SR Pharma claims formulation triumph in siRNA drugs
in the formulation of siRNA drugs, enabling them to be stored at
room temperature and reconstituted in one simple step, thus
extending shelf life and making administration easier.
Up to now, siRNA drugs and their liposomal components have needed to be separately lyophilised (freeze-dried), reconstituted and then combined in a multi-step painstaking process.
The new SR Pharma process on the other hand allows siRNA drugs pre-formulated as liposomal nanoparticles to be freeze-dried and then simply reconstituted with water immediately prior to intravenous infusion to patient with no additional preparation steps such as sonication required.
This lyophylised dry powder drug formulation needs no cooling chain to follow from the manufacturer to the clinic, making it easy to ship and store.
SR Pharma's drugs are based on RNA interference (RNAi), a natural selective process for turning off genes, which holds great potential in its ability to treat disease at the genetic level.
In contrast to other classes of therapeutics such as proteins, antibodies and small molecules, RNAi requires neither "drugable" domains on the molecular target (e.g. kinase domains) nor specific locations at the cell membrane or extra-cellular.
RNAi is triggered by siRNA (short interfering RNA) molecules that engage a group of cellular proteins, known as RISC (RNA induced silencing complex).
RISC guides the siRNA to its target mRNA (messenger RNA) by complementary base pairing and breaks it up in a selective fashion, thus halting protein expression or viral replication.
To achieve systemic delivery of siRNA, SR Pharma has developed a liposomal delivery system, called AtuPLEX, which consists of a cationic lipid, that introduces the therapeutic siRNA molecule into mammalian cells, and a fusiogenic lipid that allows the escape of the siRNA from the endosomal/lysomal compartment inside the cytoplasm of the cells.
"Although lyophilisation in an extra step in the production it may even lower the overall costs," Klaus Giese, SR Pharma's chief scientific officer, told In-PharmaTechnologist.com.
"The conventional method would be a liquid solution which would need storage in bottles, since glass is required to prevent interaction of the lipid components with specific plastics, but transportation of glass bottles requires careful handling."
The dry powder procedure has been advanced from bench scale to a 150ml formulation and Giese said the next steps are to lyophilise the envisioned final product which will be in the range of 2l-5l.
The commercialisation aspects will be looked at after completion of the preclinical toxicology data, he stressed.
Nevertheless, SR Pharma uses its liposomal technologies not only for its cancer drugs, currently in preclinical development, but also for collaborations with other pharmaceutical firms such as sanofi-aventis and Quark Biotech.
Clinical development of the company's therapeutic molecules for systemic applications in oncology programmes are targeted to start in 2007, while therapeutic programmes for its collaborators are scheduled to commence clinical trails in the second half of 2006.
