Drug Delivery Technology

NAN OTECHN OLOGY

immunogenicity, prolongs plasma half-life, and enhances protein stability. Polymer-drug conjugation promotes tumor targeting through the enhanced permeability and retention effect, and at the cellular level following endocytic capture, allows lysosomotropic drug delivery. Ceramic nanoparticles are inorganic systems with porous characteristics that have recently emerged as drug vehicles. ⁴

Dendrimers

Drug Delivery Technology February 2009 Vol 9 No 2

Dendrimers have emerged as an important class of drug-encapsulating nanoparticles as a result of their unique architecture and macromolecular characteristics. Dendrimers are synthetic, highly branched, spherical, monodispersed macromolecules with an average diameter of 1.5 to 14. 5 nm. A typical dendrimer molecule consists of an initiator core, highly branched layers composed of repeating units, and multiple active terminal groups. The architectural design of dendrimers provides a high level of control over the dendrimer size, shape, branching length, and surface functionality.

Biodegradable polyester dendrimers based on 2,2-bis(hydroxymethyl)- propanoic acid monomers have been developed for intracellular release of doxorubicin after hydrolysis of the hydrazone linkage. The promising properties of polyester dendrimers as a drug delivery system has led to further studies based on tunable architectures and molecular weights to optimize tumor accumulation. In a comparative study with Doxilin C- 26 colon carcinoma-bearing mice, the polyester dendrimer drug conjugate shows similar efficacy to the doxorubicin-liposome formulation. ⁵

Nucleic Acid-Based
Nanoparticles

In nucleic acid-based nanoparticles,

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DNA and RNA macromolecules can be

used as substrates for developing therapeutic and imaging nanocarriers. A multivalent DNA delivery vehicle, with an average size of 100 nm, was recently reported for simultaneous targeted drug delivery, imaging, and gene therapy. Targeted multifunctional RNA nanoparticles ( 25 to 40 nm) have also been developed with a trivalent RNA core, RNA aptamers for targeting, and siRNAs for therapeutic effect. ⁶

Polymeric Nanoshells

Polymeric nanoshells consist of diblock copolymers that can be assembled

into a core/shell structure. In general, nanoshells are made by self-assembly of oppositely charged polymers covering the surface of the drug’s nanoparticles. Therefore, the drug-release rate is controlled by the chemistry of the polymers and the diffusion coefficient through the polymeric layer. For example, nanoshells encapsulating doxorubicin have been synthesized using amphiphilic tercopolymer poly(N-isopropylacrylamide-co-N,N- dimethylacrylamide-co-10- undecenoicacid) that can trigger intracellular doxorubicin release at pH 6. 6.