Pre-Clinical Studies

Because APCs are vital to neurodegenerative diseases as well as cancer growth and metastasis, we designed the CLR-TargoSphere® to deliver therapeutic payloads to dendritic cells, monocytes, macrophages, Tumor-Associated Macrophages, and activated Cytotoxic T-Lymphocytes (CTLs).

Our in-vitro studies have demonstrated that the CLR-TargoSphere® has a preferential affinity for M2 macrophages. Because paclitaxel, in addition to its apoptotic activity, is known to influence the enhancement and anti-tumor activity of M1 tumoricidal macrophages, preferential delivery to type-2 TAMs may inhibit the development of M2 (tumorigenic) macrophages (1, 2).

Biodistribution studies conducted by Rodos BioTarget GmbH with subcutaneous administration of the CLR-TargoSphere® in the LEW rat model demonstrated distribution of the active pharmaceutical agent to the central nervous system. Imaging studies revealed that the CLR-TargoSphere® crossed the Blood-Brain Barrier (BBB) and delivered the API intracellularly to astrocytes, with marked concentration in perivascular spaces of brain and areas rich in glial cell populations.

A preliminary in-vivo Proof-of-Concept study was conducted by Augustus BioTarget at the Southern Research Institute in Birmingham, AL, USA, using the carbohydrate mannose, attached to an analogue of paclitaxel and targeted to circulating monocytes in an athymic NCr nu/nu mouse model. Mice inoculated intracerebrally with a human U251 human glioblastoma brain tumor cell line showed a statistically significant extended overall survival and decreased toxicity with the mannosylated paclitaxel analogue, when compared to treatment with unmodified paclitaxel.

The goals of in-vitro and in-vivo preclinical development of Alzheimer’s disease treatment in the US, Germany, and Italy:

  1. Encapsulation and characterization of the APIs, gemcitabine, paclitaxel, and curcuminin the CLR-TargoSphere®.
  2. Targeting the brain in a transgenic murine mouse Alzheimer’s disease model with paclitaxel and curcumin. A dual strategy is being conducted to inhibit the development of abnormal protein tau, and amyloid beta deposition.
  3. The treatment strategy for Alzheimer’s disease is to deliver CLR-TargoSphere®-encapsulated paclitaxel and curcumin to myeloid DCs, circulating monocytes and TAMs to cross the BBB and deliver the active agents to the perivascular spaces, astrocytes, and activated glial cells.