Lipid-based nanoparticle

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). 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. 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. == Synthesis ==

Different formulation procedures include high shear homogenization and ultrasound, solvent emulsification/evaporation, or microemulsion. Obtaining size distributions in the range of 30-180 nm is possible using ultrasonication at the cost of long sonication time. Solvent-emulsification is suitable in preparing small, homogeneously sized lipid nanoparticles dispersions with the advantage of avoiding heat. The obtained LNP formulation can be filled into sterile containers and subjected to final quality control. However, various measures to monitor and evaluate product quality are integrated in every step of LNP manufacturing and include testing of polydispersity, particle size, drug loading efficiency and endotoxin levels. == 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. Drug delivery Solid lipid nanoparticles can function as the basis for oral and parenteral drug delivery systems. SLNs combine the advantages of lipid emulsion and polymeric nanoparticle systems while overcoming the temporal and in vivo stability issues that troubles the conventional as well as polymeric nanoparticles drug delivery approaches. or thiol groups for adhesion via disulfide bond formation can be immobilized on their surface. A recent study has demonstrated the use of solid lipid nanoparticles as a platform for oral delivery of the nutrient mineral iron, by incorporating the hydrophilic molecule ferrous sulfate (FeSO4) in a lipid matrix composed of stearic acid. Carvedilol-loaded solid lipid nanoparticles were prepared using hot-homogenization technique for oral delivery with compritol and poloxamer 188 as the lipid and surfactant, respectively. Many nano-structured systems have been employed for ocular drug delivery. SLNs have been looked at as a potential drug carrier system since the 1990s. SLNs do not show biotoxicity as they are prepared from physiological lipids. SLNs are useful in ocular drug delivery as they can enhance the corneal absorption of drugs and improve the ocular bioavailability of both hydrophilic and lipophilic drugs. SLNs have another advantage of allowing autoclave sterilization, a necessary step towards formulation of ocular preparations. Advantages of SLNs include the use of physiological lipids (which decreases the danger of acute and chronic toxicity), the avoidance of organic solvents, a potential wide application spectrum (dermal, per os, intravenous) and the high pressure homogenization as an established production method. Additionally, improved bioavailability, protection of sensitive drug molecules from the outer environment (e.g. water, light), and even controlled release characteristics were claimed by the incorporation of poorly water-soluble drugs in the solid lipid matrix. Moreover, SLNs can carry both lipophilic and hydrophilic drugs, and are more affordable compared to polymeric/surfactant-based carriers. Nucleic acids A significant obstacle to using LNPs as a delivery vehicle for nucleic acids is that in nature, lipids and nucleic acids both carry a negative electric charge—meaning they do not easily mix with each other. While working at Syntex in the mid-1980s, Philip Felgner pioneered the use of artificially-created cationic lipids (positively-charged lipids) to bind lipids to nucleic acids in order to transfect the latter into cells. However, by the late 1990s, it was known from in vitro experiments that this use of cationic lipids had undesired side effects on cell membranes. During the late 1990s and 2000s, Pieter Cullis, while at the University of British Columbia, developed ionizable cationic lipids which are "positively charged at an acidic pH but neutral in the blood." As of 2021, the current understanding of LNPs formulated with such ionizable cationic lipids is that they enter cells through receptor-mediated endocytosis and end up inside endosomes. In 2018, the FDA approved Alnylam's siRNA drug Onpattro (patisiran), the first drug to use LNPs as the drug delivery system. Several researchers have shown the enhancement of oral bioavailibility of poorly water-soluble drugs when encapsulated in solid lipid nanoparticle. This enhanced bioavailibility is achieved via lymphatic delivery. To elucidate the absorption mechanism, from solid lipid nanoparticle, human excised Caco-2 cell monolayer could be alternative tissue for development of an in-vitro model to be used as a screening tool before animal studies are undertaken. The results obtained in this model suggested that the main absorption mechanism of carvedilol loaded solid lipid nanoparticle could be endocytosis and, more specifically, clathrin-mediated endocytosis. == See also ==