Engineered PLGA-PVP/VA based formulations to produce electro-drawn fast biodegradable microneedles for labile biomolecule delivery

Abstract

Biodegradable polymer microneedles (MNs) are recognized as non-toxic, safe and stable systems for advanced drug delivery and cutaneous treatments, allowing a direct intradermal delivery and in some cases a controlled release. Most of the microneedles found in the literature are fabricated by micromolding, which is a multistep thus typically costly process. Due to industrial needs, mold-free methods represent a very intriguing approach in microneedle fabrication. Electro-drawing (ED) has been recently proposed as an alternative fast, mild temperature and one-step strategy to the mold-based techniques for the fabrication of poly(lactic-co-glycolic acid) (PLGA) biodegradable MNs. In this work, taking advantage of the flexibility of the ED technology, we engineered microneedle inner microstructure by acting on the water-in-oil (W/O) precursor emulsion formulation to tune drug release profile. Particularly, to promote a faster release of the active pharmaceutical ingredient, we substituted part of PLGA with poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP/VA), as compared to the PLGA alone in the matrix material. Moreover, we introduced lecithin and maltose as emulsion stabilizers. Microneedle inner structural analysis as well as collagenase entrapment efficiency, release and activity of different emulsion formulations were compared to reach an interconnected porosity MN structure, aimed at providing an efficient protein release profile. Furthermore, MN mechanical properties were examined as well as its ability to pierce the stratum corneum on a pig skin model, while the drug diffusion from the MN body was monitored in an in vitro collagen-based dermal model at selected time points.

Hydrogelation tunability of bioinspired short peptides

“…Samples, at two different times of aggregation (t = 0 and 6 days), were dropped on stub at 400 mM concentrations and introduced into chamber of field emission scanning (Nova NanoSem 450 FEI/ThermoFisher Scientific), to obtain Sem micrographs at 3.00 and 5.00 kV in high vacuum mode, with an Everhart Thornley Detector (ETD) and the Through the Lens Detector (TLD), as previously reported. [61][62][63][64][65]…”

Potential of Microneedle Systems for COVID-19 Vaccination: Current Trends and Challenges

“…Dissolving microneedles (DMNs) are miniature needles made of polymers such as polylactic-co-glycolic acid (PLGA), polylactic acid (PLA), and polyglycolic acid (PGA) that dissolve in the skin to deliver encapsulated medicines, leaving no sharp waste [ 56 , 216 ]. DMN arrays are now overlaid onto patches to aid in their implantation into the skin [ 10 , 217 ].…”

“…The core–shell microstructure of the dissolving microneedles is created by assembling three separate components of the microneedles, including a microneedle shell, a microneedle cap, and a dry drug or vaccine core, utilizing a 3D manufacturing method [ 46 , 55 , 266 ]. The cap and base layer, which are composed of the same biodegradable polymer, poly(d,l-lactide-co-glycolide) (PLGA), encase the medication or vaccine core [ 212 , 216 ]. The drug release may be precisely regulated by adjusting the PLGA shell’s disintegration [ 217 , 219 ].…”

Biomaterials for Regenerative Medicine in Italy: Brief State of the Art of the Principal Research Centers

“…The Centre for Advanced Biomaterials for Health Care of IIT and the Department of Chemical, Materials and Industrial Production Engineering (University of Naples Federico II) have designed microneedles based on PLLA/PLGA microparticles and a PVP-made tip for controlled intradermal drug delivery. These devices are biodegradable and compatible with skin tissue both in vitro and in vivo [ 146 , 147 , 148 ]. Their work is also focused on the development of drug-delivery systems based on PLGA, PCL, PEG and other hydrogels [ 149 , 150 , 151 , 152 , 153 ] ( Table 5 ).…”