Technology Platforms
Biotransport™ technology
Biotransport™ is an innovative technology that creates novel anticancer drugs by combining proven active pharmaceutical ingredients (API) with proprietary compounds selected from Supratek’s libraries of amphiphilic polymers and modified cyclodextrins.
CombiForm™ is a new toolbox based on computational and combinatorial chemistry principles that generates libraries of proprietary compounds to help design drug compositions with improved pharmaceutical properties, including bioavailability, pharmacokinetics, distribution and metabolism.
Biotransport™ carrier technology has two principal platforms: BioMod™ and BioTrans™ that enable and enhance therapeutic performance of API without changing their chemical structures. BioMod™, BioTrans™ and CombiForm” have been validated with a number of approved APIs including taxanes, anthracyclines, camptothecins and podophylotoxins. Supratek product pipeline is illustrative of the successes obtained using these technologies and platforms both in pre-clinical and clinical development.
The enabling components used in BioMod™ platform technology are nonionic amphiphilic polymers. The formation of amphiphilic nanocomplexes plays several major enabling and enhancing roles in drug design:
- Bilological response modification
Certain polymers have the ability to selectively enable cytotoxic activity of API against
chemoresistant cancer cells, including cancer stem cells that are believed to be the major factors
promoting cancer progression.
Supratek discovered that BioMod™ polymers have an ability to selectively disrupt mitochondrial functionality in chemoresistant cells . They penetrate cancer cells; reach mitochondrial membranes; compromise their function by depleting ATP; and release ROS and cytochrome C. The depletion of ATP inactivates the detoxification mechanisms by inhibiting ABC transporters such as P-gp and MRP. The release of ROS and cytochrome C sends an apoptotic signal.
Biological response modifying polymers are safe to normal cells but are highly specific to cancer cells and make MDR cells vulnerable and sensitive to cytotoxics. Enabling the penetration of cytotoxics into MDR cancer cells by the inactivation of the detoxification mechanisms creates a therapeutic opportunity. The combination of a BioMod™ polymers with an anticancer API results in a new drug that targets chemoresistant cancers.
BioMod™ platform has successfully produced SP1049C, SP1012C and SP1015C, three novel chemotherapeutic drugs in our pipeline.
Supratek discovered that BioMod™ polymers have an ability to selectively disrupt mitochondrial functionality in chemoresistant cells . They penetrate cancer cells; reach mitochondrial membranes; compromise their function by depleting ATP; and release ROS and cytochrome C. The depletion of ATP inactivates the detoxification mechanisms by inhibiting ABC transporters such as P-gp and MRP. The release of ROS and cytochrome C sends an apoptotic signal.
Biological response modifying polymers are safe to normal cells but are highly specific to cancer cells and make MDR cells vulnerable and sensitive to cytotoxics. Enabling the penetration of cytotoxics into MDR cancer cells by the inactivation of the detoxification mechanisms creates a therapeutic opportunity. The combination of a BioMod™ polymers with an anticancer API results in a new drug that targets chemoresistant cancers.
BioMod™ platform has successfully produced SP1049C, SP1012C and SP1015C, three novel chemotherapeutic drugs in our pipeline.
BioMod™ polymers additional features:
- Enabling CNS and oral delivery of API
As with chemoresistant cancer cells, the ABC transporter mediated efflux mechanisms control the
function of natural epithelial and endothelial barriers, such as gastrointestinal and blood-brain
barrier, thus making them impermeable to many drugs.
Transient inactivation of ABC transporters of these barriers by absorption enhancers, opens new therapeutic opportunities such as the delivery of drugs to the central nervous system and the oral administration of chemotherapeutic drugs. Supratek’s first oral chemotherapeutic is SP1060C-O, an oral topotecan.
Transient inactivation of ABC transporters of these barriers by absorption enhancers, opens new therapeutic opportunities such as the delivery of drugs to the central nervous system and the oral administration of chemotherapeutic drugs. Supratek’s first oral chemotherapeutic is SP1060C-O, an oral topotecan.
- Solubilisation
Nanoparticles formed by amphiphilic polymers can serve as vehicles for the solubilisation and
transport of API. The size of these particles range from 10 to 100 nm, which is suitable for
intravenous and oral administration routes. The BioMod™ -dissolved API molecules are released after
the administration of the drug to the patient.
BioTrans™ platform uses cyclic carbohydrates such as surface modified cyclodextrins as carriers of API.
Cyclodextrins are natural amphiphilic compounds, These molecules have a hydrophilic external surface that is water compatible, makeing them easily soluble. Their internal cavity however, is hydrophobic and can accommodate an insoluble API molecule on a “host-guest” principle. The API loaded into the cavity is sheltered from the environment, which enables its administration and improves its pharmacokinetics and metabolism. The retention and release of the drug molecule inside the cavity can be regulated by modifications to the surface of the carrier.
API loaded into BioTrans™-modified cyclodextrin and secondary carrier components, hold, stabilize and shelter the API until its delivery to the critical disease site. Thereby enhancing therapeutic performance of the API.
Two of Supratek drug candidates are based on this platform: SP1031C and SP1063C. The following figure illustrates the structural organization of SP1031C, which is typical for BioTrans™ type of nanomedicines.
