Successful Drug Development with Synthetic Lipids: Critical Aspects and Strategies

Currently gaining enhanced momentum due to their vital role in the development of vaccines against COVID-19, lipid-based formulations and lipid nanoparticles have shown a lot of promise in drug development and delivery particularly because of their ability to enhance active pharmaceutical ingredient (API) stability by protecting the API from immune response, proteases and other factors; boost the solubility and bioavailability of drugs with poor water solubility; passively target inflamed or tumor tissues due to their leaky vasculature, known as the enhanced retention and permeation effect; improve the toxicity profile of the entrapped API; targeted drug delivery could improve the toxicity profile of the API further as the APIs are delivered directly to the site of action; deliver difficult APIs such as RNA, which are prone to instability, nuclease-mediated lysis, strong immune responses, and inability to reach the site of action.

In 1995, the U.S. Food and Drug Administration (FDA) approved the first liposomal drug, Doxil®, which encapsulated the cytotoxic drug doxorubicin. Since then liposome drug development continues to trend upward due to advances in liposome and lipid nanoparticle production technologies.

Today, there are 18 liposomal drugs on the market and hundreds of liposomal drugs in clinical trials for a wider range of ailments. There is active work in developing generics of off-patent liposomal drugs and the U.S. Food and Drug Administration (FDA) has issued product-specific guidances for several generic versions of liposomal products. The latest trend in lipid-based drug delivery research and drug development is in the field of nucleic acid delivery, for APIs such as short RNAs for gene silencing or activation (siRNA, miRNA, saRNA) and long RNA (mRNA) for applications in cancer therapy, enzyme replacement therapy, vaccines, and more.