Nanodelivery of Molecular Therapies
Despite these seemingly clear advantages, the number of currently approved nanotechnology-based products for routine clinical use is fairly limited. Select examples include doxorubicin in long-circulating liposomes ("Doxil") and paclitaxel in albumin nanoparticles ("Abraxane") for systemic administration, rapamycin in a nanocrystal formulation for oral administration ("Rapamone"), and estradiol in oil-in-water nanoemulsion ("Estrasorb") for topical application. The major barriers to clinical translation of nanotechnology-based products are mainly focused on scale-up and manufacturing issues, as well as safety concerns. Due to the inherent complexity of some of the nanosystems, large-scale manufacturing under current good manufacturing practices guidelines and appropriate quality control can become a major stumbling block. Certain nanomaterials, such as fullerenes, carbon nanotubes, and quantum dots have excellent properties, but their systemic distribution and clearance profiles, tissue and cellular interactions, and associated toxicity, especially upon chronic in vivo administration, have not been clearly addressed. The biodistribution of a nano-encapsulated drug will be quite different from that of the free drug. Therefore regulatory agencies will require comprehensive preclinical dose-escalating toxicity studies in multiple animal species before they can approve the final product. The associated complexities and higher cost of these studies profoundly affects clinical development. These concerns become even more magnified with complex nanosystems having multiple therapeutic payloads and additional targeting and imaging functionalities.Based on the advantages and certain challenges for nanotechnology-based delivery system, judicious selection of materials and products for initial preclinical and clinical evaluation will be essential. Several products based on liposomes, nanoemulsions, polymeric nanoparticles, and gold nanoparticles are currently in advanced preclinical and clinical stages. Success of these trailblazer nano-products will provide the essential impetus for further development of more sophisticated technologies with significant benefits to patients.
Mansoor M. Amiji, RPh, PhD, professor and associate department chairman, Department of Pharmaceutical Sciences in the School of Pharmacy, and codirector of the Nanomedicine Education and Research Consortium, Northeastern University. Amiji was named an AAPS fellow at the 2007 AAPS annual meeting in San Diego, CA.
1. M. Rawat et al. "Nanocarriers: Promising Vehicle for Bioactive Drugs, Biol. Pharm. Bull. 29 (9), 1790-1798 (2006).
2. S.B. Tiwari and M.M. Amiji. "A Review of Nanocarrier-based CNS Delivery Systems," Curr. Drug. Deliv. 3 (2), 219-232 (2006).
3. V.P. Torchilin. "Recent Approaches to Intracellular Delivery of Drugs and DNA and Organelle Targeting," Annu. Rev. Biomed. Eng. 8, 343-375 (2006).
4. L.E. van Vlerken and M.M. Amiji. "Multi-Functional Polymeric Nanoparticles for Tumor-targeted Drug Delivery," Expert Opin. Drug Deliv. 3 (2), 205-216 (2006).