Lipid-based nanoparticles are very small spherical particles composed of lipids. They are a novel pharmaceutical drug delivery system (part of nanoparticle drug delivery), and a novel pharmaceutical formulation. There are many subclasses of lipid-based nanoparticles such as: lipid nanoparticles (LNPs), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs). Sometimes the term "LNP" describes all lipid-based nanoparticles. In specific applications, LNPs describe a specific type of lipid-based nanoparticle, such as the LNPs used for the mRNA vaccine. Using LNPs for drug delivery was first approved in 2018 for the siRNA drug Onpattro. LNPs became more widely known late in 2020, as some COVID-19 vaccines that use RNA vaccine technology coat the fragile mRNA strands with PEGylated lipid nanoparticles as their delivery vehicle (including both the Moderna and the Pfizer–BioNTech COVID-19 vaccines).
Characteristics A lipid nanoparticle is typically spherical with an average diameter between 10 and 1000 nanometers. LNPs are made up of phospholipids, cholesterols, ionizable lipids, and polyethylene glycol-derived lipids (PEGylated lipids). Each of these components play a key role in LNPs used for mRNA vaccines that target SARS-CoV-2 (the virus that causes COVID-19). The ionizable cationic lipids bind to mRNA, PEGylated lipids stabilize LNPs, and phospholipids and cholesterol give LNPs their structure. Because of rapid clearance by the immune system of the positively charged lipid, neutral ionizable amino lipids were developed. A novel squaramide lipid (a partially aromatic four-membered ring that can participate in pi–pi interactions) has been used as part of the delivery system used, for example, by Moderna. Solid lipid nanoparticles (SLNs) possess a solid lipid core matrix that solubilizes lipophilic molecules. Surfactants (emulsifiers) stabilize the lipid core. The emulsifier used depends on administration routes, and is more limited for parenteral administrations. The term "lipid" refers to a broader class of molecules, and includes triglycerides (e.g. tristearin), diglycerides (e.g. glycerol bahenate), monoglycerides (e.g. glycerol monostearate), fatty acids (e.g. stearic acid), steroids (e.g. cholesterol), and waxes (e.g. cetyl palmitate). All classes of emulsifiers (with respect to charge and molecular weight) have been used to stabilize the lipid dispersion. It has been found that the combination of emulsifiers might prevent particle agglomeration more efficiently. An SLN is generally spherical and consists of a solid lipid core stabilized by a surfactant. The core lipids can be fatty acids, acylglycerols, waxes, and mixtures of these surfactants. Biological membrane lipids, such as phospholipids, sphingomyelins, bile salts (sodium taurocholate), and sterols (cholesterol) are used as stabilizers. Biological lipids having minimum carrier cytotoxicity and the solid state of the lipid permit better controlled drug release due to increased mass transfer resistance.
Nanostructured lipid carriers (NLCs) are lipid-based nanoparticles that contain a mixture of solid and liquid lipids in the central core of the lipid carrier. NLCs are derived from SLNs by injecting liquid lipids into the solid core, resulting in a non-uniform internal core. This modification allows for higher drug capacity and more controlled drug delivery.
Preparation Lipid-based nanoparticles are generally prepared by formulation and self-assembly processes rather than by chemical synthesis of the final particle. Common preparation methods include homogenisation, ultrasonication, solvent emulsification and evaporation, microemulsion-based methods, ethanol injection, and controlled mixing of lipid-containing organic phases with aqueous phases. Microfluidic and other continuous-flow mixing methods are widely used for lipid nanoparticle and lipid-based nanomedicine preparation because they allow controlled mixing, continuous production, high-throughput formulation screening and improved control of particle size, polydispersity and reproducibility. In these methods, formulation composition, solvent conditions, lipid concentration, flow-rate ratio, total flow rate, temperature and downstream processing can strongly affect the final nanoparticle population.
Applications Development of solid lipid nanoparticles is one of the emerging fields of lipid nanotechnology (for a review on lipid nanotechnology, see ) with several potential applications in drug delivery, clinical medicine and research, as well as in other disciplines. Due to their unique size-dependent properties, lipid nanoparticles can possibly develop new therapeutics. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could hold great promise for attaining bioavailability enhancement along with controlled and site-specific drug delivery. SLNs are also considered to be well tolerated in general, due to their composition from physiologically similar lipids. The conventional approaches such as use of permeation enhancers, surface modification, prodrug synthesis, complex formation and colloidal lipid carrier-based strategies have been developed for the delivery of drugs to intestinal lymphatics. In addition, polymeric nanoparticles, self-emulsifying delivery systems, liposomes, microemulsions, micellar solutions and recently, solid lipid nanoparticles (SLN) have been exploited as probable possibilities as carriers for oral intestinal lymphatic delivery.
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