Conventional lipids, like phospholipids, are sensitive to the harsh environment of the gastrointestinal tract and can therefore not protect and deliver desired drug substances. As a result, conventional liposome and lipid nanoparticles are applied via a parenteral route. The key advantages of NovoArc´s lipids and lipid formulations containing these are:
- Protection against gastrointestinal hydrolysis, enzymatic lipolysis, and agglomeration
- Extended shelf life at room temperature
- Enhanced bioavailability after oral administration.
Therefore, NovoArc lipids can be used to deliver multiple drug substances to the intestine and have been tested in animal studies, showing high tolerability after oral administration.
Small molecules
The encapsulation of small molecules into liposomes allows for controlled and prolonged release in the body. Liposomes can enhance the solubility of hydrophobic drugs, increasing their bioavailability and therapeutic effectiveness. Additionally, liposome encapsulation helps to reduce toxicity and target specific tissues or cells, minimizing side effects.
- Case study Cannabidiol
Tetraether lipids are advantageous for CBD encapsulation, because they offer enhanced chemical, physical, and physiological stability compared to conventional liposomes, protecting CBD from degradation (Figure A and B). They improve bioavailability by increasing the uptake in the GI tract up to six times and reducing the need for high CBD doses (Figure C and D). Additionally, tetraether lipids show superior storage stability, resisting oxidation and hydrolysis, and offer lower dependency on food intake, which enhances patient adherence.
Peptides and Proteins
Encapsulating peptides and proteins into liposomes, containing tetraether lipids, protects them from enzymatic degradation, enhancing their stability and prolonging their half-life in the gastrointestinal tract. Liposomes also improve the delivery of these biomolecules by facilitating their uptake into target cells and tissues. Moreover, liposome encapsulation can reduce immune responses and adverse reactions, ensuring safer and more effective therapeutic outcomes.
- Case study Insulin
The protein Insulin is currently used only subcutaneous and for each treatment a needle sting is needed. The encapsulation into highly stable particles can enable the oral application of insulin and therefore increase the patient compliance dramatically. NovoArc´s lipids showed in the following publication that insulin can be successfully encapsulated and is therefore protected from gastric fluids.
Figure: Cryo-TEM of lyophilized insulin containing liposomes
- Case study Vancomycin
Vancomycin is a glycopeptide and is used as a last stage antibiotic. Because of its low oral bioavailability, the drug only applied parenteral. However, the antibiotic is highly potent and can be used for many multi-resistant microbials. By the encapsulation into tetraether lipid containing liposomes we were able to show an increased oral bioavailability by nearly 9 times, shown in the diagram below. (Publication in preparation)
In an assay simulating the environment of GI tract, 20% less degradation of NovoArc’s encapsulated CBD, compared to conventional liposomes was found.
Figure: Vancomycin concentration in blood samples after oral administration.
Nucleotides
In the past years nucleotides like mRNA and microRNA have been researched and used intensively. In order to achieve therapeutic relevance, the nucleotides need to be encapsulated into lipid nanoparticles, which protects them from enzymatic degradation until they are taken up by a cell. The currently used lipid formulations are designed and used for the intra muscular application but are not suitable for oral application. The addition of NovoArc´s tetraether lipid can help to create more stable and resistant particle which can lead to improved oral bioavailability.
- Case study mRNA
The by NovoArc produced native TELs (archea lipid extract) and the GDGT (tetraether lipid) were researched within a commercial LNP formulation and increased the particle uptake and transfection in Caco-2 cells significantly (Figure below). Our Data shows the beneficial effects of the tetraether lipids in LNP formulation and demonstrates the opportunity of oral administration.
Figure: Increase particle uptake and increased expression of GDGT and TEL containing LNPs in Caco-2 cells.