(20a) On-Demand Drug Delivery from Polymeric Implants Externally Triggered by near-Infrared Radiation

Traditionally, drug administration occurs either orally or intravenously, initially resulting in a high drug level inside the body, followed by a steady decrease over time. As soon as the drug level drops below the minimum therapeutic level, a new dose is required. In addition, oral drug delivery entails systemic administration, thus subjecting not only the target area, but the whole body to the drug. These two disadvantages have led to a vast amount of research on controlled release and drug targetting systems. The objective of this research is to develop an implant capable of releasing drugs on-demand using an external trigger.

Drug release can be switched on and off using the glass transition temperature (Tg) of a polymeric implant. Below this temperature, polymers are in a glassy state resulting in a slow diffusion of active compounds inside the matrix. At temperatures higher than Tg, the rubbery state of the polymer allows fast diffusion of solutes, in the range of four to six orders of magnitude faster than in the glassy state. Release based on this Tg-switch has been demonstrated previously using therapeutic ultrasound. [1]

In this study, photothermal heating induces drug release from a polymer matrix. [2] The human body is relatively transparent in the region of 700-1100 nm (therapeutic window), in which absorption by water and tissue chromophores is relatively low. [3] Introduction of a near-infrared dye into a polymer matrix, otherwise transparent to near-infrared radiation (NIR), leads to selective absorption of this radiation by the polymeric implant, resulting in drug release. The dye, a quaterrylenebis(dicarboximide) derivative (QBDC), can be incorporated into the polymer by traditional methods, such as extrusion or solvent casting.

Using a fiber coupled CW-laser (lmax: 785 nm; NA: 0.22; Pmax: 750 mW), laser-induced heat transfer inside a QBDC-doped poly(methyl methacrylate) matrix is studied experimentally as well as modeled using the finite element method (FEM). Mass transfer inside a poly(butyl methacrylate-co-methyl methacrylate) matrix with a Tg around 45°C has similarly been incorporated into the model and correlated to the release of ibuprofen in vitro. The model takes into account exponential NIR absorption, a solute concentration dependent Tg as well as a temperature dependent diffusion coefficient and heat capacity. The modeling and experimental results appear to be in good agreement.

REFERENCES

[1]      H. Bruinewoud, ?Ultrasound-Induced Drug Release from Polymer Matrices?, PhD-thesis, Technische Universiteit Eindhoven: Eindhoven, 2005

[2]      M.A.M.E. Vertommen, D.T.A. van Asseldonk, M.F. Kemmere, and J.T.F. Keurentjes, ?Drug delivery device comprising a pharmaceutically or biologically active component and an infrared absorbing compound?, US Patent application, P6009250, 2006

[3]      T. Vo-Dinh (ed.), Biomedical Photonics Handbook, CRC Press LLC, 2003