Drug delivery technologies have the potential to enable drug candidates with poor pharmaceutical or biopharmaceutical properties, both for macromolecule and traditional compounds. While there have been many success stories to date, the future offers even more promise. In this article, the author surveys the top ten areas in drug delivery looking forward.
"Those who talk about the future are scoundrels. It is the present that matters."
To be successful, a drug delivery technology must bring a real advantage to the patient (e.g., improved efficacy, safety, compliance), the caregiver (e.g., convenience), the care payer (e.g., a pharmacoeconomic advantage), and the company itself (e.g., increased sales, decreased cost of goods, extended patent life). This article will attempt to assess new drug delivery technologies likely to affect the market. In making this assessment, the author identified areas where improvements in delivery are most needed to create a "top ten list" of opportunities in drug delivery
ORAL DELIVERY OF PROTEINS
The biopharmaceutical market was valued at more than $70 billion in 2005.2 Most of these proteins are being administered by injection. Given patient preferences for less invasive routes of administration, one can only imagine what the sales for therapeutic proteins would be if they could be given orally. It is easy to see why many consider the oral delivery of proteins to be the holy grail of drug delivery.
Despite decades of work toward oral delivery of therapeutic proteins, progress has been fairly limited. This can be attributed to the multiple challenges faced in this area. First, the protein must survive the low pH of the stomach, which is typically pH 1.5–2 in fasting adults.3 Next the protein is exposed to numerous enzymes present in the gastrointestinal (GI) tract, many of which are designed to hydrolyze proteins.4
If one is able to overcome these obstacles, the protein still must be absorbed through the intestinal mucosa. Permeability of proteins through cell membranes is extremely low. Their large molecular weights and high hydrogen-bonding capacity,5 makes significant transcellular passive diffusion through membranes unlikely. Although the intercellular space between adjacent epithelial cells offers an aqueous pathway for protein diffusion,5 this space is limited by the presence of tight junctions, and provides a small surface area relative to the total epithelial surface. Finally, once absorbed, the protein must survive first-pass metabolism.
The therapeutic index and cost of goods of the protein will also be factors in determining the feasibility of oral protein delivery. Due to the hurdles described above, it is reasonable to expect low, variable bioavailability. Thus, proteins with a narrow therapeutic index or high cost of goods will not be ideal candidates.
PULMONARY DELIVERY OF PROTEINS AND PEPTIDES
On September 8, 2005, an FDA advisory committee panel recommended the approval of Exubera, which delivers insulin by the pulmonary route using Nektar Therapeutics' dry powder inhaler. This approval is impressive given the many hurdles it had to pass, including the narrow therapeutic index of insulin and the need for strict particle size control to reach the alveolar surface.