Lipid-based vehicles are one of the most commonly used methods for delivering poorly water-soluble drugs. They can fall into one of four classes: liposomes, lipid nanoemulsions (LNEs), lipid nanoparticles (LNPs), or Solid Lipid Nanoparticles (SLNs)/Nanostructured Lipid Carriers (NLC).
These vehicles contain one to two layers of water-soluble lipids which also orient as a sphere to coat drugs. Due to their minimal adverse side effects, lipid-based drug delivery is universally used to safely transport drugs within the body. However, some drawbacks exist, including premature drug release, instability, low biodegradability, and cellular toxicity.
While liposome technology has seen use since the 1960s, the development of lipid nanoparticles has been more recent. Lipid nanoparticles for drug delivery have seen recent success as the carrier for COVID-19 mRNA used in the novel vaccine.
Despite the success and overall efficacy of lipid-based nanoparticles for drug delivery, we at Phoreus Biotech have improved upon this industry-standard carrier by developing our BAPC®️ and CAPC peptide-based carrier technology, which combats premature drug release, instability, low biodegradability, and cellular toxicity.
The Role of Lipid Nanoparticles as Drug Carriers
Lipids nanoparticles are tiny lipid particles that transport drugs throughout the body. Lipid nanoparticles, a newer drug delivery innovation based on liposome technology, have shown to be highly effective at transporting compounds throughout the body.
Lipid nanoparticles for drug delivery are effective at transporting compounds throughout the body due to their size and adaptable surface characteristics. Lipid nanoparticles’ qualities, such as size and composition, can be seamlessly engineered to better suit a drug’s specific delivery needs and optimize performance.
Nanoparticles pose less cytotoxicity than liposomes, are readily manufacturable, and are highly compatible with cellular environments. The nanoparticles can also be engineered to directly treat diseased cells within a specific region of the body. Nanocarriers can be designed to avoid triggering the body’s immune response, thus ensuring the drug’s safe delivery.
Lipid nanoparticles still have problems, such as low drug loading efficacy and potential for drug crystallization while in storage. Lipid-based carrier toxicity can result from disruption of membrane function and integrity and bio-accumulation. Both can lead to cell death, which we at Phoreus have worked to overcome in developing our BAPC®️ and CAPC technology.
How Do Lipid Nanoparticles Work?
Lipid nanoparticles are spherical aggregated lipids coated by an additional single layer of lipids. The lipid nanoparticle delivery system works to coat an API for delivery throughout the body. A surfactant stabilizes the interior lipid core into which the API is integrated. As the nanoparticle and API travel throughout the body, the stability of the nanoparticle remains intact before the targeted cellular region receives it.
Due to their cellular membrane-like nature, lipid nanoparticles can mimic membrane qualities for easy binding and release into cellular regions. Lipid nanoparticles can also be developed using ligand-receptor communication for cellular targeting so that an API is delivered to a specific region of the body. By ensuring the stability of the lipid nanoparticle, the risk of drug toxicity is reduced as the drug delivery is concentrated at the affected site rather than elsewhere in the body.
Lipid Nanoparticle Manufacturing
Considering how lipid nanoparticles for drug delivery are a relatively new technology, there has yet to be a universally acceptedmethod for their manufacturing. While most lab-scale techniques cannot yield large-scale quantities of lipid nanoparticle drug emulsions, only a few large-scale methods exist.
There are two main methods for lipid nanoparticle manufacturing: low and high energy. Methods employing low-energy techniques, such as solvent diffusion, could be better, as removing solvents is tedious and can contaminate the target emulsion. High-pressure homogenization is a preferred high-energy method for manufacturing the lipid nanoparticle and API emulsion due to the variety in equipment availability and the possibility of developing it into a large-scale technique.
Types of Lipid-Based Nanoparticles
Lipid-Based Nanoparticles are all spherical aggregations of lipids. Depending on their specific structure, lipid-based nanoparticles fall into one of four classes: liposomes, lipid nanoemulsions (LNEs), lipid nanoparticles (LNPs), or Solid Lipid Nanoparticles (SLNs), and Nanostructured Lipid Carriers (NLC).
Liposomes contain two layers of water-soluble lipids that encapsulate an aqueous interior region. They are created from naturally occurring phospholipids and cholesterol and are commonly used in injectables. The surface of liposomes can be coated with proteins to target a specific cell within the body and deliver multiple drugs at once. Liposomes can also transport hydrophobic and hydrophilic drugs due to their phospholipid bilayer structure. While liposomes are some of the earliest and simple lipid-based delivery vehicles, they still succeeded in drug delivery as they evade the body’s immune system and retain stability until they reach a target area.
Despite the successes of liposomes, there is still a major risk of cellular toxicity due to the membrane-like nature of liposomes. At Phoreus, we have built a better peptide-based nanocarrier that still interacts seamlessly with cellular membranes without posing harmful interference with its function and integrity.
Lipid Nanoparticles (LNPs)
Lipid nanoparticles are closely related to liposomes and are often confused with one another. Lipid nanoparticles are newly developed, reaching prominence after their breakthrough use in the novel COVID-19 vaccines. Compared to Liposomes, lipid nanoparticles specialize in delivering oligonucleotides instead of delivering APIs. The risk of cellular toxicity is lower as LNPs do not incorporate a phospholipid bilayer structure, as seen in liposomes. Instead, lipid nanoparticles host a single phospholipid layer that coats lipid micelles. Within the lipid micelles is where DNA and RNA fragments are loaded.
While lipid nanoparticle delivery systems have been developed from liposome technology, they have improved upon the drawbacks of liposomes. Increased stability and lessened cytotoxicity are significant advancements in lipid nanoparticle delivery systems. Nevertheless, lipid nanoparticles have demonstrated setbacks such as lessened drug loading efficacy. At Phoreus, we have worked around the disadvantages of the industry standard lipid-based carriers by developing our BAPC®️ and CAPC peptide-based carrier technology. Our peptide-based carriers pose virtually no cytotoxicity while retaining stability and high-drug loading efficacy.
Lipid Nanoemulsions (LNEs)
Lipid nanoemulsions include a single layer of lipids that encapsulates an inner region of lipid droplets where an API is loaded. LNEs are mainly plant-based lipid droplets that are stabilized by phospholipid coatings. They do not see much use as drug carriers but are most commonly used to administer nutrition intravenously.
Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs)
Compared to the other three classes of lipid-based nanoparticles, SLNs, and NLCs are solid nanocarriers at room temperature. Both include a single layer of phospholipids incorporating an interior region of rigid lipids into which an API is loaded. Due to setbacks in drug delivery and loading efficacy, NLCs were developed. NLCs include areas of liquid lipids alongside rigid lipids within the nanocarrier interior and have seen increased effectiveness.