Mechanical Disruption of Skin Barrier for Vaccine Delivery

Abstract

Delivering vaccines into skin offers an appealing alternative to needle-based administration for immunization. Besides the benefit of directly delivering vaccines into immunologically competent skin, cutaneous immunization provides the benefits of patient compliance and dose sparing. Vaccine delivery into skin, however, is limited by the barrier of stratum corneum, the outermost layer of skin. A variety of technologies have been developed to permeabilize the stratum corneum to enhance vaccine entry into skin. This review provides a summary of some of these technologies that are based on mechanical disruption of stratum corneum. These include liquid jet injectors, powder injectors, ultrasound, microneedles, abrasive devices, thermal ablation and lasers. An overview of the principles of these technologies, their ability to deliver vaccines and experience in clinical applications is discussed.

A miniature shock wave driven micro‐jet injector for needle‐free vaccine/drug delivery

“…Several physical methods of drug delivery into skin were envisaged and tried. The strategies included delivery of heavy particulate drug (Liu and Kendall, 2007;Menezes et al, 2012;Nakada et al, 2008), operation of needleless jet injectors (Arora et al, 2007;Han and Yoh, 2010;Menezes et al, 2009), patches with arrays of drug coated micro-projections (Kendall, 2006;Raphael et al, 2010), ultrasound permeabilizers to enhance vaccine diffusion into skin (Mitragotri, 2005b), laser and thermal ablation, and abrasive devices (Mitragotri, 2012;Tagawa et al, 2012). The needle-free micro-jet injectors have the advantage of controlled release to the depth of the dermis with a minimum and recoverable breach of the target.…”

“…The sophisticated devices (Han and Yoh, ; Menezes et al, ; Mitragotri, ; Nakagawa et al, ) coupled with their skilled operators and conducive ambience increase the cost of operation, and may deter their extensive use in global health care for administration of vaccine. Economizing the medical facilities with an intention of extending them to a widespread primary use level, has been a thrust area of research, and a substantial effort is being devoted to achieve this objective worldwide.…”

Dynamic behavior of a spring-powered micronozzle needle-free injector

“…More critical are the inconsistency of formulation penetration and the pool out of liquid on the skin (Mitragotri, 2012). The latter limits intra-and inter-individual reproducibility of the key pharmacokinetics parameters with obvious issues on formulation bioequivalence.…”

“…Needle-free jet injectors have been conceived to minimize pain and inconvenience in parenteral therapy. Invented more than a century ago, liquid jet injectors were used in clinics for mass immunization only in the 1950s (Mitragotri, 2012).…”

Microneedles for drug delivery: trends and progress

“…Several review papers have been published on different types of enhancement techniques (Al-Saidan, 2004;Benson, 2005;Arora et al, 2008;Tanner & Marks, 2008;Banga, 2009;Yadav et al, 2011;Milewski & Mitra, 2012;Mitragotri, 2012;Ukawala Ravikumar & Vasava, 2012;Nalesniak et al, 2013), which outline various uses of chemical enhancers like N-methyl-2-pyrrolidone, a pyrrolidone (Sinha & Kaur, 2000) used in the application of insulin, ibuprofen and flurbiprofen. The applications of these techniques for increasing skin permeability would be useful when delivering drugs transdermally.…”