Gold NanoparticlesA Novel Nanoparticulate Drug Delivery System| Lejo. R. Prasad / 000392026Drug Design and Delivery CHEM-1081 Dr. Dionysios Douroumis
A Novel Nanoparticulate Drug Delivery System
The use of nanoparticles is a fairly recent development and has proved to be an ideal platform for the target specific delivery of various therapeutic agents. Nanoparticles recently over the last decade, different nanomaterial have been used to design various delivery vehicles, which includes, liposomes, dendrimers, polymers, nanotubes and nanorods. Metallic nanomaterial’s have attracted interest for use not only in drug delivery but also in various other fields due to their properties. A metal that has been of considerable study in this aspect is gold. Since the early 1950’s gold nanoparticles (GNPs) have been used as diagnostic indicators and therapeutics. One of the requirements for effective therapy is the efficient and targeted release of various therapeutic agents. GNPs are of the highest quality and their unique chemical and physical properties can be exploited for transporting and unloading of various therapeutic agents (Thassu, D, 2007). Therefore, GNPs have been found to be an ideal candidate for the delivery of various payloads such as small drug molecules and large biomolecules like proteins, DNA or RNA. Synthesis
The ease of synthesis of GNPs is one of its main advantages. Monodisperse particles can be made in sizes ranging from 1nm upto 150nm with very narrow size distributions (Thassu, D, 2007). Depending on the size and functional moieties required of the GNP different synthetic methods could be used (Table 1). Using the one-pot protocol developed by Schiffrin et al (1994) (Diagram 1), a wide variety of monolayer protected clusters (MPCs), which are GNPs that bear functional moieties by being anchored to thiol linkers in their monolayers. In this procedure, AuCl4- salts undergo reduction by NaBH4 in the presence of the desired thiol capping ligand or ligands. The resulting particles can be made to have core sizes of 1.5nm to approximately 6nm by varying the thiol gold stoichiometry. The functions of MPCs can be further extended by making MPCs into mixed monolayer protected clusters (MMPCs) or synthesizing the MMPCs directly. This is done via the place-exchange reaction developed by Murray, where foreign thiols displace the ligands that are already on MPCs. This creates a wide range of functionality at the particle surface and allows the addition of moieties including biocompatible oligo (ethylene glycol) (OEG) and poly (ethylene glycol) (PEG) groups. The addition of these groups also protects GNPs from opsinization, when they enter circulation and prevents proteins called opsins, which includes immunoglobins, complement proteins C1 & C3 and apoliproteins, from binding to the metallic nanoparticle surface and effectively tagging the nanoparticles so as to be recognized by specialized macrophages in the liver called Kupffer cells, and rapidly removed from circulation by the reticuloendothelial system (RES) (Thassu, D, 2007).
Core Size (d)| Synthetic Methods| Capping Agents|
1-2 nm| Reduction of AuCl(PPh3) with diborane or sodium borohydride| Phosphine| 1.5-5 nm| Biphasic reduction of HAuCl4 by sodium borohydride in the presence of thiol capping agents| Alkanethiol| 10-150 nm| Reduction of HAuCL4 with sodium citrate in water| Citrate| Table 1: Synthetic methods and capping agents used for GNPs of different core sizes
Diagram 1: Formation of MPCs using the Schriffin reaction and MMPCs using Murray’s place-exchange reaction Drug delivery using GNPs
As mentioned previously, the use of GNPs in drug delivery systems is ideal as it allows the loading of therapeutic drugs to a large degree, allowing it to act as drug reservoir. The use of drug delivery systems...