Endogenous Lipid Carriers—Bench-to-Bedside Roadblocks in Production and Drug Loading of Exosomes

Abstract

Exosomes are cell-derived, nano-sized extracellular vesicles comprising a lipid bilayer membrane that encapsulates several biological components, such as nucleic acids, lipids, and proteins. The role of exosomes in cell–cell communication and cargo transport has made them promising candidates in drug delivery for an array of diseases. Despite several research and review papers describing the salient features of exosomes as nanocarriers for drug delivery, there are no FDA-approved commercial therapeutics based on exosomes. Several fundamental challenges, such as the large-scale production and reproducibility of batches, have hindered the bench-to-bedside translation of exosomes. In fact, compatibility and poor drug loading sabotage the possibility of delivering several drug molecules. This review provides an overview of the challenges and summarizes the potential solutions/approaches to facilitate the clinical development of exosomal nanocarriers.

Therapeutic Intervention of Neuroinflammatory Alzheimer Disease Model by Inhibition of Classical Complement Pathway with the Use of Anti-C1r Loaded Exosomes

“…Exosome-liposome hybrids would provide use of the bene ts of both vesicles -improved targeted ability, biocompatibility, and drug loading [29], [39].…”

“…Though T-ALZ01 is a possible therapeutic, its inability to cross the blood-brain barrier warranted the use of an alternative method of drug delivery. Exosomes are nanosized, extracellular vesicles characterized by a lipid bilayer encompassing biological components [ 27 ]–[ 29 ]. Exosomes demonstrate specific targeting capabilities to the cell type from which they were derived, thus, microglia derived exosomes were utilized to ensure targeted delivery of T-ALZ01 to the microglia [ 27 ]–[ 29 ].…”

“…Exosomes are nanosized, extracellular vesicles characterized by a lipid bilayer encompassing biological components [ 27 ]–[ 29 ]. Exosomes demonstrate specific targeting capabilities to the cell type from which they were derived, thus, microglia derived exosomes were utilized to ensure targeted delivery of T-ALZ01 to the microglia [ 27 ]–[ 29 ]. Exosomes as a drug delivery tool would prove beneficial in reducing economic and social burden, making the administration of therapeutic easier on patient and doctor.…”

Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application

“…(2) The state of the source cells, modifications upstream and downstream, have an impact on the composition and characteristics of exosomes, resulting in diverse therapeutic outcomes. Therefore, controlling the stability of the source cell culture environment and developing gentle and effective exosome processing techniques could help reduce variation between batches whilst maintaining stable exosome structure and properties [ 215 ]. (3) Existing isolation techniques can only produce small amounts of exosomes, which are costly to produce on a large scale [ 216 ].…”

Ferroptosis-related exosomal non-coding RNAs: promising targets in pathogenesis and treatment of non-malignant diseases

“…A subsequent folding in LSEs leads to multivesicular endosome (MVEs) containing intraluminal vesicles (ILVs), with cytoplasmic components entering ILVs. MVEs can either merge with lysosomes for degradation or release ILVs via exosome shedding through the cell membrane ( Figure 1 ) ( Alidadi et al, 2023 ; Richards et al, 2023 ). The origin of ncRNAs, including miRNAs, lncRNAs, and circular RNAs, is a pivotal aspect of exosomal composition.…”