A Novel Transdermal Protein Delivery Strategy via Electrohydrodynamic Coating of PLGA Microparticles onto Microneedles

Abstract

Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter come with major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. Microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological material directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-encapsulated PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significance increase in anti-OVA specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p >0.05) indicating that the formulations are non-immunogenic. The approach of using EHDA to coat a MN array thus appears to have potential as a novel non-invasive protein delivery strategy.

Recent advances in the formulation of PLGA microparticles for controlled drug delivery

“…As already reported, another innovative application of the MPs involves the use of PLGA MPs incorporated into rapid dissolving microneedle patches (MNPs) for intradermal vaccinations (Angkawinitwong et al 2020).…”

Emerging skin-targeted drug delivery strategies to engineer immunity: A focus on infectious diseases

“…These innovative vaccine-loaded systems have been shown to enhance the immunogenicity of antigens through several different mechanisms, including mimicking pathogens, triggering innate signaling pathways, protecting vaccines from in vivo degradation, improving uptake by APCs, or sustaining the presence of antigens, with or without adjuvants [234][235][236][237]. Although these particulate vaccine systems have been predominantly administered by traditional parenteral injections, they have also synergized with MNAs (e.g., Figure 3) for minimally invasive skin-targeted delivery for efficacious immunization [238][239][240][241].…”

“…Microparticles (MPs) integrating vaccine components have been fabricated from biodegradable polymers (e.g., PLGA) to control the release kinetics of antigens with or without adjuvants [234,251]. They have been incorporated onto coated or into biodissolvable MNAs, or administered by hollow MNAs for controlled intracutaneous vaccine delivery to enable safe and effective immunization methods with improved immunogenicity and adherence [240,252,253]. To this end, MNAs enable rapid administration of vaccine-loaded MPs to cutaneous microenvironments where MPs degrade over time (e.g.…”

Electrospray: More than just an ionization source

“…With this particle size, the obtained powder could become a powerful medical device for oral and pulmonary dosing of encapsulated drugs. Angkawinitwong et al deposited ovalbumin encapsulated in poly(lactide-co-glycolide) nanoparticles onto hydrogel-forming microneedle arrays [185]. As a result, extended release of ovalbumin over 28 days was observed.…”