Biodegradable Defined Shaped Printed Polymer Microcapsules for Drug Delivery.

This work describes the preparation and characterization of printed biodegradable polymer (polylactic acid) capsules made in two different shapes: pyramid and rectangular capsules about 1 and 11 µm in size. Obtained core-shell capsules are described in terms of their morphology, loading efficiency, cargo release profile, cell cytotoxicity, and cell uptake. Both types of capsules showed monodisperse size and shape distribution and were found to provide sufficient stability to encapsulate small water-soluble molecules and to retain them for several days and ability for intracellular delivery. Capsules of 1 µm size can be internalized by HeLa cells without causing any toxicity effect. Printed capsules show unique characteristics compared with other drug delivery systems such as a wide range of possible cargoes, triggered release mechanism, and highly controllable shape and size.

Magnetically responsive layer-by-layer microcapsules can be retained in cells and under flow conditions to promote local drug release without triggering ROS production.

Nanoengineered vehicles have the potential to deliver cargo drugs directly to disease sites, but can potentially be cleared by immune system cells or lymphatic drainage. In this study we explore the use of magnetism to hold responsive particles at a delivery site, by incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) into layer-by-layer (LbL) microcapsules. Microcapsules with SPIONs were rapidly phagocytosed by cells but did not trigger cellular ROS synthesis within 24 hours of delivery nor affect cell viability. In a non-directional cell migration assay, SPION containing microcapsules significantly inhibited movement of phagocytosing cells when placed in a magnetic field. Similarly, under flow conditions, a magnetic field retained SPION containing microcapsules at a physiologic wall shear stress of 0.751 dyne cm-2. Even when the SPION content was reduced to 20%, the majority of microcapsules were still retained. Dexamethasone microcrystals were synthesised by solvent evaporation and underwent LbL encapsulation with inclusion of a SPION layer. Despite a lower iron to volume content of these structures compared to microcapsules, they were also retained under shear stress conditions and displayed prolonged release of active drug, beyond 30 hours, measured using a glucocorticoid sensitive reporter cell line generated in this study. Our observations suggest use of SPIONs for magnetic retention of LbL structures is both feasible and biocompatible and has potential application for improved local drug delivery.

In-situ NIR-laser mediated bioactive substance delivery to single cell for EGFP expression based on biocompatible microchamber-arrays.

Controlled drug delivery and gene expression is required for a large variety of applications including cancer therapy, wound healing, cell migration, cell modification, cell-analysis, reproductive and regenerative medicine. Controlled delivery of precise amounts of drugs to a single cell is especially interesting for cell and tissue engineering as well as therapeutics and has until now required the application of micro-pipettes, precisely placed dispersed drug delivery vehicles, or injections close to or into the cell. Here we present surface bound micro-chamber arrays able to store small hydrophilic molecules for prolonged times in subaqueous conditions supporting spatiotemporal near infrared laser mediated release. The micro-chambers (MCs) are composed of biocompatible and biodegradable polylactic acid (PLA). Biocompatible gold nanoparticles are employed as light harvesting agents to facilitate photothermal MC opening. The degree of photothermal heating is determined by numerical simulations utilizing optical properties of the MC, and confirmed by Brownian motion measurements of laser-irradiated micro-particles exhibiting similar optical properties like the MCs. The amount of bioactive small molecular cargo (doxycycline) from local release is determined by fluorescence spectroscopy and gene expression in isolated C2C12 cells via enhanced green fluorescent protein (EGFP) biosynthesis.

Electrospun poly(lactic acid) fibers containing novel chlorhexidine particles with sustained antibacterial activity.

The treatment of persistent infections often requires a high local drug concentration and sustained release of antimicrobial agents. This paper proposes the use of novel electrospinning of poly(lactic acid) (PLA) fibers containing uncoated and encapsulated chlorhexidine particles. Chlorhexidine particles with a mean (SD) diameter of 17.15 ± 1.99 µm were fabricated by the precipitation of chlorhexidine diacetate with calcium chloride. Layer-by-layer (LbL) encapsulation of the chlorhexidine particles was carried out to produce encapsulated particles. The chlorhexidine particles had a high chlorhexidine content (90%), and when they were electrospun into PLA fibers a bead-in-string structure was obtained. The chlorhexidine content in the fibers could be tuned and a sustained release over 650 h was produced, via chlorhexidine particle encapsulation. Chlorhexidine release was governed by the polyelectrolyte multilayer encapsulation as demonstrated by SEM and confocal imaging. The incorporation of uncoated and encapsulated chlorhexidine particles (0.5% and 1% wt/wt chlorhexidine) into the fibers did not cause toxicity to healthy fibroblasts or affect cell adhesion to the fibers over a period of 5 days. The chlorhexidine-containing fibers also demonstrated sustained antibacterial activity against E. coli via an agar diffusion assay and broth transfer assay. Therefore, the chlorhexidine-containing PLA fibers may be useful in the treatment of persistent infections in medicine and dentistry.