Novel bilayer dissolving microneedle arrays with concentrated PLGA nano-microparticles for targeted intradermal delivery: Proof of concept
Polymeric microneedle (MN) arrays continue to receive growing attention due to their ability to bypass the skin's stratum corneum barrier in a minimally-invasive fashion and achieve enhanced transdermal drug delivery and “targeted” intradermal vaccine administration. In this research work, we fabricated biodegradable bilayer MN arrays containing nano - microparticles for targeted and sustained intradermal drug delivery. For this study, model drug (vitamin D3, VD3)-loaded PLGA nano- and microparticles (NMP) were prepared by a single emulsion solvent evaporation method with 72.8% encapsulation of VD3. The prepared NMP were directly mixed 20% w/v poly(vinyl pyrrolidone) (PVP) gel, with the mixture filled into laser engineered micromoulds by high-speed centrifugation (30 min) to concentrate NMP into MN shafts. The particle size of PLGA NMP ranged from 300 nm to 3.5 μm and they retained their particle size after moulding of bilayer MN arrays. The relatively wide particle size distribution of PLGA NMP was shown to be important in producing a compact structure in bilayer conical, as well as pyramidal, MN, as confirmed by scanning electron microscopy. The drug release profile from PLGA NMP was tri-phasic, being sustained over 5 days. The height of bilayer MN arrays was influenced by the weight ratio of NMP and 20% w/v PVP. Good mechanical and insertion profiles (into a skin simulant and excised neonatal porcine skin) were confirmed by texture analysis and optical coherence tomography, respectively. Ex vivo intradermal neonatal porcine skin penetration of VD3 NMP from bilayer MN was quantitatively analysed after cryostatic skin sectioning, with 74.2 ± 9.18% of VD3 loading delivered intradermally. The two-stage novel processing strategy developed here provides a simple and easy method for localising particulate delivery systems into dissolving MN. Such systems may serve as promising means for controlled transdermal delivery and targeted intradermal administration.