With several advances in microfabrication techniques, a variety of microneedle (MN) systems with distinct mechanisms of delivery have been developed to overcome the stratum corneum barrier and used for delivery of small molecules and macromolecules. The physicochemical properties of the small molecule drugs, salt forms, excipients, and other formulation factors have been shown to influence drug permeability. Intradermal and transdermal delivery of macromolecules, including therapeutic peptides and proteins, vaccines, and the synergistic effect of combined enhancement techniques in addition to MN treatment are described in this review. Temporarily disrupting the skin micropore closure mechanisms increased the micropore lifetime and transdermal delivery efficiency. The safety issues of transdermal and intradermal delivery have also been highlighted in this review. Micropore formation in the skin is much less invasive than hypodermic needle use with respect to pain sensation and skin re-sealing.
Device manufacturers are investing in R&D and design strategies to support the transdermal drug delivery industry, valued at $13.5 billion in 2013 and expected to reach $21.7 billion by 2018 according to the Micro-market Monitor. Microneedles are not limited to any specific class of drugs. According to “The Microneedles for Transdermal and Intradermal Drug Delivery, 2014-2030” report, more than 70% of the products in development are patches incorporating solid or dissolvable needles, the rest are hollow microneedle arrays that employ the use of a syringe. With several new microneedle-based therapeutic product launches by the end of this decade, the report concludes that the overall market for microneedle-based delivery devices will reach annual sales of 485 million units by 2030. Microneedle-based drug delivery has the potential to be a transformative technology for the delivery of biologics and vaccines. It may provide enhanced therapeutic profiles for therapeutics and vaccines. It allows for the administration of lower levels of drugs to achieve the same therapeutic endpoints. Additionally, microneedles provide an alternative to traditional needles. This industry provides a means to overcome one of the biggest barriers to patient compliance for the treatment of chronic diseases and routine vaccination. The variation in the microneedle types could also prove useful in controlling the kinetics of vaccine release. Such complex variations will further support the use of LSR technology and will be instrumental in the further evolution in the effectiveness and use of transdermal delivery systems.
Website references: https://www.mdtmag.com/article/2016/07/microneedle-patches-enable-superior-drug-delivery
Journal Articles: https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.6b00859
Gas vesicle nanoparticles (GVNPs) are hollow, buoyant protein organelles produced by the extremophilic microbe Halobacterium sp. NRC-1 and are being developed as bioengineerable and biocompatible antigen and drug-delivery systems (DDS). Dynamic light scattering measurements of purified GVNP suspensions showed a mean diameter of 245 nm. In vitro diffusion studies using Yucatan miniature pig skin showed GVNP permeation to be enhanced after MN-treatment compared to untreated skin. GVNPs were found to be nontoxic to mammalian cells (human kidney and rat mycocardial myoblasts). These findings support the use of GVNPs as DDS for intradermal/transdermal permeation of protein- and peptide-based drugs.
Journal Article: DOI: https://doi.org/10.4049/jimmunol.1302743
Shigella is one of the leading pathogens contributing to the vast pediatric diarrheal disease burden in low-income countries. No licensed vaccine is available, and the existing candidates are only partially effective and serotype specific. Shigella type III secretion system proteins IpaB and IpaD, which are conserved across Shigella spp., are candidates for a broadly protective, subunit-based vaccine. In this study, we investigated the immunogenicity and protective efficacy of IpaB and IpaD administered intradermally (i.d.) with a double-mutant of the Escherichia coli heat-labile enterotoxin (dmLT) adjuvant using microneedles. Different dosage levels of IpaB and IpaD, with or without dmLT, were tested in mice. Vaccine delivery into the dermis, recruitment of neutrophils, macrophages, dendritic cells, and Langerhans cells, and colocalization of vaccine Ag within skin-activated APC were demonstrated through histology and immunofluorescence microscopy. Ag-loaded neutrophils, macrophages, dendritic cells, and Langerhans cells remained in the tissue at least 1 wk. IpaB, IpaD, and dmLT-specific serum IgG- and IgG-secreting cells were produced following i.d. immunization. The protective efficacy was 70% against Shigella flexneri and 50% against Shigella sonnei. Similar results were obtained when the vaccine was administered intranasally, with the i.d. route requiring 25–40 times lower doses. Distinctively, IgG was detected in mucosal secretions; secretory IgA, as well as mucosal and systemic IgA Ab-secreting cells, were seemingly absent. Vaccine-induced T cells produced IFN-γ, IL-2, TNF-α, IL-17, IL-4, IL-5, and IL-10. These results demonstrate the potential of i.d. vaccination with IpaB and IpaD to prevent Shigella infection and support further studies in humans.
