Polydopamine-Modified Liposomes: Preparation and Recent Applications in the Biomedical Field

Abstract

Polydopamine (PDA) is a bioinspired polymer that has unique and desirable properties for emerging applications in the biomedical field, such as extraordinary adhesiveness, extreme ease of functionalization, great biocompatibility, large drug loading capacity, good mucopenetrability, strong photothermal capacity, and pH-responsive behavior. Liposomes are consolidated and attractive biomimetic nanocarriers widely used in the field of drug delivery for their biocompatibility and biodegradability, as well as for their ability to encapsulate hydrophobic, hydrophilic, and amphiphilic compounds, even simultaneously. In addition, liposomes can be decorated with appropriate functionalities for targeted delivery purposes. Thus, combining the interesting properties of PDA with those of liposomes allows us to obtain multifunctional nanocarriers with enhanced stability, biocompatibility, and functionality. In this review, a focus on the most recent developments of liposomes modified with PDA, either in the form of polymer layers trapping multiple vesicles or in the form of PDA-coated nanovesicles, is proposed. These innovative PDA coatings extend the application range of liposomes into the field of biomedical applications, thereby allowing for easier functionalization with targeting ligands, which endows them with active release capabilities and photothermal activity and generally improves their interaction with biological fluids. Therefore, hybrid liposome/PDA systems are proposed for surface-mediated drug delivery and for the development of nanocarriers intended for systemic and oral drug delivery, as well as for multifunctional nanocarriers for cancer therapy. The main synthetic strategies for the preparation of PDA-modified liposomes are also illustrated. Finally, future prospects for PDA-coated liposomes are discussed, including the suggestion of potential new applications, deeper evaluation of side effects, and better personalization of medical treatments.

Figure 1

Illustration of the first steps of the mechanism of dopamine oxidation to form PDA and possible derived structures. Reproduced from ref (3) under Creative Commons license.

Figure 2

Main properties of the PDA.

Figure 3

Main applications of PDA in the biomedical field.

Figure 4

Illustration of the use of PDA as a coating for supported liposome layers. The coatings thus obtained have improved interactions with cells and are useful as surface coatings in surface-mediated drug delivery applications.

Figure 5

Sketch depicting the possibility of easily functionalizing PDA coatings with amines and thiols via Michael addition or Schiff’s base reaction.

Figure 6

Schematic illustration of the preparation of DOX-loaded liposomes coated with PDA and further functionalization with folic acid. Reprinted with permission from ref (20). Copyright 2019 Elsevier.

Figure 7

Illustration of the ability of the PDA coating to modulate the release of the cargoes embedded into the liposomes, as well as to entrap and release compounds from the PDA surface.

Figure 8

Sketch illustrating the possibility of exploiting the PDA coating around liposomes to obtain pH- or light-stimulus-responsive systems.

Figure 9

Picture showing the mucopenetrating behavior of the liposomes. Conventional liposomes (A) usually unable to cross the mucus layer, whereas PDA-coated liposomes (B) succeed in reaching the underlying layers.

Figure 10

Illustration of the implementation of PEG or PDA coatings to liposomes as a strategy to improve their efficacy in the oral administration of anticancer drugs. Reproduced from ref (31) under Creative Commons license.

Figure 11

Picture showing the ability of the PDA coating to generate stealth liposomes by reducing/modulating the adsorption of proteins onto their surface once they are in contact with biological fluids.

Figure 12

Panel 1: Dependence of the extent of lysis induced in red blood cells following incubation with liposome (Lipo)@PDA on the PDA shell thickness and vesicle concentration. Panel 2: (A–C) Percentage of red blood cell lysis induced by PEG- and PDA-coated liposomes (Lipo@PEG and Lipo@PDA, respectively) at different final lipid concentrations and increasing PDA shell thickness; (D) photographs of PDA-coated liposomes obtained at increasing polymerization time; and (E) physicochemical characterization of PDA-coated liposomes in terms of diameter, polymer coating thickness, polydispersity index, and polymerization reaction yield (%). Panel 2 reprinted with permission from ref (11). Copyright 2024 Elsevier.

Figure 13

Use of the PDA coating to obtain multifunctional nanocarriers by simultaneously exploiting its properties.

Figure 14

Preparation strategies for hybrid liposome/PDA systems: (A) platforms consisting of a liposome layer adhered to a suitably functionalized support and subsequently coated with PDA by in situ polymerization of DA; Lipo@PDA obtained via in situ polymerization of DA (B) in a liposomal suspension and (C) in the presence of liposomes featuring an amphiphilic dopamine derivative in the lipid bilayer.

Figure 15

Illustration of the assembly of liposomes-adsorbed PLL-precoated substrates with a PDA layer following exposure to myoblast cells. Reprinted with permission from ref (24). Copyright 2011 American Chemical Society.

Figure 16

Sketch depicting the procedure for preparing Lipo@PDA starting from vesicles with OD in the bilayer. (i) A DA solution is mixed with the liposomes and (ii) allowed to react; then (iii) the sample is purified through dialysis. Reprinted from ref (25) under Creative Commons license.