Looking at the technologies
Pegylation, or the attachment of a polyethylene glycol moiety, is one example of a commercialized drug-delivery approach that
can employ nanocarriers (3). Pegylation is used as a means of modifying naturally occurring proteins to improve the pharmacodynamics
of the protein (4). Several commercial products using pegylated-based systems, and which are broadly classified as nanocarriers,
are pegylated interferon and peglyated granulocyte colony-stimulating factor (3–6). Pegasys (peginterferon alfa-2a) by Roche
(Basel, Switzerland) and Nektar Therapeutics (San Carlos, CA) and Peg- Intron (pegylated-alfa interferon 2b) by Schering-Plough
(Kenilworth, NJ) and Enzon Pharmaceuticals (Bridgewater, NJ) are two examples of pegylated interferons, and Neulasta by Amgen
(Thousand Oaks, CA) is an example of a peglyated granulocyte colony-stimulating factor. Pegylated-based formulations address
pharmacologic limitations such as toxicity, poor solubility, or a limited half-life.
Several commercial products use nanocrystallines as a drug-delivery platform. Elan Drug Technologies, a business unit of Elan
(Dublin, Ireland), for example, uses its NanoCrystal technology to improve the delivery of poorly water-soluble drugs by transforming
them into nanometer-sized particles, typically less than 2000 nm in diameter. These particles are produced by milling the
drug substance using a proprietary wet-milling technique, according to company information. The NanoCrystal particles of the
drug are stabilized against agglomeration by surface adsorption of select stabilizers. The result is an aqueous dispersion
of the drug substance that behaves like a solution, a nanocrystal colloidal dispersion, which can be processed into finished-dosage
Elan's NanoCrystal technology is used in five US-approved products. These products include Wyeth's (Madison, NJ) Rapamune
(sirolimus), Merck & Co.'s (Whitehouse Station, NJ) Emend (aprepitant), Abbott Laboratories' (Abbott Park, IL) Tricor (fenofibrate),
and Par Pharmaceutical's (Woodcliff Lake, NJ) Megace ES (megestrol). In August 2009, a fifth product was approved, Invega
Sustenna (Johnson & Johnson, New Brunswick, NJ), a long-acting injectable form of paliperidone palmitate. Elan says it is
the first approval of a long-acting injectable formulation using its technology.
Albumin-bound paclitaxel is another example of a commercialized nanoparticle drug-delivery platform. Abraxis BioScience's
(Los Angeles) Abraxane for injectable suspension (paclitaxel protein- bound particles for injectable suspension, albumin-bound)
is an anticancer drug that uses the company's "nab" technology platform. The drug is an albumin-bound taxane particle of approximately
130 nm. Albumin is a protein that acts as the body's key transporter of nutrients and other water-insoluble molecules and
selectively accumulates in tumor tissues. In the case of Abraxane, by wrapping the albumin around the active drug, the drug
can be administered to patients at higher doses, thereby delivering higher concentrations of paclitaxel to the tumor site
than solvent-based paclitaxel. Abraxane is approved for treating metastatic breast cancer. It is currently in various stages
of investigation for treating expanded applications for metastatic breast, non small-cell lung, melanoma, pancreatic, and
Advances from the pipeline
Nanodrugs under clinical development include candidates using liposomal and polymeric platforms such as pegylation as well
as composition polymers (3). For example, Supratek Pharma (Montreal) is developing an anticancer drug using its Biotransport
nanocomposition of block copolymers for a pluronic block–copolymer formulation of doxorubicin. The drug is in preclinical
and clinical development for various cancers. The Biotransport compositions consist of an active pharmaceutical ingredient
with specific polymer combinations to achieve improved biological response and targeted drug delivery. The resulting nanosystems
range from 10–100 nm in size, according to the company. Cell Therapeutics (Seattle) is developing Opoxio (formerly Xyotax)
(paclitaxel poliglumex, CT-2103), a chemotherapeutic that links paclitaxel to a biodegradable polyglutamate polymer.
Dendrimers and nanogold particles are examples of other nano-based delivery systems. Starpharma (Melbourne, Australia), for
example, has several products and platforms under development using dendrimer technology. The synthesis of dendrimers involves
a core molecule with branching groups to which other branching molecules are added in layers; each new layer is called a generation.
The final generation can incorporate additional active groups that give the particular functionality to the dendrimer. The
linkage of the active to the dendrimer nanoparticle is designed to extend half-life, reduce toxicity, improve drug solublization,
and target delivery, according to the company.
Cytimmune Sciences (Rockville, MD) is developing colloidal gold-based nanomedicines. CytImmune's lead drug candidate, Aurimune
(CYT-6091), consists of recombinant human tumor necrosis factor-alpha (TNF) bound to the surface of pegylated colloidal gold
nanoparticles. The company says by simultaneously binding TNF and pegylated-thiol to the surface of colloidal gold nanoparticles,
the therapeutic payload can travel safely through the bloodstream and avoid immune detection and is preferentially delivered
to the site of disease. At 27 nm, Aurimune primarily and preferentially exits the circulation through leaky, newly formed
vasculature at tumor sites, thereby selectively passing through gaps in blood-vessel walls. In addition to Aurimune, the company
is developing other pegylated collodial gold-bound TNF systems of other anticancer drugs, including paclitaxel, doxorubicin,
interleukin-12, and interleukin-2.
Patricia Van Arnum is a senior editor at Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072, email@example.com
1. Mansoor M. Amiji, "Nanodelivery of Molecular Therapies," Pharm. Technol. online exclusive, Dec. 2007,
pharmtech.findpharma.com/pharmtech/Special+Report/Whats-Next-In-Drug-Delivery/ArticleStandard/Article/ detail/477141, accessed Sept. 7, 2009.
2. FDA, "Frequently Asked Questions on Nanotechnology," (Rockville, MD),
http://www.fda.gov/ScienceResearch/SpecialTopics/Nanotechnology/FrequentlyAskedQuestions/default.htm, accessed Sept. 7, 2009.
3. L. Jia, "Global Investment in Nanotechnology," presented at the American Association of Pharmaceutical Scientists Annual
Meeting, Atlanta, GA, November 2008.
4. M.D. Howard et al., "PEGylation of Nanocarrier Drug Delivery Systems: State of the Art," J. Biomedical Nanotechnol.
4 (2), 133–148 (2008).
5. T. Thomas and G. Foster, "Nanomedicines in The Treatment of Chronic Hepatitis C—Focus on Pegylated Interferon alpha-2a,"
Int. J. Nanomedicine.
2 (1), 19–24 (2007).
6. D. Peer et al., "Nanocarriers as an Emerging Platform for Cancer Therapy," Nat. Nanotechnol. 2 (12), 751–760 (2007).