Drug delivery systems are created to achieve the desired therapeutic effect of a specific pharmaceutical compound. Numerous drawbacks and side effects such as unfavorable pharmacokinetics, lack of tissue selectivity, immunogenicity, increased systemic clearance and toxicity, have been observed for currently available drug delivery systems (DDSs). The use of natural and artificial extracellular vesicles (EVs) in drug delivery may help to solve the aforementioned problems faced by different DDSs. Due to their self-origin, small size, flexibility, the presence of multiple adhesive molecules on their surfaces as well as their function as biomolecules carriers, EVs are the perfect candidates for DDSs. Currently, several drug delivery systems based on EVs have been proposed. While the great potential of these particles in targeted drug delivery has been recognized in cancer, hepatitis C, neurodegenerative diseases, inflammatory states etc., this field is still in the early stage of development. Unfortunately, the use of EVs from natural sources (cell cultures, body fluids) results in numerous problems in terms of the heterogeneity of isolated vesicle population as well as the method of isolation thereof, which may influence vesicle composition and properties. Therefore, there is a significant need for the synthesis of artificial EV-based DDSs under strictly controlled laboratory conditions and from well-defined biomolecules (proteins and lipids). Vesicle-mimetic delivery systems, characterized by properties similar to natural EVs, will bring new opportunities to study the mechanisms of DDS internalization and their biological activity after delivering their cargo to a target cell.
16 February 2016 in Expert Opinion on Drug Delivery
Objectives: Bone infections are treated with antibiotics administered intravenously, antibiotic-releasing bone cements or collagen sponges placed directly in the infected area. These approaches ren...
Cancer cells are known to release extracellular vesicles that often promote disease development and progression. The present study investigated the protein content and glycosylation pattern of ectosomes released in vitro by a human primary uveal melanoma Mel202 cell line. Ectosomes released by Mel202 cells were isolated from conditioned media using sequential centrifugation, and a nano-LC-MS/MS approach was used to determine their protein content. Subsequently, proteins from ectosomes, the whole cell extracts, and the membrane fractions were probed with a panel of lectins using Western blotting and flow cytometry to reveal characteristic glycan structures. As many as 2527 unique proteins were identified, and many of them are known to be involved in cancer cell proliferation and altered metabolism, tumor invasion, metastasis, or drug resistance. Lectin-based studies revealed a distinct glycosylation pattern between Mel202-derived ectosomes and the parental cell membranes. Selective enrichment of ectosomal proteins with bisected complex type N-glycans and α2,6-linked sialic acids may be significant for ectosome formation and sequestration. Differences in the surface glycosylation of Mel202 cells and ectosomes supports recent findings that the budding of ectosomes occurs within strictly determined fragments of the plasma membrane, and thus ectosomes contain a unique protein and glycan composition.
1 January 2019 in International Journal of Medical Sciences
Background: Platelet-derived microvesicles (PMVs), shed from platelet surface membranes, constitute the majority of circulating microvesicles and have been implicated in procoagulant, pro-inflammatory and pro-atherosclerotic effects. Our aim was to compare plasma PMVs numbers in relation to platelet reactivity during dual antiplatelet therapy (DAPT) with various P2Y12 adenosine diphosphate (ADP) receptor antagonists.