Liposomes or Extracellular Vesicles: A Comprehensive Comparison of Both Lipid Bilayer Vesicles for Pulmonary Drug Delivery

Abstract

The rapid and non-invasive pulmonary drug delivery (PDD) has attracted great attention compared to the other routes. However, nanoparticle platforms, like liposomes (LPs) and extracellular vesicles (EVs), require extensive reformulation to suit the requirements of PDD. LPs are artificial vesicles composed of lipid bilayers capable of encapsulating hydrophilic and hydrophobic substances, whereas EVs are natural vesicles secreted by cells. Additionally, novel LPs-EVs hybrid vesicles may confer the best of both. The preparation methods of EVs are distinguished from LPs since they rely mainly on extraction and purification, whereas the LPs are synthesized from their basic ingredients. Similarly, drug loading methods into/onto EVs are distinguished whereby they are cell- or non-cell-based, whereas LPs are loaded via passive or active approaches. This review discusses the progress in LPs and EVs as well as hybrid vesicles with a special focus on PDD. It also provides a perspective comparison between LPs and EVs from various aspects (composition, preparation/extraction, drug loading, and large-scale manufacturing) as well as the future prospects for inhaled therapeutics. In addition, it discusses the challenges that may be encountered in scaling up the production and presents our view regarding the clinical translation of the laboratory findings into commercial products.

Donepezil-Loaded Nanocarriers for the Treatment of Alzheimer’s Disease: Superior Efficacy of Extracellular Vesicles Over Polymeric Nanoparticles

“…This could also have impacted the surface charge of EVs-DNZ due to changes in the proteins and/or lipids of the membrane exposed to the surface of the vesicles. 63 , 64 The zeta potential for NPs-PLA-PEG showed an overall negative charge without modification after drug loading. Low values of zeta potential (−40 mV) for both nanoformulations indicate reduced aggregation by the electrostatic repulsion of particles helping to increase physical stability.…”

Piperlongumine inhibits proliferation and oncogenic MYCN expression in chemoresistant metastatic retinoblastoma cells directly and through extracellular vesicles

“…It has been shown that PL is internalized, undergoes intracellular hydrolysis, and binds to the intracellular protein GSTP1 [ 68 ]. Also, multiple studies demonstrate cell-based drug internalization and loading into EVs, to generate EV-drug carriers [ 69 , 70 ]. To the best of our knowledge, this is the first time a natural product is shown to reduce the pro-oncogenic contents of retinoblastoma EVs with the ability to reduce proliferation in recipient cells.…”

Pulmonary inhalation for disease treatment: Basic research and clinical translations

“…They have similar properties to liposomes (e.g., structure, composition, drug loading, protection capacity, particle size, and pharmaco kinetics and pharmaco dynamics(PKPD), among others); however, they have limitations such as the inability to be mass-produced and a high cost. Hybrid vesicles synthesized from liposomes and extracellular vesicles have been developed as potential new delivery vehicles for pulmonary inhalation drug delivery [ 183 ].

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