Conferring biodegradability to nanoparticles is vitally important when nanomedicine applications are being targeted as this prevents potential problems with bio-accumulation of by-products after delivery. In this work, dextran has been modified (and rendered hydrophobic) by partial acetalation.  A solid state NMR method was first developed to fully characterize the acetalated polymers.  In a subsequent synthetic step, RAFT functionality was attached via residual unmodified hydroxyl groups. The RAFT groups were then used in a living free radical polymerization reaction to control the growth of hydrophilic PEG-methacrylate chains, thereby generating amphiphilic comb-like polymers. The amphiphilic polymers were then self-assembled in water to form various morphologies depending on the hydrophobic/hydrophilic balance imparted by the constituent building blocks, with PEG at the periphery acting as a non-fouling biocompatible polymer layer. The versatility of the synthetic approach permitted a number of different nanoparticles to assemble including donut, worm-like rod, and micellar structures. The acetalated dextran nanoparticles were designed for potential drug delivery applications based on the premise that in the cell compartments (endosome, lysozome) the acetalated dextran would hydrolyse, destroying the nanoparticle structure releasing the encapsulated hydrophobic drug.  To demonstrate the feasibility of a drug delivery approach, doxorubicin was loaded into the hydrophobic interiors of the nanoparticles. In-vitro studies confirmed minimal cytotoxicity of the (unloaded) nanoparticles, even after 3 days, proving that the hydrolysis products from the acetal groups (methanol and acetone) had no observable cytotoxic effect. Efficient delivery of doxorubicin to a human neuroblastoma cell line (SY-5Y) was confirmed by confocal microscopy and flow cytometry. An intriguing initial result is reported that in vitro studies of doxorubicin-loaded dextran-nanoparticles (compared to free doxorubicin) revealed an increased differential toxicity towards a cancer cell line when compared to a normal cell line.

Biodegradable and acid labile dextran-based nanoparticles for doxorubicin delivery

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.