Lipid-Based Nanotechnology: Liposome

Abstract

Over the past several decades, liposomes have been extensively developed and used for various clinical applications such as in pharmaceutical, cosmetic, and dietetic fields, due to its versatility, biocompatibility, and biodegradability, as well as the ability to enhance the therapeutic index of free drugs. However, some challenges remain unsolved, including liposome premature leakage, manufacturing irreproducibility, and limited translation success. This article reviews various aspects of liposomes, including its advantages, major compositions, and common preparation techniques, and discusses present U.S. FDA-approved, clinical, and preclinical liposomal nanotherapeutics for treating and preventing a variety of human diseases. In addition, we summarize the significance of and challenges in liposome-enabled nanotherapeutic development and hope it provides the fundamental knowledge and concepts about liposomes and their applications and contributions in contemporary pharmaceutical advancement.

Keywords: disease treatments; drug delivery; liposome.

Figure 1

Chemical structure of phosphatidic acid (R = H). The red-labeled portion indicates the headgroup of the phosphatidic acid.

Figure 2

Chemical structures of DOTMA, DOTAP, and DDAB.

Figure 3

Chemical structure of cholesterol.

Figure 4

Demonstration of the use of the thin film hydration method to generate liposomes.

Figure 5

Illustration of the reverse phase evaporation method to produce liposomes [46]. Schematic representation of the main stages of the reverse-phase evaporation method. Lipids are dissolved in organic solvent (A), and the formation of inverted micelles is observed (B). The addition of aqueous media (buffer), followed by emulsification of the solution, favors the formation a homogeneous dispersion of a W/O microemulsion (C). With the final elimination of the organic solvent (by using rotary evaporation, under vacuum), a viscous gel is formed in the solution, which finally collapses to form liposomes (D) (LUVs).

Figure 6

Solvent injection method for liposome preparation [46]. A composition of lipids dissolved in alcohol solution is injected into an aqueous phase (buffer) (A). The dilution of ethanol in the water solution favors the self-assembly of lipid components and the formation of bilayer planar fragments (B). Finally, the ethanol evaporation (depletion) favors the fusion of the lipids’ fragments and the formation of closed unilamellar vesicles (SUL and LUV) (C).

Figure 7

Illustration of microfluidic mixing and formation of liposomes [54].

Figure 8

Illustration of tumor cell penetration with a peptide-decorated liposome [136]. (A) The Structure of peptide-decorated liposomes under different pH environments. (B) Within tumors, the peptide-decorated liposomes could target integrin α_Vβ₃ and initiate internalization and further intertumoral activities.