NovoArc – Lipids for Innovation

Dr. David Wurm, Dr. Julian Quehenberger and Prof. Dr. Oliver Spadiut, NovoArc GmbH, Fillgradergasse 7/5, 1060 Vienna, Austria

NovoArc’s Tetraetherlipids

NovoArc uses an extremophilic archaeon for the production of their lipids. Those organisms live under very harsh conditions – low pH values and high temperatures. As a consequence, the lipids in their cell membrane exhibit unique properties which are useful for the delivery of different active pharmaceutical ingredients (APIs) in the pharmaceutical industry. As the lipids contain ether bonds - and not ester bonds like in conventional phospholipids - they are very stable against oxidation, extreme pH ranges (pH 1.0 – 10.0), high temperatures (> 140 °C), and also against the environment in the gastrointestinal (GI) tract such as enzymes and bile salts.

A continuous biotechnological production process

NovoArc employs a continuous biotechnological process for the production of their lipids. This process is defined, controllable, reproducible, and scalable. It was developed according to Quality by Design guidelines and is also patented.

Application potential of NovoArc’s Tetraether Lipids

There are numerous applications for NovoArc’s tetraether lipids (TELs) (Figure 1A), but currently NovoArc focuses on their application in the pharmaceutical industry. The two main application fields are the oral delivery of small molecules and proteins in liposomes (Figure 1B) and the delivery of nucleic acids via lipid nanoparticles (Figure 1C). NovoArc currently offers two different products: A lipid mixture and a pure lipid fraction.

Fig. 1: NovoArc’s tetraether lipids (A) can be used for the delivery of different APIs in liposomes (B) and lipid nanoparticles (C).

Oral drug delivery

Due to the low stability of conventional liposomes, they can only be applied for parenteral (non-oral) purposes. The major benefits of NovoArc’s liposomes are (Figure 2):

  1. the protection of the drug from degradation in the stomach,
  2. stable long term formulation and thus increased shelf life at room temperature and
  3. increased bioavailability of the drug after oral administration.

Fig. 2: NovoArc’s liposomes allow the oral delivery of numerous APIs. The API is protected in the stomach from degradation and the bioavailability is significantly improved.

To show the improved storage stability of APIs using NovoArc’s liposomes, we encapsulated the model compound Cannabidiol (CBD), which is sensitive to oxidation and to light. After storage at room temperature under the exposure of light we could demonstrate a significantly higher active CBD content by NovoArc’s liposomes compared to conventional liposomes (Figure 3A). We also tested the protection of encapsulated CBD in the simulated GI tract and found 20% less degradation compared to conventional liposomes (Figure 3B).

Fig. 3: NovoArc’s liposomes protect their cargo during storage and in the gastrointestinal tract. (A) Encapsulted Canabidiol (CBD) stored at room temperature under light exposure. (B) Encapsulated CBD is analyzed in a simulated gastrointestinal tract.

Parenteral delivery of RNA and DNA

NovoArc lipids were also tested for the delivery of mRNA with lipid nanoparticles (LNPs). The uptake as well as the transfection efficiency of LNPs incorporating tetraether lipids (TELs) were compared to conventional LNP formulations. In vitro studies on three different cells lines were conducted: human skeletal myoblasts (HSkM), cancerous murine myoblast cell line (C2C12) and epithelial colon cell line (Caco2). Cells were transfected with mRNA coding for green fluorescent protein (GFP). NovoArc’s formulation was able to boost the transfection efficiency significantly (Figure 4). In Caco 2 cells, the transfection efficiency was even increased by the factor 11.

Fig. 4: NovoArc’s LNPs were tested for transfection using mRNA encoding GFP, (A) Comparison of transfection efficiency of conventional LNPs and NovoArc’s LNPs on human skeletal myoblasts (HSkM), cancerous murine myoblast cell line (C2C12), and epithelial colon cell line (Caco2). (B) exemplary microscopy pictures of transfected Caco 2 cells.

NovoArc’s future perspectives

NovoArc is a research driven deep tech Spin-off that continuously strives for innovation and novel products. We are currently conducting in vivo studies to further prove the benefit of our lipids and in a few weeks, we will launch a new lipid class as commercial product.

Contact us if you want to support us in enabling improved medical care by manufacturing unique lipids for next generation drug formulation.