LiPlasomes to transport drugs

The drug loaded lipid nanocarriers are designed to be particularly susceptible to degradation by phospholipase A2 (PLA2), which is upregulated in the tumor microenvironment of several cancer types.

The targeted drug delivery principle consists of long circulating nanoparticles such as liposomes or micelles that accumulate in porous cancer tissue with a high PLA2 activity. The carrier nanoparticles are composed of special prodrug lipids whose degradation products, after exposure to PLA2, are converted to active drugs such as anticancer lysolipids and/or fatty acid drug derivatives. The PLA2 hydrolysis products will furthermore act as locally generated permeability enhancers that promote the absorption of the released drugs across the cancer cell membranes into putative intracellular target sites.

LiPlasome Pharma’s innovative prodrug and drug delivery concept allows for intravenous transport of high concentrations of anticancer drugs directly to the tumor target. In this way it is possible, without any prior knowledge of the position and size of the tumor, to release the anticancer drugs specifically at the tumor target site. This form of targeted drug delivery is particularly useful for transport of anticancer drugs, which are often mutagenic and extremely toxic against both cancer and healthy cells.

 

About Phospholipase A2 - the Trigger

Secretory phospholipase A2 belongs to a family of small (14 kDa) interfacially active enzymes that catalyze the hydrolysis of the ester bond in the sn-2 position of phospholipids, producing free fatty acids and lysolipids. PLA2 is only weakly active on monomeric lipid substrates but very active on organized lipid substrates such as micelles and liposomes. Furthermore, the enzyme’s activity and its mode of action is to a large extent controlled by the physical biomaterial properties and in particular the microstructure of the lipid substrate.

The degradation of the liposomal drug carrier and the release rate of the encapsulated drugs will be determined by the lability of the lipid substrate towards PLA2 hydrolysis as well as on the local concentration of PLA2 in the diseased cancer tissue. A fundamental understanding of the biomaterial properties of the lipid nanocarriers, specifically the surface properties and the microstructure forms the basis for a rational development of the performance of LiPlasome Pharma’s targeted drug delivery systems.