Editors' ChoiceDrug Delivery

Dissolving microneedle vaccination—No magic needled

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Science Translational Medicine  26 Sep 2018:
Vol. 10, Issue 460, eaav0343
DOI: 10.1126/scitranslmed.aav0343


Amphiphilic polymeric microneedles dissolve into nanomicelles that inhibit tumor growth.

There is a satisfying elegance in objects that can seamlessly fulfill multiple functions at once. Dissolving microneedles are a prime example of this because, much like an ice cream cone, they function as both vehicle and payload simultaneously. Dissolving microneedles introduce drugs and vaccines into the epidermis with less pain than traditional needles and do not require a skilled operator to use. A major challenge with the applicability of these next-generation delivery systems is that they are typically formed out of water-soluble sugars and polymers, thus limiting their ability to load many clinically useful compounds that are hydrophobic. To overcome this, Kim et al. designed a new microneedle formulation comprised of amphiphilic blends of polymers that can deliver both hydrophobic and hydrophilic compounds at once.

The authors fabricated pyramid-shaped dissolving microneedles out of two biocompatible polymers, F-127 amphiphilic Pluronic triblock copolymer and polyethylene glycol 6000, using polydimethylsiloxane molds. Hydrophilic ovalbumin model antigen with or without hydrophobic adjuvant TLR7/8 agonist R848 was incorporated into the polymers as payload. Adjuvants, such as R848, boost antitumor immune responses when used alone or alongside antigens in vaccine formulations. Microneedles inserted into the flanks of mice with gentle pressure spontaneously dissolved within 60 min into nanomicelles that colocalized with antigen-presenting cells in lymph nodes. Ovalbumin/R848 microneedle injections resulted in ~10 times the amount of ovalbumin-specific antibodies in the serum than those loaded with ovalbumin alone. In comparison with subcutaneous injections with traditional needles, microneedles generated more antibodies and ~10 times lower concentrations of systemic inflammatory cytokine interleukin-6. In mice bearing E.G7-OVA tumor xenografts, ovalbumin/R848 microneedle treatments retarded tumor growth relative to ovalbumin and mock conditions. Furthermore, when this approach was used as a prophylactic, tumor development was inhibited in mice vaccinated with ovalbumin/R848 microneedles for ~68 days after cancer cell injection.

With the ability to create dissolving microneedles containing both hydrophobic and hydrophilic compounds, scientists may now have the capability to deliver a far greater range of vaccine and drug formulations that spontaneously package into nanomicelles upon injection. Although the results in the idealized models reported here are quite promising, it remains to be seen if polymer-based dissolving microneedles can load sufficient quantities of compounds to be effective in the clinic while retaining mechanical stability. If so, the question of “needle or dissolving microneedle” vaccination may be a painless one to answer.

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