Lipid nanoparticles (LNPs) are a new platform for delivering poorly soluble drugs and nucleic acids. They have entered the clinic through mRNA-based vaccines such as the approved mRNA-1273 and BNT162b COVID-19 vaccines. Lipid nanoparticles are multicomponent lipid systems, typically composed of phospholipids, ignitable lipids, cholesterol and PEGylated lipids .
They can be formulated into liposomes, noisome, transferases, solid lipid nanoparticles (SLNs), or nanostructured lipid carriers (NLCs). They are stable at physiological pH and deliver a payload into target cells by the invagination of their membranes.
1. Targeted Delivery
In a typical medication administration, the drug is absorbed from the gastrointestinal tract or directly injected into the bloodstream and is distributed throughout the entire body. However, only a small percentage of the medication can reach the organ that needs treatment.
Targeted delivery involves modifying the properties of a drug to increase its concentration in diseased tissues relative to healthy tissue. This can be accomplished by encapsulating drugs in nanoparticles designed to avoid removing these medications through body mechanisms like metabolism, excretion, opsonization, and phagocytosis.
This can be done through passive targeting, which involves using the properties of the drug carrier to escape body defenses, or active targeting, which is achieved through specific modifications to the drugs that are loaded into the drug carriers.
Passive targeting involves a combination of factors, including ensuring that the drug carriers do not interact with normal tissues and have properties that allow them to escape the blood vessel walls through leaky or damaged cell membranes.
For example, Ge et al. used fluorinated polymers to create drug carriers that can penetrate airway mucus, and they found that siRNA delivered through these drug carriers reduced the pro-inflammatory response in the lungs following acute lung injury.
2. Reduced Leakage
Lipid nanoparticle formulation are a promising drug delivery system that can deliver nucleic acids, proteins and other poorly soluble drugs. They are stable, reversible and do not elicit a harmful immune response in humans.
LNPs are a versatile formulation platform that can be modified with various lipids, surfactants, and payloads.
They are produced by multiple methods, including solvent diffusion and high shear homogenization (HPH). Using solvent injection or diffusion, SLNs combine solid lipids with an aqueous surfactant solution. Emulsifiers stabilize them to form a spherical particle with a single phospholipid layer and optionally embedded with other payloads.
RNA-encapsulated LNPs have been used to develop vaccines for various indications, most recently in the COVID-19 vaccine (Nonpatrol). They can also be used to treat a variety of cancers, including hepatocellular carcinoma, multiple myeloma and leukemia.
They offer better encapsulation efficiency than transferases and are more stable than liposomes. They also have a lower zeta potential, which makes them less prone to drug leakage.
3. Improved Bioavailability
Lipid nanoparticles are an efficient drug delivery system that can deliver nucleic acids, RNA, poorly soluble drugs and other APIs to cells. They are used in vaccine development (most recently, the COVID-19 RNA vaccine Nonpatrol), different cancer therapeutics, and gene therapy for genetic diseases such as hemophilia A & B.
The physicochemical properties of LNPs significantly impact there in vivo efficacy. Optimizing the relative amounts of ignitable lipid, helper lipid and cholesterol, as well as the size and surface charge of the lipid bilayer, is key to improving cell uptake. Once inside cells, lipids can self-assemble to release the encapsulated payload.
This is a crucial step in the success of lipid-based pharmaceuticals and needs to be tailored for each application and administration route. Choosing a CMO or CDMO that has the right expertise and equipment to perform a robust formulation process is essential. Lipid nanoparticles must be kept stable and sterile, so they must be manufactured using closed systems and under strict temperature control.
In addition, it is important to perform sterile filling and liquating in compliance with current good manufacturing practices (camp’s). The team at Precision Nano Systems has the experience and equipment to bring your lipid-based pharmaceutical to market.
4. Reduced Inflammation
Once thought to be the body’s natural healing response, inflammation is now recognized as a major cause of many chronic diseases such as cancer, autoimmune diseases, heart disease and diabetes. This is because inflammation can lead to poor circulation, causing oxidative stress that damages cells and leads to aging.
Lipid Nanoparticles encapsulate nucleic acids and a drug or targeting molecule targeted to a specific cell population. They are then transported into cells via an endogenous cellular transport pathway. Once encapsulated in the endosomal compartment, the ignitable lipids react with an acidic pH to release their cargo into the cytoplasm.
These particles are a highly versatile and cost-effective carrier for delivering a wide range of therapeutics, including mordant, siRNA and mRNA, as well as drugs and vaccines. The resumption of clinical trials and new product launches fueled demand for lipid nanoparticles in 2021.
5. Improved Immune Response
Lipid nanoparticles (LNPs) are clinically advanced nucleic acid delivery systems that have become a promising vector for several therapeutic options in the pharmaceutical industry. They are most commonly used to deliver nucleic acids but could also be adapted to carry small molecules and peptides.
LNPs have been a key driver behind the recent boom in new RNA-based vaccines and personalized medicines, which are being developed for various diseases, such as cancer, HIV, and flu. Specifically, Modern and Biotech/Pfizer developed mRNA vaccines that have been accelerated to clinical development using LNPs.
A typical LNP formulation is a multi-component system that includes phospholipids, an ignitable lipid, cholesterol and a PEGylated lipid. The lipid bilayer produces spherical structures that the cells can use through endocytosis, fusing with vesicles and releasing their cargo.
They can also be formulated to include pH-sensitive lipids, enabling the encapsulated nucleic acid to be removed from the blister at a predetermined time after injection. This allows nucleic acid delivery to specific cellular sites and prevents it from entering cells at non-specific locations.