Abstract:DNA vaccines are simple to produce and can generate strong cellular and humoral immune response, making them attractive vaccine candidates. However, a major shortcoming of DNA vaccines is their poor immunogenicity when administered intramuscularly. Transcutaneous immunization (TCI) via microneedles is a promising alternative delivery route to enhance the vaccination efficacy. A novel dissolving microneedle array (DMA)-based TCI system loaded with cationic liposomes encapsulated with hepatitis B DNA vaccine and… Show more
“…vaccination with a much lower dose of DNA, due to the inability to deliver 100 % of the DNA cargo from the dissolving MN tips. This suggests that not only does the developed MN delivery system successfully induce an antigen-specific immune response in this animal model but it also has the advantage of being a dose-sparing delivery system [56].…”
Section: Via Dissolving Mn Arraysmentioning
confidence: 98%
“…Qiu et al (2015) developed a dissolving microneedle system, fabricated from PVP, encapsulating cationic liposomes loaded with plasmid DNA encoding the middle envelope proteins of hepatitis B virus and adjuvant CpG oligodeoxynucleotide molecules (10 μg of each). The potency of this system for eliciting antigen-specific immune responses was evaluated by comparison to i.m.…”
The advent of microneedle (MN) technology has provided a revolutionary platform for the delivery of therapeutic agents, particularly in the field of gene therapy. For over 20 years, the area of gene therapy has undergone intense innovation and progression which has seen advancement of the technology from an experimental concept to a widely acknowledged strategy for the treatment and prevention of numerous disease states. However, the true potential of gene therapy has yet to be achieved due to limitations in formulation and delivery technologies beyond parenteral injection of the DNA. Microneedle-mediated delivery provides a unique platform for the delivery of DNA therapeutics clinically. It provides a means to overcome the skin barriers to gene delivery and deposit the DNA directly into the dermal layers, a key site for delivery of therapeutics to treat a wide range of skin and cutaneous diseases. Additionally, the skin is a tissue rich in immune sentinels, an ideal target for the delivery of a DNA vaccine directly to the desired target cell populations. This review details the advancement of MN-mediated DNA delivery from proof-of-concept to the delivery of DNA encoding clinically relevant proteins and antigens and examines the key considerations for the improvement of the technology and progress into a clinically applicable delivery system.
“…vaccination with a much lower dose of DNA, due to the inability to deliver 100 % of the DNA cargo from the dissolving MN tips. This suggests that not only does the developed MN delivery system successfully induce an antigen-specific immune response in this animal model but it also has the advantage of being a dose-sparing delivery system [56].…”
Section: Via Dissolving Mn Arraysmentioning
confidence: 98%
“…Qiu et al (2015) developed a dissolving microneedle system, fabricated from PVP, encapsulating cationic liposomes loaded with plasmid DNA encoding the middle envelope proteins of hepatitis B virus and adjuvant CpG oligodeoxynucleotide molecules (10 μg of each). The potency of this system for eliciting antigen-specific immune responses was evaluated by comparison to i.m.…”
The advent of microneedle (MN) technology has provided a revolutionary platform for the delivery of therapeutic agents, particularly in the field of gene therapy. For over 20 years, the area of gene therapy has undergone intense innovation and progression which has seen advancement of the technology from an experimental concept to a widely acknowledged strategy for the treatment and prevention of numerous disease states. However, the true potential of gene therapy has yet to be achieved due to limitations in formulation and delivery technologies beyond parenteral injection of the DNA. Microneedle-mediated delivery provides a unique platform for the delivery of DNA therapeutics clinically. It provides a means to overcome the skin barriers to gene delivery and deposit the DNA directly into the dermal layers, a key site for delivery of therapeutics to treat a wide range of skin and cutaneous diseases. Additionally, the skin is a tissue rich in immune sentinels, an ideal target for the delivery of a DNA vaccine directly to the desired target cell populations. This review details the advancement of MN-mediated DNA delivery from proof-of-concept to the delivery of DNA encoding clinically relevant proteins and antigens and examines the key considerations for the improvement of the technology and progress into a clinically applicable delivery system.
“…In particular, this kind of MPMAs loaded with hepatitis B virus DNAs could effectively deliver DNA vaccine into skin, inducing effective immune response toward the desired pathway establishing robust immunity against HBV in mouse model. 46 By comparison, Bouwstra's group demonstrated that encapsulation of model antigen OVA into cationic DOTPA/CpG OND-liposomes had a beneficial effect on the quality of the antibody response in mice after intranodal or i.d. immunization via needle injection but, notably, impaird proper delivery of antigen and adjuvant to the lymph nodes when the formulations are administered intra-nasally or transcutaneously at the site pre-treated by metal MAs (4 £ 4 microneedles with a length of 300 mm).…”
To overcome drawbacks of current injection vaccines, such as causing needle phobia, needing health professionals for inoculation, and generating dangerous sharps wastes, researchers have designed novel vaccines that are combined with various microneedle arrays (MAs), in particular, with the multifunctional particle-constructed MAs (MPMAs). MPMAs prove able to enhance vaccine stability through incorporating vaccine ingredients in the carrier, and can be painlessly inoculated by minimally trained workers or by selfadministration, leaving behind no metal needle pollution while eliciting robust systemic and mucosal immunity to antigens, thanks to delivering vaccines to cutaneous or mucosal compartments enriched in professional antigen-presenting cells (APCs). Especially, MPMAs can be easily integrated with functional molecules fulfilling targeting vaccine delivery or controlling immune response toward a Th1 or Th2 pathway to generate desired immunity against pathogens. Herein, we introduce the latest research and development of various MPMAs which are a novel but promising vaccine adjuvant delivery system (VADS).
“…20,[29][30][31] The stability of inactivated viruses and protein antigens has been established in certain dissolvable microneedle formulations [32][33][34] however, little investigation has been done to determine whether incorporation into dissolvable microneedles has any influence on the stability of DNA or to directly compare the suitability of different polymer matrices to deliver nucleic acid cargo. This is perhaps surprising given that some polymers have been known to form hydrogen bonds with DNA and have been reported to be capable of enhancing gene delivery in their own right.…”
Section: Introductionmentioning
confidence: 99%
“…18 Microneedles can be defined as a series of sharp microprojections, ranging up to 1000 mm in length, which are capable of piercing the outer barrier of the skin, the stratum corneum (SC), to create transient pores to the viable epidermal and dermal layers. 19 Microneedle-mediated DNA vaccines have demonstrated efficacy in mouse models against pathogenic diseases, such as hepatitis B 20 and influenza, 21 and perhaps more impressively against antigen-expressing tumors. 22,23 Initial gene delivery studies focused on applying DNA solutions to the skin, followed by application of solid microneedles, 24,25 however variability in dosing and high wastage of cargo have seen a shift toward the use of coated microneedles.…”
DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays. However, to date little work has directly compared the suitability of different dissolvable matrices for formulation of DNA-loaded microneedles. Therefore, the current study examined the ability of 4 polymers to formulate mechanically robust, functional DNA loaded dissolvable microneedles. Additionally, complexation of DNA to a cationic delivery peptide, RALA, prior to incorporation into the dissolvable matrix was explored as a means to improve transfection efficacies following release from the polymer matrix. Our data demonstrates that DNA is degraded following incorporation into PVP, but not PVA matrices. The complexation of DNA to RALA prior to incorporation into polymers resulted in higher recovery from dissolvable matrices, and increased transfection efficiencies in vitro. Additionally, RALA/DNA nanoparticles released from dissolvable PVA matrices demonstrated up to 10-fold higher transfection efficiencies than the corresponding complexes released from PVP matrices, indicating that PVA is a superior polymer for this microneedle application.
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