Biomaterials, Drug Delivery, Nanotechnology and Bioengineering Nicholas A. Peppas Center for Biomaterials, Drug Delivery, Bionanotechnology and Molecular Recognition Departments of Chemical Engineering, Biomedical Engineering, and Division of Pharmaceutics The University of Texas at Austin Austin, Texas 78712, USA

“Smart” Drug Delivery The future of drug delivery systems will involve smart systems These will address the issue of keeping the drug at the desired therapeutic level in the body thus avoiding frequent administration Systems use detection of chemical signals in the body to prompt the release of drugs The ultimate goal is to administer drugs The ultimate goal is to administer drugs at the right time, at the right dose anywhere in the body with specificity and efficiency

Polymeric Carrier Tight Junction Mucosa Protein Proteolitic Enzymes Oral Delivery of Proteins Challenges Protection of the drug from: –The acidic environment in the stomach –Degradation by proteolytic enzymes in the GI tract Penetration and absorption of drug across the intestinal mucosa and epithelium Stomach pH ~2

Complexation and pH Responsive Hydrogels   Complexed Small mesh size Low pH Uncomplexed Increased mesh size High pH H2CH2CC CH 3 CO [ O CH 2 CH 2 ] n OCH 3 H2CH2CC CH 3 HOOC H2CH2CC CH 3 CO [ O CH 2 CH 2 ] n OCH 3 H2CH2CC CH 3 - OOC Protect drug Release drug

In Vivo Study with pH-Responsive Complexation Hydrogels P(MAA-g-EG) microspheres loaded with insulin Administered to diabetic rats  40% drop in blood glucose levels

NIH 2-3 positions

NIH/NCI 1-2 positions

NSF 1 position

System-Responsive Therapy: Control-Based Design of Biomedical Systems Configurational Biomimetic Imprinting Molecular key (template molecule) –Small molecules Drug substances, amino acids, steroid hormones –Large molecules Nucleic acids, proteins –Cells and viruses Lock (polymer building blocks) –Functional monomers –Cross-linkers Making “artificial locks” for “molecular keys”

Configurational Biomimetic Imprinting Solvent Initiator Template Polymerization Extraction and drying Monomers

BioMEMS Sensor Platform Pattern environmentally responsive hydrogels onto silicon microcantilevers to create a BioMEMS/MEMS sensor device. Laser beam θ Polymer Silicon φ > θ Laser beam φ Change in analyte, pH, temperature etc.  hydrogel swells

System-Responsive Therapy: A Bright Future Need for advanced intelligent materials, more reliable devices, miniaturized systems Society asks for improved treatment of disease, advanced detection and therapy, and cost effective processes Improvement of quality of life is important

CancerInsulinsiRNA Recognitive External Triggering Mary Brandon Jenny Bill Cody David Amey Maggie Diane