Highly Porous and Drug-Loaded Amorphous Solid Dispersion Microfiber Scaffolds of Indomethacin Prepared by Melt Electrowriting

Abstract

Melt electrowriting (MEW) is an additive manufacturing technology enabling the production of highly porous microfiber scaffolds, suggested in particular for use in biomedical applications, including drug delivery. Indomethacin (IND) is a nonselective anti-inflammatory drug, for which sublingual delivery could offer advantages such as rapid absorption by the veins in the mouth floor while overcoming the side effects of peroral delivery such as damage to the gastrointestinal mucosa barrier. This study introduces MEW as a processing method to obtain rapid-dissolving drug-releasing scaffolds, containing IND as a model drug, for sublingual drug delivery applications. For this, an amorphous solid dispersion (ASD) of IND in combination with a poly(2-oxazoline)-based amphiphilic triblock copolymer excipient is introduced, enabling ultra-high drug loading. We prepared highly porous, melt electrowritten drug-loaded scaffolds with different polymer/IND w/w ratios up to 1:2 and assessed their morphology, amorphicity, and IND release rate. The results show completely amorphous dispersion of the polymer and drug after MEW processing resulting in smooth and uniform fibers and rapid dissolution of the drugloaded scaffold. These first water-soluble melt electrowritten IND-loaded microfiber scaffolds break ground as a model for rapid sublingual delivery of ultra-high drug-loaded ASDs.

Self-Nanoformulating Poly(2-oxazoline) and Poly(2-oxazine) Copolymers Based Amorphous Solid Dispersions as Microneedle Patch: A Formulation Study

“…It has been shown previously that a range of similar POx-based triblock copolymers are excellent crystallization inhibitors and nanocrystal stabilizer, not only for CUR. [34,[36][37][38] If crystallization occurred, it would adversely affect the structural integrity of the MNs' surfaces. [10] Instead, the solid amorphous dispersion formed from CUR exhibit suitable mechanical properties to release from the molds and yield structurally well-formed MNs.…”

Materials and Strategies to Enhance Melt Electrowriting Potential

“…[34][35][36][37] Additionally, MEW's ability to process drug-loaded structures with controlled release properties have been demonstrated, providing another perspective that combines with the scaffold design possibilities. [38,39] Many of the polymers processed by MEW so far have a history of clinical use, with poly(𝜖-caprolactone) (PCL) being the gold standard polymer used due to both its excellent processability and broad used within tissue engineering and regenerative medicine applications. [40] All the biomedical applications of MEW have been described in detail in different reviews.…”

“…More recently, Keßler and colleagues investigated the processing of a poly(2‐oxazoline)s (POx)‐based amphiphilic triblock copolymer (MeOzi‐PentOx‐MeOzi) for developing a drug delivery system. [ 39 ] Well‐ordered structures with up to 20 stacked layers and fibers of around 49 µm were processed at 155 °C. Samples show a fast dissolution behavior in PBS media, suitable for drug release applications.…”

Improving Infection Resistance in Tissue Engineered Scaffolds for Tensile Applications Using Vancomycin‐Embedded Melt Electrowritten Scaffolds

“…[10] Coupling precision biomimetic scaffold design technology with advanced antibiotic-releasing biomaterials presents a promising new avenue in MEW research. Several recent studies have proposed inclusions of pharmaceutical additives to MEW scaffolds [11] for applications in sublingual drug delivery [12] and the treatment of pelvic organ prolapse (POP). [13] Drug loading, defined as the mass ratio of drug to drug-loaded scaffolds is an important parameter in determining the clinical translation of such scaffolds.…”

“…Currently, most drug loaded scaffolds have low drug loading of maximum 10% w/w, ranging anywhere between 1 and 10% w/w. [3,12,14,15] Developing high drug loaded scaffolds is still a challenge. Herein, we report for the first time the incorporation of high doses of vancomycin loading (5, 10, and 25% w/w) on MEW scaffolds designed for tensile loading regimes, applicable toward the development of ligament and tendon tissues, among others.…”