Chapter 16. Drug Delivery

Jianjun Cheng and Suzie Hwang Pun

Therapeutic drugs are usually delivered in bolus doses, either orally or by injection. These administrations result in initial blood concentrations that are higher than required levels, followed by a decrease to subtherapeutic levels due to drug degradation and excretion. Therefore, drugs must be given frequently to maintain therapeutic drug concentrations (Figure 16-1). In the 1970s, researchers introduced the concept of controlled drug delivery by using carriers to release drugs in a sustained manner. In the ideal case, drugs are gradually released from a depot so that the drug concentration is maintained at an effective level over a long period. An example of one such success is Gliadel, the first FDA-approved biopolymer drug-delivery system for treatment of brain cancer. Gliadel wafers are implanted into the brain after tumor resection. There, the wafers locally release carmustine (a chemotherapeutic drug) for several months.

Figure 16-1. Schematic expression of plasma drug level of bolus dose and controlled release.

Many other promising drugs never make it to clinical trials because of inherent pharmacological drawbacks. Low-molecular-weight drugs, such as most chemotherapy drugs, are usually insoluble and highly toxic. Protein and nucleic acid drugs usually have poor stability in physiological conditions. It is therefore essential for these drugs to be protected en route to their target disease sites in the body. Drug-delivery systems may rescue potential drug candidates by increasing solubility and stability.

Drug-delivery technologies are developed to improve the safety and efficacy of drugs, to ensure better patient compliance, and to improve the shelf life and stability of therapeutic products. Controlled drug release involves the combination of a biocompatible material or device with a drug to be delivered in a way that the drug can be delivered to and released at diseased sites in a designed manner.

The major routes of drug administration are oral, inhalation, injection, and transdermal delivery. The most well-known route is oral drug delivery, which accounted for about 50 percent of the market as of 2003. The other routes of administrationinhalation, transdermal, injection and implantation, and nasal deliveryaccount for the remaining market share at 19 percent, 12 percent, 10 percent, and 7 percent, respectively. In the past 30 years, the field of drug delivery has been undergoing rapid development and has attracted attention from both academia and pharmaceutical industries. According to a recent report, the U.S. market alone for drug delivery is estimated at $43.7 billion in 2003 and is expected to grow more than 11 percent annually in the next five years.^[1]