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

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.

Polydopamine-Coated Liposomes for Methylene Blue Delivery in Anticancer Photodynamic Therapy: Effects in 2D and 3D Cellular Models.

Photodynamic therapy (PDT) is a therapeutic option for cancer, in which photosensitizer (PS) drugs, light, and molecular oxygen generate reactive oxygen species (ROS) and induce cell death. First- and second-generation PSs presented with problems that hindered their efficacy, including low solubility. Thus, second-generation PSs loaded into nanocarriers were produced to enhance their cellular uptake and therapeutic efficacy. Among other compounds investigated, the dye methylene blue (MB) showed potential as a PS, and its photodynamic activity in tumor cells was reported even in its nanocarrier-delivered form, including liposomes. Here, we prepared polydopamine (PDA)-coated liposomes and efficiently adsorbed MB onto their surface. lipoPDA@MB vesicles were first physico-chemically characterized and studies on their light stability and on the in vitro release of MB were performed. Photodynamic effects were then assessed on a panel of 2D- and 3D-cultured cancer cell lines, comparing the results with those obtained using free MB. lipoPDA@MB uptake, type of cell death induced, and ability to generate ROS were also investigated. Our results show that lipoPDA@MB possesses higher photodynamic potency compared to MB in both 2D and 3D cell models, probably thanks to its higher uptake, ROS production, and apoptotic cell death induction. Therefore, lipoPDA@MB appears as an efficient drug delivery system for MB-based PDT.

Polymer Encapsulated Liposomes for Oral Co-Delivery of Curcumin and Hydroxytyrosol.

Curcumin (Cur) is a hydrophobic polyphenol from the rhizome of Curcuma spp., while hydroxytyrosol (HT) is a water-soluble polyphenol from Olea europaea. Both show outstanding antioxidant properties but suffer from scarce bioavailability and low stability in biological fluids. In this work, the co-encapsulation of Cur and HT into liposomes was realized, and the liposomal formulation was improved using polymers to increase their survival in the gastrointestinal tract. Liposomes with different compositions were formulated: Type 1, composed of phospholipids and cholesterol; Type 2, also with a PEG coating; and Type 3 providing an additional shell of Eudragit® S100, a gastro-resistant polymer. Samples were characterized in terms of size, morphology, ζ-potential, encapsulation efficiency, and loading capacity. All samples were subjected to a simulated in vitro digestion and their stability was investigated. The Eudragit®S100 coating demonstrated prevention of early releases of HT in the mouth and gastric phases, while the PEG shell reduced bile salts and pancreatin effects during the intestinal digestion. In vitro antioxidant activity showed a cumulative effect for Cur and HT loaded in vesicles. Finally, liposomes with HT concentrations up to 40 µM and Cur up to 4.7 µM, alone or in combination, did not show cytotoxicity against Caco-2 cells.

Liposomes containing nanoparticles: preparation and applications.

The impetuous development of nanotechnology over the past two decades has enabled the production of a plethora of nanomaterials with outstanding optical, magnetic, electrical, catalytic and mechanical properties. The versatility of these materials attracted attention from the very beginning in the most disparate sectors of science and technology. The application of nanomaterials in the biological and biomedical fields soon benefited from the interaction with liposomes, which increased their biocompatibility and biostability. Liposomes indeed are versatile self-assembling supramolecular (nano)structures constituted of an aqueous core enclosed by a lipid bilayer, able to host hydrophobic and hydrophilic cargo, and with superior biocompatibility and great similarity with the biological membranes. The result is the construction of hybrid nanoscale architectures, in which nanoparticles (NPs) are allocated either in the aqueous core, in the palisade of the lipid bilayer or on the outer surface of the vesicles. In the first part of this review, the principal methods for the preparation of NP-loaded liposomes are carefully illustrated in a tutorial manner. In the second part, an overview of the great potentialities deriving from the conjugation of liposomes with NPs is presented. In each paragraph, the main characteristics of the most notable classes of NPs, the related issues, and the advantages arising from their association with liposomes are shown. Here, the most significant research works in literature for each kind of system are presented.

Easy Preparation of Liposome@PDA Microspheres for Fast and Highly Efficient Removal of Methylene Blue from Water.

Mussel-inspired chemistry was usefully exploited here with the aim of developing a high-efficiency, environmentally friendly material for water remediation. A micro-structured material based on polydopamine (PDA) was obtained by using liposomes as templating agents and was used for the first time as an adsorbent material for the removal of methylene blue (MB) dye from aqueous solutions. Phospholipid liposomes were made by extrusion and coated with PDA by self-polymerization of dopamine under simple and mild conditions. The obtained Liposome@PDA microspheres were characterized by DLS and Zeta potential analysis, TEM microscopy, and FTIR spectroscopy. The effects of pH, temperature, MB concentration, amount of Liposome@PDA, and contact time on the adsorption process were investigated. Results showed that the highest adsorption capacity was obtained in weakly alkaline conditions (pH = 8.0) and that it could reach up to 395.4 mg g-1 at 298 K. In addition, adsorption kinetics showed that the adsorption behavior fits a pseudo-second-order kinetic model well. The equilibrium adsorption data, instead, were well described by Langmuir isotherm. Thermodynamic analysis demonstrated that the adsorption process was endothermic and spontaneous (ΔG0 = -12.55 kJ mol-1, ΔH0 = 13.37 kJ mol-1) in the investigated experimental conditions. Finally, the applicability of Liposome@PDA microspheres to model wastewater and the excellent reusability after regeneration by removing MB were demonstrated.