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Transdermal delivery of antigen and chemokine proteins that activates the maturation of skin dendritic cells (DCs) and direct the migration of activated DCs to lymph and spleen is an important alternative to conventional vaccines. However, stratum corneum forms a barrier to skin penetration. The poor cellular uptake of free antigens and chemokines also limits transcutaneous immunization efficacy. In this work, a pair of iontophoresis-driven microneedle patches is constructed, of which, two kinds of outer membrane vesicles (OMVs) derived from Escherichia coli transformed by plasmid encoding gp100 (IPMN-G) and chemokine ligand 21 (IPMN-C) are incorporated within microneedles, respectively. The topical application of IPMN-G and IPMN-C shows the effectiveness of transdermally delivering gp100 and CCL21 secreting vesicles to skin DCs. With iontophoresis as a driving generator, the release and uptake of transgenic OMVs in target cells are significantly enhanced, with transcutaneous immunization initiated. The in vivo applications of IPMN-G and IPMN-C with a 12 h interval retard the progression and prevent the occurrence of tumor spheroids. IPMN-GC is shown as a promising triplatform in engineering transgenic OMV-incorporated microneedles, driven by iontophoresis into a transcutaneous vaccine, providing a noninvasive system for the transdermal delivery of antigen and chemokine proteins for transcutaneous vaccination-meditated immunotherapy.

Transdermal delivery of antigen and chemokine proteins that activates the maturation of skin dendritic cells (DCs) and direct the migration of activated DCs to lymph and spleen is an important alternative to conventional vaccines. However, stratum corneum forms a barrier to skin penetration. The poor cellular uptake of free antigens and chemokines also limits transcutaneous immunization efficacy. In this work, a pair of iontophoresis-driven microneedle patches is constructed, of which, two kinds of outer membrane vesicles (OMVs) derived from Escherichia coli transformed by plasmid encoding gp100 (IPMN-G) and chemokine ligand 21 (IPMN-C) are incorporated within microneedles, respectively. The topical application of IPMN-G and IPMN-C shows the effectiveness of transdermally delivering gp100 and CCL21 secreting vesicles to skin DCs. With iontophoresis as a driving generator, the release and uptake of transgenic OMVs in target cells are significantly enhanced, with transcutaneous immunization initiated. The in vivo applications of IPMN-G and IPMN-C with a 12 h interval retard the progression and prevent the occurrence of tumor spheroids. IPMN-GC is shown as a promising triplatform in engineering transgenic OMV-incorporated microneedles, driven by iontophoresis into a transcutaneous vaccine, providing a noninvasive system for the transdermal delivery of antigen and chemokine proteins for transcutaneous vaccination-meditated immunotherapy.

Transdermal delivery of antigen and chemokine proteins that activates the maturation of skin dendritic cells (DCs) and direct the migration of activated DCs to lymph and spleen is an important alternative to conventional vaccines. However, stratum corneum forms a barrier to skin penetration. The poor cellular uptake of free antigens and chemokines also limits transcutaneous immunization efficacy. In this work, a pair of iontophoresis-driven microneedle patches is constructed, of which, two kinds of outer membrane vesicles (OMVs) derived from Escherichia coli transformed by plasmid encoding gp100 (IPMN-G) and chemokine ligand 21 (IPMN-C) are incorporated within microneedles, respectively. The topical application of IPMN-G and IPMN-C shows the effectiveness of transdermally delivering gp100 and CCL21 secreting vesicles to skin DCs. With iontophoresis as a driving generator, the release and uptake of transgenic OMVs in target cells are significantly enhanced, with transcutaneous immunization initiated. The in vivo applications of IPMN-G and IPMN-C with a 12 h interval retard the progression and prevent the occurrence of tumor spheroids. IPMN-GC is shown as a promising triplatform in engineering transgenic OMV-incorporated microneedles, driven by iontophoresis into a transcutaneous vaccine, providing a noninvasive system for the transdermal delivery of antigen and chemokine proteins for transcutaneous vaccination-meditated immunotherapy.

Transdermal delivery of antigen and chemokine proteins that activates the maturation of skin dendritic cells (DCs) and direct the migration of activated DCs to lymph and spleen is an important alternative to conventional vaccines. However, stratum corneum forms a barrier to skin penetration. The poor cellular uptake of free antigens and chemokines also limits transcutaneous immunization efficacy. In this work, a pair of iontophoresis-driven microneedle patches is constructed, of which, two kinds of outer membrane vesicles (OMVs) derived from Escherichia coli transformed by plasmid encoding gp100 (IPMN-G) and chemokine ligand 21 (IPMN-C) are incorporated within microneedles, respectively. The topical application of IPMN-G and IPMN-C shows the effectiveness of transdermally delivering gp100 and CCL21 secreting vesicles to skin DCs. With iontophoresis as a driving generator, the release and uptake of transgenic OMVs in target cells are significantly enhanced, with transcutaneous immunization initiated. The in vivo applications of IPMN-G and IPMN-C with a 12 h interval retard the progression and prevent the occurrence of tumor spheroids. IPMN-GC is shown as a promising triplatform in engineering transgenic OMV-incorporated microneedles, driven by iontophoresis into a transcutaneous vaccine, providing a noninvasive system for the transdermal delivery of antigen and chemokine proteins for transcutaneous vaccination-meditated immunotherapy.

Transdermal delivery of antigen and chemokine proteins that activates the maturation of skin dendritic cells (DCs) and direct the migration of activated DCs to lymph and spleen is an important alternative to conventional vaccines. However, stratum corneum forms a barrier to skin penetration. The poor cellular uptake of free antigens and chemokines also limits transcutaneous immunization efficacy. In this work, a pair of iontophoresis-driven microneedle patches is constructed, of which, two kinds of outer membrane vesicles (OMVs) derived from Escherichia coli transformed by plasmid encoding gp100 (IPMN-G) and chemokine ligand 21 (IPMN-C) are incorporated within microneedles, respectively. The topical application of IPMN-G and IPMN-C shows the effectiveness of transdermally delivering gp100 and CCL21 secreting vesicles to skin DCs. With iontophoresis as a driving generator, the release and uptake of transgenic OMVs in target cells are significantly enhanced, with transcutaneous immunization initiated. The in vivo applications of IPMN-G and IPMN-C with a 12 h interval retard the progression and prevent the occurrence of tumor spheroids. IPMN-GC is shown as a promising triplatform in engineering transgenic OMV-incorporated microneedles, driven by iontophoresis into a transcutaneous vaccine, providing a noninvasive system for the transdermal delivery of antigen and chemokine proteins for transcutaneous vaccination-meditated immunotherapy.

Diabetes chronic wound is a severe and frequently occurring medical issue in patients with diabetes that often leads to more serious complications. Microneedles (MNs) can be used for wound healing as they can effectively pierce the epidermis and inject drugs into the wound tissue. However, common MN patches cannot provide sufficient skin adhesion to prevent detachment from the wound area. Inspired by the barb hangnail microstructure of porcupine quills, a porcupine quill-like multilayer MN patch with an adhesive back patching for tissue adhesion and diabetic wound healing was designed. Sodium hyaluronate-modified CaO2 nanoparticles and metformin (hypoglycemic agent) were loaded into the polycaprolactone tips of MNs, endowing them with exceptional antibacterial ability and hypoglycemic effect. A flexible and adhesive back patching was formed by polyacrylamide-polydopamine/Cu2+ composite hydrogel, which ensures that the MN patches do not peel off from the application sites and reduce bacterial infection. The bioinspired multilayer structure of MN patches exhibits satisfactory mechanical and antibacterial properties, which is a potential multifunctional dressing platform for promoting wound healing. Statement of significance: The porcupine quill-like microneedles (MNs) with PAM-PDA/Cu2+ (PPC) composite hydrogel back patching have been fabricated, which can enhance the adhesion property of MNs to the skin through a physical interlock of multilayer MNs and chemical bonding of hydrogel patching. CaO2-HA NPs and metformin were loaded into the polycaprolactone tips of MNs, endowing them with the exceptional antibacterial ability and hypoglycemic effect, which could accelerate diabetic wound healing. As a safe and effective strategy in transdermal delivery of drugs, the as-fabricated flexible multilayer MN patch with good antibacterial, hypoglycemic, and biocompatibility has been used to promote the healing of diabetic wound by releasing oxygen and inhibiting inflammation at, SCOPUS: ar.j, info:eu-repo/semantics/published