After more than 25 years of commercial use with almost 20 parenteral drug products, lipid nanoparticles (LNPs) are having a breakout moment. While LNPs are now a proven drug delivery technology to penetrate target cells and ensure release for reliable systematic or local delivery, their true market potential as a gene and cell therapy enabler has only become clear to many since COVID-19.

More than ten of the COVID-19 vaccine candidates in development around the world, including many clinical front-runners, are utilizing LNPs for mRNA, DNA or peptide delivery according to the latest WHO list. If favorable clinical data continues to be generated at the current rate, it is probable that hundreds of millions of vaccine doses made with LNP-technologies will be manufactured for human use over the coming year.

There are several reasons why LNPs are now increasingly recognized as a preferred formulation technology for specialized parenteral drug products, explains Jay Natarajan, who is Director of R&D at Evonik’s CDMO center for LNPs and other nanomedicines located in Vancouver, Canada.

“LNPs have attained a long history of safety in encapsulating genetic material including mRNA, as well as a range of other biologically active agents, for controlled delivery to a target cell or organ site. When it comes to the protection of a payload against degradation while enhancing biodistribution and solubility, LNPs are now considered by many to be a best-in-class technology,” said Dr. Natarajan.

In addition to being safe and efficacious, they are also simple to customize and efficient to manufacture to help accelerate clinical timelines and reduce project cost. For these and other reasons, LNPs have helped to herald the arrival of a new era of medicine where genetic diseases can be effectively treated or cured, or where vaccines can be produced within the body rather than by the purification of non-infectious viruses.

“Virtually any biologically active agent has the potential to be formulated with lipid nanoparticles including hydrophobic drugs, small molecules, proteins and peptides, oligonucleotides and mRNA,” said Dr. Natarajan.

Significant opportunities exist for LNP-based formulations to create drug products for protein replacement therapy, for preventative or curative vaccines, and for gene editing purposes. In addition to RNA, DNA and siRNA-based therapeutics, LNP-based formulations are also being increasingly considered for use across a variety of other application areas including anti-cancer agents and antibiotics, peptide and protein-based synthetic vaccines, ligand-targeted formulations and imaging contrast agents.

“Over the coming decade, LNPs are also expected to enable the development of even more complex nanomedicines,” said Dr. Natarajan. Examples include the development of drug combination products, synthetic vaccines or immunotherapies where LNP-based formulations are required to ensure the co-presentation of multiple components into the target cell. Additional opportunities include combining LNPs with tissue sequencing and other functional technologies to help create personalized or custom-made formulations that can enable outcomes such as the insertion of tumor-associated neo-antigens into mRNA vaccines.

“Given the highly specialized nature of developing LNP-based drug products, it is common for pharmaceutical companies to partner with CDMOs that have established core competencies and a proven record for performance within this technology area. Such strategic partnerships may not only span formulation and process development activities, but also the clinical and commercial manufacturing of the finished drug product,” said Dr. Natarajan.

Evonik is one of the world’s leading CDMOs for LNP-based drug products. The global leader for advanced drug delivery has more than 25 years of industry leadership in this space through its acquisition and integration of the Canadian CDMO Transferra Nanosciences (previously Northern Lipids). Approximately 50% of all LNP-based drug products approved to-date have received the support of either Evonik or Transferra.

Hundreds of LNP-based formulations for gene and cell-based therapies as well as other nanomedicines with a broad, global base of pharmaceutical and biotech companies. A range of CDMO services are available to support customer projects from drug discovery and pre-clinical studies through to the large-scale GMP production and aseptic filling of the final drug product. Its LIPEX® platform of extruders has also set the standard for liposome manufacturing for more than two decades. If you are looking for a CDMO partner to review the feasibility or develop a drug product in an LNP-based formulation, contact the team at Evonik via healthcare@evonik.com.