Implantable Biomems Devices for Localized Breast Cancer Drug Delivery

Abstract

Implantable Bio-Micro-Electro-Mechanical Systems (BioMEMS) represent a new class of devices that can provide localized cancer drug delivery by the combined effect of chemotherapy and hyperthermia which gives it an advantage over prior devices. The current work presents the results of a theoretical and experimental study of a novel implantable drug delivery device. Prototype Poly-di-methyl-siloxane (PDMS) packages with well-controlled micro-channels, and a drug storage compartments were fabricated along with a drug storing polymer produced by free radical polymerization of Poly(N-isopropylacrylamide)(PNIPA), comonomers of Acrylamide (AM). The swelling due to the uptake of water, bromophenol blue and a bacterial extract prodigiosin (an apoptotic agent), were studied using weight gain experiments conducted over temperatures within the range in which hyperthermia (28- 48oC) could occur during drug delivery. These studies provided understanding of the underlying mechanisms of diffusion and swelling of these PNIPA-based gels. The results show that drug release may be well described by monolithic and membrane diffusion models. The in-vitro studies at 43 ̊C indicate that a lesser amount of drug delivery is achieved when the delivery is accompanied with heat. Morphological studies with an environmental Scanning Electron Microscope (SEM) reveal a polymeric network of the PNIPA-based gels. The diffusion coefficients obtained varied from 2.10 x10 -12 m2/s at 28 ̊C to 4.8162x10-6 m2/s at 48 ̊C. The results obtained from the released exponent as well as the diffusion coefficient from the gels were consistent to prior work [1- 3]. Prior work [2] indicated diffusion coefficients of PNIPA which were found to be within 0.2 x 10-12 m2/s and 4 x 10-12 m2/s, which was said to be dependent on the network densities of the gels. Recent work [1] also revealed diffusion coefficient for PNIPA within 1.68x10 -12 m2/s at 37 ̊C to 1.12x10 -6 m2/s at 45 ̊C. The release exponents indicated a domination of non-Fickian diffusion.