Nanocarriers are heavily researched as drug delivery vehicles capable of sequestering antineoplastic agents and then releasing their contents at the desired location. The feasibility of using such carriers stems from their ability to produce a multimodel delivery system whereby passive, ligand and triggered targeting can be applied in the fight against cancer. Passive targeting capitalizes on the leaky nature of tumor tissue which allows for the extravasation of particles with a size smaller than 0.5 µm into the tumors. Ligand targeting utilizes the concept of receptor-mediated endocytosis and involves the conjugation of ligands onto the surface of nanoparticles, while triggered targeting involves the use of external and internal stimuli to release the carriers contents upon reaching the diseased location. In this review, micelles and liposomes have been considered due to the promising results they have shown in vivo and in vitro and their potential for advancements into clinical trials. Thus, this review focuses on the most recent advancements in the field of micellar and liposomal drug delivery and considers the synergistic effect of passive- and ligand-targeting strategies, and the use of ultrasound in triggering drug release at the tumor site.

No abstract

Objective To gain insight into the molecular mechanisms underlying the early stages of vocal fold extracellular matrix (ECM) remodeling after a mid-membranous injury resulting from the use of human amniotic epithelial cells (hAEC), as a novel regenerative medicine cell-based therapy. Methods Vocal folds of six female, New Zealand White rabbits were bilaterally injured. Three rabbits had immediate bilateral direct injection of 1 × 106 hAEC in 100 µl of saline solution (hAEC) and three with 100 µl of saline solution (controls, CTR). Rabbits were euthanized 6 weeks after injury. Proteomic analyses (in-gel trypsin protein digestion, LC–MS/MS, protein identification using Proteome Discoverer and the Uniprot Oryctolagus cuniculus (Rabbit) proteome) and histological analyses were performed. Results hAEC treatment significantly increased the expression of ECM proteins, elastin microfibril interface-located protein 1 (EMILIN-1) and myocilin that are primarily involved in elastogenesis of blood vessels and granulation tissue. A reactome pathway analysis showed increased activity of the anchoring fibril formation by collagen I and laminin, providing mechanical stability and activation of cell signaling pathways regulating cell function. hAEC increased the abundance of keratin 1 indicating accelerated induction of the differentiation programming of the basal epithelial cells and, thereby, improved barrier function. Lastly, upregulation of Rab GDP dissociation inhibitor indicates that hAEC activate the vesicle endocytic and exocytic pathways, supporting the exosome-mediated activation of cell–matrix and cell-to-cell interactions. Conclusions This pilot study suggests that injection of hAEC into an injured rabbit vocal fold favorably alters ECM composition creating a microenvironment that accelerates differentiation of regenerated epithelium and promotes stabilization of new blood vessels indicative of accelerated and improved repair.

Utilizing a novel processing method of PEEK foam that produces hierarchical mesoporosity, we explore the use of hydroxyapatite (HA)/PEEK composites for mimicking the structure of human bone. The effect of HA content and processing parameters on the porosity, and interconnective network are studied with respect to the corresponding morphology, mechanical properties, and ultimately the cell viability. Having achieved hierarchical structuration with pore sizes ranging from approx. a hundred nanometers all the way to a few hundred microns, the HA/PEEK composites produced desirable mechanical properties and promising cell proliferation. A strong correlation was not seen with HA loading and the resulting properties, but a combination of the HA loading and variance in porosity is shown to be significant. The development and analysis of this bone mimic structure opens up the potential for this processing method and material as a treatment to bone injuries and bone diseases.

There are reciprocal interactions between epithelial cells and underlying basement membrane. The resemblance of biomaterials to native basement membrane is thus critical for their success when used to regenerate epithelium-containing organs. Particularly, the use of nanofibers and the incorporation of basement membrane proteins may mimic both biophysical and biochemical properties of basement membrane, respectively. Herein we tested how electrospun polycaprolactone/ heparin fibers with and without adsorbed laminin and collagen IV proteins affect epithelial cell functions. We found that airway epithelial cells attached, migrated, and proliferated on all scaffolds but protein-functionalized fibers promoted higher attachment, quicker migration, and increased proliferation. Fibers were then integrated on polyethylene scaffolds and cultured at an air-liquid interface. The detection of secretory and ciliated cell markers was higher in cells on polyethylene with fibers. These findings demonstrate that electrospun fibers incite beneficial epithelial cell responses and can be used in the fabrication of bioengineered functional epithelia.