Targeted Therapeutics

We are interested in delivering drugs directly to the site of injury.

(1) Cellular Analogues

Molecular level control over membrane surface chemistry allows cells to alter their binding affinity. Cells dynamically control their local molecular density, diffusivity, and membrane elasticity by organizing the ensemble of lipids, sugars, and proteins on their membranes. One model system mimics leukocyte-endothelial cell adhesions by complementing the assembly of molecules on cytokine-activated endothelial cell surfaces. Using a systematic approach, we have demonstrated that the complementary organization of molecules on drug delivery vehicles relative to cell membrane receptors is critical for achieving strong, cooperative binding. Understanding how cells use molecular level organization to orchestrate adhesion events may allow the design of model bilayer surfaces with engineered binding affinity.

Gunawan R, Auguste DT. Immunoliposomes that target endothelium in vitro are dependent on lipid raft formation. Molecular Pharmaceutics 2010; 7(5):1569-1575.

Gunawan R, Auguste DT. The role of antibody synergy and membrane fluidity in the vascular targeting of immunoliposomes. Biomaterials 2010; 31(5):900-907.

Gunawan R, Almeda D, Auguste DT. Complementary targeting of liposomes to IL-1 and TNF-α activated endothelial cells via the transient expression of VCAM-1 and E-selectin. Submitted.

(2) Bioresponsive Drug Delivery

We investigate the use of stimuli-responsive polymers to alter the release profile of drugs and genetic materials from their carriers. Methods to trigger release can be used to increase the localization of chemotherapeutics within tumors and the efficiency of DNA and siRNA delivery.

You J, Almeda D, Ye GJC, Auguste DT. Bioresponsive matrices in drug delivery. Journal of Biological Engineering 2010; 4:15.

You J, Auguste DT.  The effect of swelling and cationic character on gene transfection by pH-sensitive nanocarriers.  Biomaterials 2010; 31(26):6859-6866.

You J, Auguste DT.  Nanocarrier cross-linking density and pH sensitivity regulate intracellular gene transfer.  Nano Letters 2009; 9(12):4467-4473.  Highlighted in MRS Bulletin 2010; 35.

You J, Auguste DT.  Feedback-regulated paclitaxel delivery based on poly(N,N-dimethylaminoethyl methacrylate-co-2-hydroxyethyl methacrylate) nanoparticles.  Biomaterials 2008; 29(12):1950-1957.