Permeation of antigen protein-conjugated nanoparticles and live bacteria through microneedle-treated mouse skin
Authors: Kumar A, Li X, Sandoval MA, Rodriguez BL, Sloat BR, Cui Z Published Date June 2011 Volume 2011:6 Pages 1253 - 1264 DOI: http://dx.doi.org/10.2147/IJN.S20413
Amit Kumar, Xinran Li, Michael A Sandoval, B Leticia Rodriguez, Brian R Sloat, Zhengrong Cui University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX, USA
Background: The present study was designed to evaluate the extent to which pretreatment with microneedles can enhance skin permeation of nanoparticles in vitro and in vivo. Permeation of live bacteria, which are physically nanoparticles or microparticles, through mouse skin pretreated with microneedles was also studied to evaluate the potential risk of microbial infection.
Methods and results: It was found that pretreatment of mouse skin with microneedles allowed permeation of solid lipid nanoparticles, size 230 nm, with ovalbumin conjugated on their surface. Transcutaneous immunization in a mouse skin area pretreated with microneedles with ovalbumin nanoparticles induced a stronger antiovalbumin antibody response than using ovalbumin alone. The dose of ovalbumin antigen determined whether microneedle-mediated transcutaneous immunization with ovalbumin nanoparticles induced a stronger immune response than subcutaneous injection of the same ovalbumin nanoparticles. Microneedle treatment permitted skin permeation of live Escherichia coli, but the extent of the permeation was not greater than that enabled by hypodermic injection.
Conclusion: Transcutaneous immunization on a microneedle-treated skin area with antigens carried by nanoparticles can potentially induce a strong immune response, and the risk of bacterial infection associated with microneedle treatment is no greater than that with a hypodermic injection.
Pretreatment with microneedles allowed skin permeation of nanoparticles with antigen protein conjugated onto them. Transcutaneous immunization onto a skin area pretreated with microneedles with the protein antigen carried by nanoparticles induced a stronger antigen-specific antibody response than using the protein antigen alone. The antigen dose used to immunize the mice determined whether the microneedle-mediated immunization can induce a stronger immune response than when the same anoparticle-based vaccine formulation was dosed by subcutaneous injection. Damage to the physical integrity of the skin caused by microneedles, although reversible, may permit permeation of live bacteria through the skin, but the risk of bacterial infection associated with microneedles is not expected to be higher than that associated with injection using a hypodermic needle.
With the increasing interest in nanoparticles as a drug delivery system, more research on skin permeation of nanoparticles prior to or after microneedle treatment is warranted.
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