Jian-Yang Gu

To overcome the limitations of repeated GH injection therapy, gelatin methacryloyl (GelMA)/hyaluronic acid (HA) composite hydrogel microneedles were fabricated for potential non-invasive transdermal delivery of recombinant human growth hormone (rhGH) and long-acting human growth hormone Fc fusion protein (hGH-Fc). All-atom molecular dynamics simulations combined with morphological, mechanical, and scanning electron microscopy (SEM) characterization were applied to screen optimal microneedle formulations, with Fourier transform infrared spectroscopy (FTIR) analysis and Parafilm M penetration tests verifying physicochemical compatibility and insertion capability. MD simulations revealed that rhGH stabilized the matrix via hydrogen bonds and electrostatic interactions, while hGH-Fc bound mainly through van der Waals forces. Through orthogonal screening of GelMA (5%, 10%, 15%) and HA (0.5%, 1%, 2%, 5%), the 10% GelMA with 0.5–2% HA was identified as the optimal range; the representative 10% GelMA/1% HA formulation exhibited a single-tip force exceeding 1.40 N and ~500 μm penetration in Parafilm M. This study offers a theoretical and technical basis for the design and optimization of hydrogel microneedle carriers for short- and long-acting GH delivery.

Background/Objectives: Given the overlapping seasonality of influenza (Flu) and respiratory syncytial virus (RSV) infections in human populations, Flu–RSV combination vaccines are urgently needed. However, development of combo-vaccines is often faced with intra-vaccine interference which could compromise vaccination outcomes. Here we present an approach to overcoming this problem using a microneedle array patch (MAP)-based combo-vaccine with minimum intra-vaccine interference. Methods: Vaccine-laden dissolving MAPs were fabricated using a two-step micro-molding process with polyvinyl alcohol as major excipient. A partition-loading strategy was adopted to ensure spatially segregated distribution of a split-virus Flu vaccine and recombinant prefusion protein of RSV in separate MAP sectors. Serum samples from BALB/c mice post-vaccination were assessed for titers of binding and neutralizing antibodies against the viruses. Live virus challenge studies were carried out to assess the protection efficacy of the MAP-based vaccines. Results: Although i.m. administered standalone Flu and RSV vaccines were able to induce strong IgG responses in BALB/c mice, bidirectional intra-vaccine interference was observed when the two vaccines were co-administered in premixed form. However, when the two vaccines were loaded onto nonoverlapping sectors of D-MAPs for intradermal vaccination, the intra-vaccine interference effect was effectively overcome. The partition-loaded MAP-Flu/RSV combo-vaccine elicited antigen-specific IgG with robust virus-neutralizing activity and was strongly efficacious against either virus in challenge studies. Conclusions: Our data provide proof-of-concept evidence for the potential usefulness of partition-loaded MAPs in overcoming a critical barrier in vaccinology and offer a promising platform for future clinical translation.