Carbon Nanotube Membranes for Programmed Transdermal Drug Delivery

Addiction treatment is one of the most difficult health care challenges due to the mixture of complex changing neurochemical pathways and psychological behavior. A promising system would be a dosing regimen (within a doctors’ prescription limit) can be remotely programmed to account for daily environmental factors, patient input, and counselor feedback from phone interviews or internet-based surveys. Needed for this system is an ultra low power, compact, and programmable delivery device not currently available with electroporation or mechanical pumps.Membranes made of carbon nanotubes possess many advantageous attributes that include: 1) atomically flat graphite surface allows for ideal fluid slip boundary conditions 100,00 times faster than conventional pores [1] 2) the cutting process to open CNTs inherently places functional chemistry at CNT core entrance to act as chemical gatekeepers and 3) CNT are electrically conductive allowing for electrochemical reactions and application of electric fields gradients at CNT tips. Thus CNT membranes are and ideal candidate to have a voltage controlled membrane as the active element in a transdermal drug delivery device.[2] CNT membranes were functionalized with highly-charged anionic dye molecules to induce a highly efficient electroosmotic flow. The anionic charge density on CNTs was first enhanced through diazonium electrochemical modification followed by a quad-anionic dye amine functionalization. It was found that fluxes of both cationic and neutral molecules through the CNT membrane have been greatly increased under negative biases. High electro-osmotic flows of 0.05 cm/s at -300mV bias have been observed with 50% ion efficiency. This allows a 40 fold increase in pumping power efficiency compared to conventional membrane materials thereby allowing a watch battery to continuously pump for 12 days. These membranes were integrated with a nicotine formulation to obtain switchable transdermal nicotine delivery rates on human skin (in vitro) and are consistent with a Fickian diffusion in series model. The transdermal nicotine delivery device was able to successfully switch between high (1.3±0.65 µmol/hr-cm2) and low (0.33±0.22 µmol/hr-cm2) fluxes that coincide with therapeutic demand levels for nicotine cessation treatment [3]. Clonidine delivery through CNTs and human skin also matches the traditional five-day opioid withdrawal symptom treatment that requires variable delivery rates ranging from 1.7 to 5.4 nano-mole/hr.cm2.