Abstract
Transcutaneous administration has the potential to improve therapeutics delivery, providing an approach that is safer and more convenient than traditional alternatives, while offering the opportunity for improved therapeutic efficacy through sustained/controlled drug release. To this end, a microneedle materials platform is demonstrated for rapid implantation of controlled-release polymer depots into the cutaneous tissue. Arrays of microneedles composed of drug-loaded poly(lactide-co-glycolide) (PLGA) microparticles or solid PLGA tips are prepared with a supporting and rapidly water-soluble poly(acrylic acid) (PAA) matrix. Upon application of microneedle patches to the skin of mice, the microneedles perforate the stratum corneum and epidermis. Penetration of the outer skin layers is followed by rapid dissolution of the PAA binder on contact with the interstitial fluid of the epidermis, implanting the microparticles or solid polymer microneedles in the tissue, which are retained following patch removal. These polymer depots remain in the skin for weeks following application and sustain the release of encapsulated cargos for systemic delivery. To show the utility of this approach the ability of these composite microneedle arrays to deliver a subunit vaccine formulation is demonstrated. In comparison to traditional needle-based vaccination, microneedle delivery gives improved cellular immunity and equivalent generation of serum antibodies, suggesting the potential of this approach for vaccine delivery. However, the flexibility of this system should allow for improved therapeutic delivery in a variety of diverse contexts.
Highlights
Compared to more traditional routes such as oral administration and hypodermic injection, transcutaneous drug delivery through chemical permeation of the skin, iontophoresis, ultrasound, microneedle treatment, or various other strategies has the potential to provide many practical and clinical advantages.[1]
We hypothesized that such a platform would provide rapid administration through brief microneedle application while enabling combined bolus and long-term dosing of cargos released from cutaneously implanted poly(acrylic acid) (PAA) and PLGA depots, respectively
The composite structure allows for simple tuning of extended cargo release kinetics through selection of PLGA copolymer ratio and molecular weight or bolus delivery upon needle disintegration through encapsulation in the PAA matrix
Summary
Compared to more traditional routes such as oral administration and hypodermic injection, transcutaneous drug delivery through chemical permeation of the skin, iontophoresis, ultrasound, microneedle treatment, or various other strategies has the potential to provide many practical and clinical advantages.[1] Relative to parenteral injection, transcutaneous delivery is noninvasive, potentially allowing for rapid, pain-free administration either by minimally trained health care providers, or through self-administration.[2,3] Transcutaneous delivery systems may reduce the generation of dangerous medical waste and inhibit the spread of disease known to occur through needle-reuse and needlebased injury.[4,5] Further, dry storage of systems designed for topical application may provide enhanced drug stability, enabling transport of environmentally sensitive biological therapeutics without the need for refrigeration. These composite microneedle designs provide the ability for rapid administration leading to cutaneous implantation of controlled release depots for either bolus or sustained combinatorial release of therapeutics for various potential applications including vaccine delivery, as demonstrated here
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