Controlled Drug Delivery Systems: An Overview of the Field

Prof. Allan S. Hoffman, ScD. Bioengineering Department University of Washington Seattle WA, 98195, USA

There is great interest around the world in the drug delivery field.

It is one of the most active areas of R&D in polymeric biomaterials.

Significant drug delivery systems (DDS) developed from the 1970s to the present
Transdermal patches Implanted, drug-loaded, degradable microparticles Implanted, drug-loaded silicone rods Soluble polymer-drug conjugates Osmotic pressure-driven capsules for oral DD Drug-loaded polymer coatings for stents Special inhalers for pulmonary DD Colon-specific DDS Stealth liposomes Enteric coatings for oral tablets

Tissue engineering implants are an emerging application of drug delivery!

First, a few words about the principles for designing a drug delivery system based on how and where the drug will act in the body.

To design a DDS it is important to know how much drug is needed? at what delivery rate? over what period of time (duration)? with what bioavailability? acting at which sites or on which cells?

Where do drugs act in the body? In the circulation In the tissue space (ECM) At the cell membrane Inside the cell

The Dose-Effect Relationship

Dose Pharmacokinetics (PK) Plasma Concentration Pharmacodynamics (PD) Effect

The Dose-Effect Relationship

Dose Dont forget--every person has

a different dose-effect with each Pharmacokinetics (PK) drug and dosetherefore, a large population needed to design an Plasmais Concentration effective dosage formulation.
Pharmacodynamics (PD) Effect

L. Maggi, U. Conti, Geomatrix Technology, Segno & Forma, 2003

Pharmacokinetics / Pharmacodynamics
Drug in blood Drug concn. Concentration
7 6 5 4 3 2 1 0 0 5 10 15 20 25

ADME Absorption and Distribution

Drug 3.5 effect

3 2.5 D ru g Effect

Large population

2 Metabolism and Elimination 1.5 1 0.5 0 0 2 4 6 8 10

Time Time

Drug Concentration Drug concn.

Pharmacokinetics (PK) What the body does to the drug Fairly easy to measure (e.g., biodistribution) Used to get to the PD

Pharmacodynamics (PD) What the drug does to the body Less well understood PD has clinical relevance

Pharmacokinetics of Pills and Shots vs. Controlled Drug Delivery

Toxicity possible above range (TI)

Also Therapeutic Index (TI)

Drug wasted below range (TI)

(pills or injections)

Controlled release also results in better patient compliance!

Courtesy of Prof. Emo Chiellini

CONTROLLED RE LEASE SYSTE MS

Rationale for Controlled Release of Drugs

Increased patient compliance less frequent dosing more acceptable (eg, needle-less) Safety Therapeutic can control PK to remain within Therapeut Index window Improved therapy can time release environmentally-responsive systems Decreased cost lower doses->more efficient use of drug Greater profits patent extension fo r drug controlled release feature more profitable controlled release feature more profitable

An example of economic rationale for controlled release

Another example of potential profitability of controlled release

Harvard Health Letter July 2004

Harvard Health Letter July 2004

Some Unsolved Problems with DDS

Oral delivery of proteins Effective delivery of low solubility drugs Feedback DDS using body signals to stimulate delivery of specific amount of drug Chrono-DDS, delivery based on known circadian rhythms of body organs (perhaps combined with Feedback DDS) Pharmacogenomics, drug indications and prescriptions based on ones genetic makeup (many ethical issues)

A.S. Hoffman, UW, Seattle, WA

How would you design an overview lecture on drug delivery systems (DDS)? There are many different possibilities

Design of Drug Delivery Systems (DDS)

This lecture could be organized according to:

ROUTES OF DELIVERY (eg, Oral, Injected, Transdermal...) BODY SITE OF DELIVERY (eg, Blood, Liver, Lungs, Pancreas) LOCAL SITE FOR ACTION (eg, Body Fluids, Cell Surface, Intracellular) MECHANISM OF DELIVERY (eg, Drug Diffusion, Swelling, Degradation..) DISEASE (eg, Cancer, Glaucoma, Diabetes..)

Design of Drug Delivery Systems (DDS)

This lecture will be organized according to:

ROUTES OF DELIVERY (eg, Oral, Injections, Transdermal...) BODY SITE OF DELIVERY (eg, Blood, Liver, Lungs, Pancreas) LOCAL SITE FOR ACTION (eg, Body Fluids, Cell Surface, Intracellular) MECHANISM OF DELIVERY (eg, Drug Diffusion, Swelling, Degradation..) DISEASE (eg, Cancer, Glaucoma, Diabetes..)

Routes of Drug Delivery

Oral
Gastric, enteric, colonic

Injections and Implants

Intra-venous (IV), sub-cutaneous (SQ), intra-muscular (IM), intra-epidural (IE), intra-cranial (IC)

Transdermal
Skin

Mucosal
Ophthalmic, nasal, vaginal, anal, buccal, sub-lingual

Inhalation
Pulmonary