Liposomes and Extracellular Vesicles as Drug Delivery Systems: A Comparison of Composition, Pharmacokinetics, and Functionalization

Abstract

Over the past decades, lipid-based nanoparticle drug delivery systems (DDS) have caught the attention of researchers worldwide, encouraging the field to rapidly develop improved ways for effective drug delivery. One of the most prominent examples is liposomes, which are spherical shaped artificial vesicles composed of lipid bilayers and able to encapsulate both hydrophilic and hydrophobic materials. At the same time, biological nanoparticles naturally secreted by cells, called extracellular vesicles (EVs), have emerged as promising more complex biocompatible DDS. In this review paper, the differences and similarities in the composition of both vesicles are evaluated, and critical mediators that affect their pharmacokinetics are elucidate. Different strategies that have been assessed to tweak the pharmacokinetics of both liposomes and EVs are explored, detailing the effects on circulation time, targeting capacity, and cytoplasmic delivery of therapeutic cargo. Finally, whether a hybrid system, consisting of a combination of only the critical constituents of both vesicles, could offer the best of both worlds is discussed. Through these topics, novel leads for further research are provided and, more importantly, gain insight in what the liposome field and the EV field can learn from each other.

Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents

“…Liposomes which are artificial spherical vesicles prepared from naturally derived phospholipids are the most widely investigated and well-established drug delivery carriers used in clinics to treat various cancers due to their biocompatibility, specifically being non-immunogenic, non-toxic, and biodegradable. In addition, liposomes serve as sustained release systems providing protection against degradation and increased the time in circulation (Moosavian et al, 2021;van der Koog et al, 2021). In this sense, our group recently demonstrated that liposome encapsulated DSF a relatively extended half-life in serum and a significantly increased anticancer efficacy in in vitro and in vivo breast cancer mouse models (Liu et al, 2014).…”

Bioactive Scaffolds Integrated with Liposomal or Extracellular Vesicles for Bone Regeneration

“…Due to their amphiphilic properties, liposomes form an aqueous inner phase surrounded by lipophilic bilayer(s) that can encapsulate hydrophilic molecules in the inner phase and hydrophobic molecules in the bilayer(s). Liposomes have been widely applied as DDS to deliver chemicals, proteins, peptides, and genetic molecules because of their biocompatible nature and capability to accommodate high content of payloads protecting from degradation [13,15]. There exist commercial liposomal therapeutics in clinical applications, indicating excellent biocompatibility and versatility as DDS [13,15].…”

“…Liposomes have been widely applied as DDS to deliver chemicals, proteins, peptides, and genetic molecules because of their biocompatible nature and capability to accommodate high content of payloads protecting from degradation [13,15]. There exist commercial liposomal therapeutics in clinical applications, indicating excellent biocompatibility and versatility as DDS [13,15]. Biomaterial scaffolds incorporating liposomes have been developed to synergize therapeutic effects and mechanical supports for efficient bone regeneration.…”

“…EVs by themselves or as engineered carriers for the delivery of payloads are an active area of research in the field of bone regenerative medicine [10][11][12]. Compared with liposomes, EVs offer more excellent biocompatibility, efficient cellular internalization, and specific tissue targeting capability [14,15]. Many constituents of exosomes reflect their cellular origin, including nucleic acids, proteins, lipids, and metabolites [53,55,56].…”

“…[14]. Due to their inherent capacity to carry bioactive molecules, EVs are emerging as an advanced substitute for synthetic liposomes [15] as well as a novel cell-free therapy [16] for bone regeneration. Although ex-vivo cultivated cells have been considered an important component of BTE, a cell-free BTE system has recently begun to gain attention because it can avoid undesirable side effects such as limited autologous cells, low survival rate, tumorigenesis, and immune-rejection issues [16,17].…”