Nanodelivery of Molecular Therapies
(IMAGE: PHOTOS.COM/MELISSA MCEVOY)
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Nanotechnology offers an unprecedented opportunity in the rational delivery of drugs and vaccines (1, 2–4). Examples of nanotechnology
applied in pharmaceutical product development include organic nano-platforms such as polymeric, lipid (e.g., liposomes, nanoemulsions,
and solid–lipid nanoparticles), self-assembling structures, and dendrimers as well as certain inorganic nano-platforms including
metal (e.g., gold and silver), and silica-based nanostructures. Nano-sized delivery systems offer numerous advantages: small
particle size, narrow size distribution, protective insulation of drug molecules to enhance stability, surface features for
target-specific localization, specific types of materials that respond to an applied stimulus, the ability to deliver multiple
therapeutic payloads in a single formulation, and temporal control over their release, combination of drugs with electromagnetic
energy delivery for synergistic therapeutic effects, and the opportunity to combine imaging modality and drugs to monitor
the therapeutic effects in real time (2, 3, 5–8). The latter is significant for implementing the personalized medicine paradigm
(9, 10).
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.
References
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).
