Insights into Asymmetric Liposomes as a Potential Intervention for Drug Delivery Including Pulmonary Nanotherapeutics

Abstract

Liposome-based drug delivery systems are nanosized spherical lipid bilayer carriers that can encapsulate a broad range of small drug molecules (hydrophilic and hydrophobic drugs) and large drug molecules (peptides, proteins, and nucleic acids). They have unique characteristics, such as a self-assembling bilayer vesicular structure. There are several FDA-approved liposomal-based medicines for treatment of cancer, bacterial, and viral infections. Most of the FDA-approved liposomal-based therapies are in the form of conventional “symmetric” liposomes and they are administered mainly by injection. Arikace® is the first and only FDA-approved liposomal-based inhalable therapy (amikacin liposome inhalation suspension) to treat only adults with difficult-to-treat Mycobacterium avium complex (MAC) lung disease as a combinational antibacterial treatment. To date, no “asymmetric liposomes” are yet to be approved, although asymmetric liposomes have many advantages due to the asymmetric distribution of lipids through the liposome’s membrane (which is similar to the biological membranes). There are many challenges for the formulation and stability of asymmetric liposomes. This review will focus on asymmetric liposomes in contrast to conventional liposomes as a potential clinical intervention drug delivery system as well as the formulation techniques available for symmetric and asymmetric liposomes. The review aims to renew the research in liposomal nanovesicle delivery systems with particular emphasis on asymmetric liposomes as future potential carriers for enhancing drug delivery including pulmonary nanotherapeutics.

Optimization of Nasal Liposome Formulation of Venlafaxine Hydrochloride using a Box-Behnken Experimental Design

“…All factors influencing formulation properties are included based on the results. 20 Three factors and a 3 2 Box-Behnken design (BBD) were used to optimize VLF. The observed responses for the BBD for optimizing VLF-loaded LPs formulation factors that are independent and dependent variables are shown in Table 2 .…”

“…There are different types of LPs, including conventional LPs, niosomes, ethosomes, and transfersomes in drug delivery. 18 , 19 , 20 , 21 Dose dumping, which raises the risk of toxicity, is the main disadvantage of sustained-release formulations. 22 Nasal drug delivery systems based on liposomal formulations have demonstrated unique qualities that enable them to overcome biological barriers and lead to enhanced pharmacodynamics.…”

Asymmetric Lipid Vesicles: Techniques, Applications, and Future Perspectives as an Innovative Drug Delivery System

“…Thus, asymmetric liposomes differ from conventional ones because they have different lipid compositions in the inner and outer layers [ 13 , 14 , 15 ], which seems to be more than the cell membrane lipid structure [ 16 ]. Having different lipids in each leaflet makes them relevant because of the possibility of optimizing the inner and outer layers independently to increase flexibility [ 12 ] and encapsulation efficiency [ 17 , 18 ]. Moreover, the leakage of drugs from the inner leaflet can be reduced, while different lipids can be used in the outer leaflet to enhance drug delivery and vesicle stability [ 17 , 18 ].…”

“…Having different lipids in each leaflet makes them relevant because of the possibility of optimizing the inner and outer layers independently to increase flexibility [ 12 ] and encapsulation efficiency [ 17 , 18 ]. Moreover, the leakage of drugs from the inner leaflet can be reduced, while different lipids can be used in the outer leaflet to enhance drug delivery and vesicle stability [ 17 , 18 ]. The flexible or deformable liposomes have special components such as edge activators (span 80, Tween 20, or ethanol) in the bilayers that decrease the interaction between lipids and favor the mobility of hydrophobic tails; this increases the potential for skin permeation, making it possible to have more compatible vesicular drug delivery systems used to protect many drugs for their biochemical and therapeutic purposes.…”

“…The donor vesicle is formulated as a multi-lamellar vesicle and added to a CD pool, and the acceptor is a unilamellar vesicle with a high-density internalized material. Then both vesicles interact thanks to the CDs that borrow lipids from the donor vesicles and exchange them with the outer layer of the acceptor vesicle [ 17 ].…”