The aim of this work is to develop a single‐step process to produce hydroxyapatite/polycaprolactone (HAp/PCL) composite filaments for 3D printing of bone scaffolds by fused deposition modeling (FDM). The HAp/PCL composite filaments are produced by hot‐melt extrusion, with direct in situ blending. For practical purposes, the effect of PCL particle size on filament homogeneity and printability is assessed between PCL in powder and pellet form. The effect of HAp content on processing parameters and filament properties is also evaluated. Filament extrudability, homogeneity, and shape consistency improve with increasing HAp content up to a threshold of 40 wt%. Furthermore, an optimal range of the composite melt viscosity for the extrusion process is defined. The produced filaments are successfully 3D printed by FDM and the resulting prototypes show improved compressive modulus and degradation rate with increasing HAp content. A cytocompatibility assay is conducted, which suggests an optimal HAp content to be less than 40 wt% in terms of cell viability, adhesion, and proliferation. The developed method offers several advantages, as it completely avoids the use of toxic solvents and enables the incorporation of very high HAp concentrations, further improving the chances of implementation of FDM for bone tissue regeneration medicine.
Transdermal drug delivery is an attractive non-invasive method offering numerous advantages over the conventional routes of administration. The main obstacle to drug transport is, however, the powerful skin barrier that needs to be modulated, for example, by transdermal permeation enhancers. Unfortunately, there are still only a few enhancers showing optimum properties including low toxicity and reversibility of enhancing effects. For this reason, we investigated a series of new N-alkylmorpholines with various side chains as potential enhancers in an in vitro permeation study, using three model permeants (theophylline, indomethacin, diclofenac). Moreover, electrical impedance, transepidermal water loss, cellular toxicity and infrared spectroscopy measurements were applied to assess the effect of enhancers on skin integrity, reversibility, toxicity and enhancers’ mode of action, respectively. Our results showed a bell-shaped relationship between the enhancing activity and the hydrocarbon chain length of the N-alkylmorpholines, with the most efficient derivatives having 10–14 carbons for both transdermal and dermal delivery. These structures were even more potent than the unsaturated oleyl derivative. The best results were obtained for indomethacin, where particularly the C10-14 derivatives showed significantly stronger effects than the traditional enhancer Azone. Further experiments revealed reversibility in the enhancing effect, acceptable toxicity and a mode of action based predominantly on interactions with stratum corneum lipids.
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