Biomaterials, Drug Delivery, Nanotechnology and Bioengineering

Nicholas A. PeppasNicholas A. PeppasCenter for Biomaterials, Drug Delivery, Bionanotechnology Center for Biomaterials, Drug Delivery, Bionanotechnology

and Molecular Recognition and Molecular Recognition

Departments of Chemical Engineering, Biomedical Engineering,Departments of Chemical Engineering, Biomedical Engineering,and Division of Pharmaceuticsand Division of Pharmaceutics

The University of Texas at AustinThe University of Texas at AustinAustin, Texas 78712, USAAustin, Texas 78712, USA

““Smart” Drug DeliverySmart” Drug Delivery

The future of The future of drug delivery systemsdrug delivery systems will involve will involve smart systemssmart systems

These will address the issue of These will address the issue of keeping the drug at the desired keeping the drug at the desired therapeutic leveltherapeutic level in the body in the body thus avoiding frequent thus avoiding frequent administrationadministration

Systems use Systems use detection of chemical signals in the bodydetection of chemical signals in the body to prompt to prompt the release of drugsthe 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 ProteinsOral Delivery of Proteins

ChallengesChallengesProtection of the drug from:Protection of the drug from:– The The acidicacidic environment in the environment in the

stomachstomach– DegradationDegradation by proteolytic by proteolytic

enzymes in the GI tractenzymes in the GI tract

Penetration and absorption Penetration and absorption of drug across the intestinal of drug across the intestinal mucosa and epitheliummucosa and epithelium

Stomach pH ~2

Complexation and pH Responsive HydrogelsComplexation and pH Responsive Hydrogels

Complexed Small mesh size Low pH

Uncomplexed Increased mesh size High pH

H2C C

CH3

C O

[ O

CH2CH2 ]n

OCH3

H2C C

CH3

HOOC

H2C C

CH3

C O

[ O

CH2CH2 ]n

OCH3

H2C C

CH3

-OOC

Protect drug

Release drug

Systemic Circulation

Polymeric Carrier

TightJunction

Mucosa

Protein

ProteoliticEnzymes

In VivoIn Vivo Study with pH-Responsive Study with pH-Responsive Complexation HydrogelsComplexation Hydrogels

P(MAA-g-EG)P(MAA-g-EG) microspheres microspheres loaded with insulinloaded with insulin

Administered to diabetic ratsAdministered to diabetic rats 40% drop in blood glucose 40% drop in blood glucose levelslevels

NIH 2-3 positions

NIH/NCI 1-2 positions

NSF 1 position

System-Responsive Therapy:System-Responsive Therapy:Control-Based Design of Biomedical SystemsControl-Based Design of Biomedical Systems

Configurational Biomimetic ImprintingConfigurational Biomimetic Imprinting

Molecular key Molecular key

(template molecule)(template molecule)– Small moleculesSmall molecules

Drug substances, amino Drug substances, amino acids, steroid hormonesacids, steroid hormones

– Large moleculesLarge moleculesNucleic acids, proteinsNucleic acids, proteins

– Cells and virusesCells and viruses

Lock Lock

(polymer building blocks)(polymer building blocks)– Functional monomersFunctional monomers– Cross-linkersCross-linkers

Making “artificial locks” for “molecular keys”

Configurational Biomimetic ImprintingConfigurational Biomimetic Imprinting Solvent

Initiator

Template

Polymerization

Extractionand drying

Monomers

BioMEMS Sensor PlatformBioMEMS Sensor Platform

Pattern Pattern environmentally responsive environmentally responsive hydrogels onto silicon microcantilevershydrogels onto silicon microcantilevers to to create a BioMEMS/MEMS sensor device.create a BioMEMS/MEMS sensor device.

Laser beam

θ

Polymer

Silicon

φ > θ

Laser beam

φ

Change in Change in analyte, pHanalyte, pH, , temperaturetemperature etc. etc. hydrogel swells hydrogel swells

System-Responsive Therapy:System-Responsive Therapy:A Bright FutureA Bright Future

Need for Need for advanced intelligent materialsadvanced intelligent materials, more , more reliable devices, reliable devices, miniaturizedminiaturized systems systems

Society asks for Society asks for improved treatmentimproved treatment of of disease, advanced disease, advanced detectiondetection and and therapytherapy, and , and cost effective processescost effective processes

Improvement of Improvement of quality of lifequality of life is important is important

CancerInsulin siRNA Recognitive External Triggering

Mary

Brandon

Jenny

BillCody

David

Amey

MaggieDiane