Biomimetic nanoparticles: preparation, characterization and biomedical applications

Abstract

Mimicking nature is a powerful approach for developing novel lipid-based devices for drug and vaccine delivery. In this review, biomimetic assemblies based on natural or synthetic lipids by themselves or associated to silica, latex or drug particles will be discussed. In water, self-assembly of lipid molecules into supramolecular structures is fairly well understood. However, their self-assembly on a solid surface or at an interface remains poorly understood. In certain cases, hydrophobic drug granules can be dispersed in aqueous solution via lipid adsorption surrounding the drug particles as nanocapsules. In other instances, hydrophobic drug molecules attach as monomers to borders of lipid bilayer fragments providing drug formulations that are effective in vivo at low drug-to-lipid-molar ratio. Cationic biomimetic particles offer suitable interfacial environment for adsorption, presentation and targeting of biomolecules in vivo. Thereby antigens can effectively be presented by tailored biomimetic particles for development of vaccines over a range of defined and controllable particle sizes. Biomolecular recognition between receptor and ligand can be reconstituted by means of receptor immobilization into supported lipidic bilayers allowing isolation and characterization of signal transduction steps.

Keywords: antigens; bilayer fragments; cationic lipid; drugs; novel cationic immunoadjuvants; phospholipids; polymeric particles; silica; vesicles.

Figure 1

A) Lipid BF of dioctadecyldimethylammonium bromide (DODAB) or B) sodium dihexadecylphosphate (DHP) or C) DSPC/cholesterol/PEG-DSPE(5000) mixtures at 12 mol% PEG-DSPE(5000) or D) DSPC: cholesterol: ceramide-PEG5000 carrying bacteriorhodopsin. Notes: With exception of micrograph in B) which was obtained by TEM after negatively staining the sample, all micrographs were obtained by cryo-TEM. In C), disks were observed edge-on (arrow) or face-on (arrow head). Bars denote 100 nm. Copyright © 1995 and 1991 American Chemical Society; © 2005 and 2007 Elsevier. Adapted with permission from Carmona-Ribeiro AM, Castuma CE, Sesso A, Schreier S. Bilayer structure and stability in dihexadecyl phosphate dispersions. J Phys Chem. 1991;95:5361–5366. Johansson E, Engvall C, Arfvidsson M, Lundahl P, Edwards K. Development and initial evaluation of PEG-stabilized bilayer disks as novel model membranes. Biophys Chem. 2005;113:183–192. Johansson E, Lundquist A, Zuo S, Edwards K. Nanosized bilayer disks: attractive model membranes for drug partition studies. Biochim Biophys Acta. 2007;1768:1518–1525. Andersson M, Hammarstrom L, Edwards K. Effect of bilayer phase transitions on vesicle structure, and its influence on the kinetics of viologen reduction. J Phys Chem. 1995;99(39):14531–14538. Abbreviations: DHP, sodium dihexadecylphosphate; DODAB, dioctadecyldimethylammonium bromide; DSPE, distearoylphosphatidylethanolamine; PEG, polyethyleneglycol; TEM, transmission electron microscopy.

Figure 2

The interaction between one bilayer vesicle and two particles. ,, – Copyright © 1999 Elsevier. Adapted with permission from Carmona-Ribeiro AM, Lessa MM. Interactions between bilayer vesicles and latex. Colloids Surf A. 1999;153:355–361.

Figure 3

Superior performance of novel DODAB-based adjuvants inducing DTH in mice as compared to alum. The same antigen (Ag) carried by each adjuvant was used for immunization. Ag was carried by DODAB BF at 0.1 mM DODAB (DODAB BF/Ag) or by PSS/DODAB or silica/DODAB particles at 0.01 or 0.05 mM DODAB (PSS/DODAB/Ag or silica/DODAB/Ag), respectively, or by alum (Al(OH)/Ag). After immunization, elicitation of the swelling response was done by injecting Ag alone in the footpad so that % footpad swelling was measured in comparison to alum. Copyright © 2007, 2009 Elsevier. Adapted with permission from Lincopan N, Espíndola NM, Vaz AJ, Carmona-Ribeiro AM. Cationic supported lipid bilayers for antigen presentation. In. J Pharm. 2007;340:216–222. Lincopan N, Espíndola NM, Vaz AJ, et al. Novel immunoadjuvants based on cationic lipid: preparation, characterization and activity in vivo. Vaccine. 2009;27:5760–5771. Lincopan N, Santana MRA, Faquim-Mauro E, da Costa MHB, Carmona-Ribeiro AM. Silica-based cationic bilayers as immunoadjuvants. BMC Biotechnol. 2009;9:article 5. Abbreviations: DODAB, dioctadecyldimethylammonium bromide; PSS, polystyrene sulfate; DTH, delayed-type hypersensibility; BF, bilayer fragments.

Figure 4

A) Encapsulation of amphotericin B particle by a cationic bilayer at high drug to lipid molar ratio; B) Solubilization of amphotericin B at the rim of cationic BF at low drug to lipid molar ratio.

Figure 5

Receptor-ligand recognition on biomimetic particles. Cryo-TEM revealed the PC bilayer surrounding a silica particle. The GM1 receptor inserted in supported PC bilayers recognized its ligand, the cholera toxin. Copyright © 2005 American Chemical Society. Adapted with permission from Mornet S, Lambert O, Duguet E, Brisson A. The formation of supported lipid bilayers on silica nanoparticles revealed by cryoelectron microscopy. Nano Lett. 2005;5:281–285 Abbreviations: TEM, transmission electron microscopy; PC, phosphatidylcholine.