneedle vaccines and good agreement with ELISA. The H3N2 microneedle vaccines elicited a cross-protective immune response against the H3N2 antigenic variants. Here, we propose the use of HPLC for a more rapid approach in preparing H3N2 microneedle vaccines targeting H3N2 virus variants.

Ovalbumin and cholera toxin delivery to buccal mucus for immunization using microneedles and comparison of immunological response to transmucosal delivery.

The oral mucosa is an effective site for vaccination. However, for oral mucosal vaccines, delivery of the right dose of vaccine is not possible due to the water-rich environment. In this study, the buccal mucosa, which is easy to access using a microneedle array in the oral cavity, was selected as the administration site. The immune responses to the use of microneedles to conventional transmucosal delivery were compared. In addition, the adjuvant effect of the addition of cholera toxin (CT) to the drug formulation was observed. Two kinds of patches were prepared: (1) Ovalbumin (OVA) was dip coated only on the tips of microneedles (C-OVA-MN) and (2) OVA was coated on the surface of a flat disk patch substrate without microneedles (C-OVA-D). The drug delivery properties of C-OVA-MN and C-OVA-D were investigated using fluorescent-labeled OVA (OVA/FITC). Each patch was administered to mice twice, 2 weeks apart, and then antibody titers were measured. A microneedle patch can deliver vaccine into the epithelium of the buccal mucosa in a short period of time compared to transmucosal delivery. A microneedle system of C-OVA-MN showed a high serum IgG titer. In addition, CT triggered CD8+ and CD4+ T cell-mediated immune responses. Through this study, we present the possibility of a new method of vaccination to the buccal mucosa using microneedles and CT adjuvant. Illustration of delivery of vaccine to the oral mucosal epithelium using a microneedle patch: Ovalbumin (OVA)-coated microneedle (C-OVA-MN) consists of tip, step, and coating formulation. Microneedle patch coated with OVA formulation is targeting buccal mucosa, which is easy to access in the oral cavity. OVA is delivered to the buccal epithelium precisely using a microneedle patch, and OVA is delivered by transmucosal route using a disk patch.

Progress in microneedle array patch (MAP) for vaccine delivery.

A microneedle array patch (MAP) has been developed as a new delivery system for vaccines. Preclinical and clinical trials with a vaccine MAP showed improved stability, safety, and immunological efficacy compared to conventional vaccine administration. Various vaccines can be delivered with a MAP. Currently, microneedle manufacturers can mass-produce pharmaceutical MAP and cosmetic MAP and this mass-production system can be adapted to produce a vaccine MAP. Clinical trials with a vaccine MAP have shown comparable efficacy with conventional administration, and discussions about regulations for a vaccine MAP are underway. However, there are concerns of reasonable cost, mass production, efficacy, and safety standards that meet FDA approval, as well as the need for feedback regarding the best method of administration. Currently, microneedles have been studied for the delivery of many kinds of vaccines, and preclinical and clinical studies of vaccine microneedles are in progress. For the foreseeable future, some vaccines will continue to be administered with syringes and needles while the use of a vaccine MAP continues to be improved because of the advantages of less pain, self-administration, improved stability, convenience, and safety.

Microneedle Array Patch (MAP) Consisting of Crosslinked Hyaluronic Acid Nanoparticles for Processability and Sustained Release.

AIMS: Crosslinked hyaluronic acid (X-linked HA) is not suitable for making microneedles because of the low fluidity of X-linked HA hydrogel. Microneedles were fabricated using X-linked HA nanoparticles (X-linked HA-NPs) to utilize the sustained drug delivery capability of X-linked HA-NPs and to obtain the processability advantages of X-linked HA. METHOD: The puncture performance of a microneedle array patch (MAP) made of crosslinked hyaluronic acid nanoparticles (X-linked HA-NP-MAP) was evaluated by insertion in vitro into porcine skin. After a predetermined attachment time, the remaining height of the X-linked HA-NP-MAP was measured to determine the dissolution rate. X-linked HA-NP-MAP and free HA-MAP containing Rhodamine B isothiocyanate-dextran were administered into the back skin of mice, and the relative fluorescent intensity in the back skin was measured over time. RESULTS: The puncture performance of the X-linked HA-NP-MAP was over 90%. The diameter of redispersed X-linked HA-NPs was same as that of the premolded X-linked HA-NPs. The dissolution rate was not different from that of free HA-MAP. In an in vivo experiment, X-linked HA-NP-MAP was administered into the mouse's back skin successfully and the relative fluorescent intensity of X-linked HA-NP-MAP lasted longer than that of HA-MAP. CONCLUSION: X-linked HA-NPs provide the biocompatibility, the processability of micromolding, sustained drug release, successful penetration into the skin, and relatively short insertion time for full disintegration of NPs in the skin. X-linked HA-NP-MAP can be used for various applications that require several days of sustained drug release.