Christopher M. Barnett, Martin R. Lees, Anthony D.M. Curtis, Paul Kong Thoo Lin, Woei Ping Cheng and Clare Hoskins Pages 224 - 238 ( 15 )
Polymeric micelles have received considerable interest for their use as drug delivery vehicles for hydrophobic drug solubilisation. Inorganic metallic nanoparticles have already been exploited clinically in diagnostics for their contrast ability, using magnetic resonance imaging. The combination of these two platforms results in a multifunctional drug carrier for image-guided drug delivery. Here we report the synthesis and evaluation of a new class of poly(allylamine) (PAA) polymer grafted with hydrophobic oxadiazole (Ox) pendant group in a 5% molar monomer: pendant ratio. Further, the thiol-containing pendant group facilitated the attachment of hybrid iron oxide-gold nanoparticles (HNPs) via dative covalent bonding. Physicochemical characterisation of both PAA-Ox5 and PAA-Ox5-HNP polymers was carried out using elemental analysis, nuclear magnetic resonance (NMR), fourier transform infrared spectroscopy (FTIR) and photon correlation spectroscopy (PCS). The drug loading potential of these novel aggregates was investigated, through direct conjugation of hydrophilic and encapsulation of hydrophobic drugs, respectively. The model hydrophobic drugs 2,6- diisopropylphenol (propofol) and (2S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H,4'H-spiro[1-benzofuran-2,1'- cyclohexene]-3,4'-dione (griseofulvin), and the chemotherapeutic agents bisnapthalamidopropyldiaminooctane (BNIPDaoct) and 6-Thioguanine (6-TG) were used. The data showed that the addition of HNPs onto the PAA-Ox5 structure resulted in aggregates of 175 nm in diameter. The PAA-Ox5-HNP nano-aggregates were capable of high drug solubilisation capacities (25.79 mgmL-1, 1.68 mgmL-1 and 0.92 mgmL-1) for propofol, griseofulvin and BNIPDaoct, respectively. 6-TG was also successfully conjugated into the polymer structure (2.8 mgmL-1). In vitro assays on human pancreatic adenocarcinoma cells (BxPC-3) showed increased drug uptake and decreased IC50 values using the novel formulations compared with free drug. This study highlights the potential of PAA-Ox5-HNP as a bi-functional imaging and drug delivery platform.
Amphiphilic polymer, drug solubilisation, hybrid nanoparticle, image guided drug delivery, magnetomicelle.
Institute for Science and Technology in Medicine, School of Pharmacy, Keele University, Keele, ST5 5BG, UK.