**Abstract**

Nanostructured materials require evaluation at a molecular level to become controllable and useful in drug and vaccine delivery. Over the years self-assembled nanomaterials such as nanoparticles and thin films have been prepared, characterized and used for biomedical applications. In this review meaningful examples of biomimetic nanomaterials and their construction based on intermolecular interactions such as the electrostatic attraction or the hydrophobic effect will be discussed. Emphasis will be placed on the interactions between polymers, lipids, surfactants and surfaces leading to bioactive supramolecular assemblies such as nanoparticles and coatings. Among the important applications of the self-assembled nanostructures and films to be reviewed are their antimicrobial effect and their adjuvant activity for vaccine delivery.

**Keywords:** lipid polymer nanoparticles, antimicrobial nanostructures, adjuvants for vaccines, intermolecular interactions, assembly and disassembly

### **1. Introduction**

Life is ephemeral as are the assemblies that make life possible. Among the nanomaterials, the biomimetic nanomaterials mimic the assemblies found in living creatures and may find a myriad of useful applications [1–9]. The bioactive biomimetic nanomaterials encompass a wide variety of hybrid metastable nanostructures keeping different or similar molecules transiently together thanks to weak but frequent intermolecular interactions as are the van der Waals, the hydrogen bridges, the electrostatic and electrodynamic interactions, and the hydrophobic effect [10, 11]. Among these, one may say that the lipid polymer, the lipid inorganic materials and the coatings with NPs inclusion have been the subject of important developments in drug and vaccine delivery to fight pathogens and prevent, treat or diagnose major human diseases such as cancer. Stimuli responsive assemblies with the use of various triggers such as pH, temperature, light, enzyme, and redox potential are emerging strategies for the effective localization of the bioactives at the tumor site for safe and effective cancer therapy or diagnosis despite all problems with multidrug resistance, long-lasting chemotherapy and low transfection and non-specific immuneresponse after systemic delivery of siRNa [12]. For example, a biomimetic phospholipid-like amphiphilic prodrug, 1-O-octodecyl-2-conjugated linoleoyl-sn-glycero-3-phosphatidyl gemcitabine (OLGPG) combined with cholesteryl hemisuccinate polyethylene glycol 1500 (CHS-PEG) upon injection in water

formed the OLGPG and OLGPG/CHS-PEG nanometric spherical vesicles due to the hydrophobic interaction of lipid moieties. Since phospholipase A2 (PLA2) is highly expressed in tumor tissues and specifically degrades the 2-acyl of the phospholipids to lysophospholipids, a PLA2-sensitive OLGPG specific degradation in the tumor tissue was obtained [13]. In this same work, the in vivo experiments with a hepatocellular tumor-bearing mouse model showed that these long-circulating phospholipid-like prodrug nanoassemblies yielded the highest antitumor and tumor targeting effects compared to the other groups [13].

Today (30 November 2018) a search of the literature on lipid polymer coatings in the Scopus database produced 26,123 items whereas a search on lipid polymer nanoparticles resulted in 24,042 publications. I feel somewhat proud to have witnessed and contributed to some of the early and late developments on lipid polymer [14–23] and lipid silica NPs [24–29] that started about 3 decades ago. In particular, cationic lipids by themselves or in combination with other lipids or assemblies can yield interesting microenvironments to accommodate a variety of bioactive molecules such as drugs, antigens, peptides, nucleic acids, etc. [30–37]. The nanometric size and positive charge impart desirable properties for the cationic assemblies after injection via parenteral route in vivo. Good instances are the direct action at the lymph nodes for stimulation of dendritic cells for vaccines [9, 22, 31, 34–37], and the penetration of nasal mucosae to overcome the blood brain barrier releasing drugs into the brain [33]. Other important applications relate to the antimicrobial properties of a variety of cationic assemblies either by themselves such as cationic bilayers or in effective combinations with other antimicrobials such as antibiotics, polymers or peptides [7, 23, 38–45].

This review will discuss mostly seminal and recent contributions regarding applications of biomimetic nanoparticles and coatings in antimicrobial therapy and vaccine development. Emphasis will be placed on lipid polymer NPs and their coatings plus their biomedical applications in drug and vaccine delivery.
