Many promising drug candidates fail to reach the market mainly due to poor water solubility, low bioavailability, and potential toxicity; additionally, the current drug discovery process is costly and inefficient. Formulation development represents an important strategy to maximize the success of drug discovery by ensuring high solubility and bioavailability and reduced toxicity. While there have been incremental successes in the field, most of the drug carrier materials in lipid-based or polymeric drug delivery systems use inert substances that lack therapeutic effects, and the use of excess carrier materials adds to the cost and poses potential safety issues. A dual-functional carrier system could enhance the therapeutic benefits of the drug while limiting cost and undesirable side effects.
Description
A novel drug formulation based on PEGylated FTS, a synthetic farnesylcysteine mimetic, acts as a potent and particularly non-toxic antagonist of the Ras family proto-oncogenes present in one-third of human cancers. FTS inhibits the growth of Ras-dependent tumors with no significant toxicity; in addition to its antitumor activity in mice and humans, FTS also exhibits anti-inflammatory activity. PEGylation serves to improve the solubility of FTS, which has a hydrophobic nature and limited bioavailability. The PEG-FTS conjugate forms small-sized micelles, a type of delivery system that has gained considerable attention due to micelles’ small size and ability to solubilize water-insoluble anticancer drugs and accumulate specifically at tumor sites. In this new formulation, both the anticancer drug and the PEG-FTS carrier display antitumor activity and can synergize to amplify the effect. Further, the drug-loading capacity and formulaic stability of the PEG-FTS micellar system can be further improved via incorporation of a drug-interaction motif, leading to the creation and development of highly effective therapeutics with minimal toxicity at a low cost in a timely manner.
Applications
• Dual-function drug delivery platform
Advantages
• Improved stability and loading capacity
• Synergistic effects from anticancer properties of both drug and carrier
• Simpler path to development with a lower associated cost
Invention Readiness
In vivo data
IP Status
https://patents.google.com/patent/US9855341B2; https://patents.google.com/patent/US10376591B2
