Drug Stability and Minimized Acid-/Drug-Catalyzed Phospholipid Degradation in Liposomal Irinotecan.

Therapeutics at or close to the nanoscale, such as liposomal irinotecan, offer significant promise for the treatment of solid tumors. Their potential advantage over the unencapsulated or free form of the drug is due in part to their altered biodistribution. For slow and sustained release, significant optimization of formulation is needed to achieve the required level of stability and allow long-term storage of the drug product.

Development of disulfide-stabilized Fabs for targeting of antibody-directed nanotherapeutics.

Antibody-directed nanotherapeutics (ADNs) represent a promising delivery platform for selective delivery of an encapsulated drug payload to the site of disease that improves the therapeutic index. Although both single-chain Fv (scFv) and Fab antibody fragments have been used for targeting, no platform approach applicable to any target has emerged. scFv can suffer from intrinsic instability, and the Fabs are challenging to use due to native disulfide over-reduction and resulting impurities at the end of the conjugation process.

Taphonomic experiments imply a possible link between the evolution of multicellularity and the fossilization potential of soft-bodied organisms.

The reliability of evolutionary reconstructions based on the fossil record critically depends on our knowledge of the factors affecting the fossilization of soft-bodied organisms. Despite considerable research effort, these factors are still poorly understood. In order to elucidate the main prerequisites for the preservation of soft-bodied organisms, we conducted long-term (1-5 years) taphonomic experiments with the model crustacean buried in five different sediments.

Targeting EphA2 in Bladder Cancer Using a Novel Antibody-Directed Nanotherapeutic.

Ephrin receptor A2 (EphA2) is a member of the Ephrin/Eph receptor cell-to-cell signaling family of molecules, and it plays a key role in cell proliferation, differentiation, and migration. EphA2 is overexpressed in a broad range of cancers, and its expression is in many cases associated with poor prognosis. We recently developed a novel EphA2-targeting antibody-directed nanotherapeutic encapsulating a labile prodrug of docetaxel (EphA2-ILs-DTXp) for the treatment of EphA2-expressing malignancies.

Formulation optimization of an ephrin A2 targeted immunoliposome encapsulating reversibly modified taxane prodrugs.

Ephrin A2 targeted immunoliposomes incorporating pH-sensitive taxane prodrugs were developed for sustained delivery of active drug to solid tumors. Here we describe the systematic formulation development and characterization of these immunoliposomes. We synthesized both paclitaxel and docetaxel prodrugs to formulate as ephrin A2-targeted liposomes stabilized in the aqueous core with sucroseoctasulfate (SOS).