Challenges and Future Opportunities

One of the main drivers for the development of new pulmonary drug delivery systems has been the potential for noninvasive systemic delivery of protein and peptide compounds. The systemic delivery of macromolecules via the airways would overcome the inconvenience and cost associated with current methods of administration (injection), and appears likely given the large surface area of the airways and the thin pulmonary epithelium. Most research has concentrated on pulmonary delivery of insulin for the treatment of diabetes. Recently, one insulin product has completed phase three studies and is now undergoing review by European regulatory agencies for marketing approval. 

Specific formulation strategies need to be employed for macromolecule compounds. An excellent review of protein stability in aqueous solutions has been published by Chi et al. (92). In addition to solution stability of proteins and peptides, aerosolization may result in significant surface interfacial destabilization of these compounds if no additional stabilization excipients are added. This is due to the fact that protein molecules are also surface active and adsorb at interfaces. The surface tension forces at interfaces perturb protein structure and often result in aggregation (92). Surfactants inhibit interface-induced aggregation by limiting the extent of protein adsorption (92). 

Clark A. Pulmonary delivery technology recent advances and potential for the new millennium. In Hickey AJ, ed. Pharmaceutical Inhalation Aerosol Technology. 2d ed. New York Marcel Dekker, 2004. 

Molina MJ, Rowland FS. Stratospheric sink for chlorofluoromethane chlorine atom catalyzed destruction of ozone. Nature 1974 274 810-812. 

Patton JS. Deep-lung delivery of therapeutic proteins. Chem Tech 1997 27(12) 34—38. 

---

Success does not come without effort. If you truly want to be successful, make a commitment to spend the time you need to improve your chemistry skills. When you achieve chemistry success, you have laid the foundation for future challenges and opportunities. 

Future challenges and opportunities antibody-directed intracellular drug delivery... 

FUTURE CHALLENGES AND OPPORTUNITIES ANTIBODY-DIRECTED INTRACELLULAR DRUG DELIVERY... 

---