Novel bilayer dissolving microneedle arrays with concentrated PLGA nano-microparticles for targeted intradermal delivery: Proof of concept

Abstract

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 D, VD)-loaded PLGA nano- and microparticles (NMP) were prepared by a single emulsion solvent evaporation method with 72.8% encapsulation of VD. 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 (30min) to concentrate NMP into MN shafts. The particle size of PLGA NMP ranged from 300nm to 3.5μm 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 5days. 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 VD NMP from bilayer MN was quantitatively analysed after cryostatic skin sectioning, with 74.2±9.18% of VD 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.

Design, Formulation, and Evaluation of Novel Dissolving Microarray Patches Containing Rilpivirine for Intravaginal Delivery

“…This study builds upon work previously carried out in our research group, where we described the formulation, development and in vivo testing of dissolving microarray patches (MAPs) incorporating RPV LA for intradermal delivery . MAPs are micrometer‐scale devices, which have undergone extensive research in the fields of intradermal drug and vaccine delivery and have also been used in combination with nanosuspensions but had never before been used in the delivery of a LA nanosuspension, the potential of which we had previously theorized . An integral part of the present study, carried out with colleagues in PATH, involved conducting preliminary market research, early in the design concept phase, to inform the potential acceptability of MAPs for delivery of HIV PrEP intravaginally.…”

Current Advances in Sustained Release Microneedles

“…[44][45][46][47] Another strategy that can enable dissolving microneedles to release the payloads in a controlled manner is to combine nano-and microparticle technologies. 48,49 Vora et al fabricated PVP-based microneedles loaded with a mixture of poly (lactic-co-glycolic acid) (PLGA) nanoparticles and microparticles. 48 The developed system showed good mechanical and In the first step, the microneedles quickly dissolved and released the free drug as well as another drug encapsulated in PLGA microparticles.…”

Novel nanosuspension‐based dissolving microneedle arrays for transdermal delivery of a hydrophobic drug

“…Dissolving microneedles efficiently deliver therapeutic agents through the dissolution of their biocompatible polymer matrices after penetration into the skin (Vora, Donnelly, et al, ; Vora, Sita, & Vavia, ). DMNs rely on the water solubility of both the loaded drug and the polymer matrix.…”