Proper treatment of drug addiction and abuse is critically important since it is estimated that the total overall costs of substance abuse in the United States exceed half a trillion dollars annually as reported by National Institute on Drug Abuse (NIDA). Compared to syringe injection and oral drug delivery, transdermal patches possess many advantages, including reduction in pain & bioharzadous waste, sustained drug delivery, low cost and self-administration. Conventional transdermal patches can provide a constant flux of drug in an easy and non‐invasive way. However many drug abuse and addiction treatments, such as nicotine, fentanyl and clonidine, require variable rates of transdermal delivery. Recently, many research efforts have been focused on carbon nanotube (CNTs) membranes, which possess many advantageous and unique attributes that include: 1) atomically flat graphite surface allows for ideal fluid slip boundary conditions 100,00 times faster than conventional pores 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 an ideal candidate as a rate-controlling component in a transdermal drug delivery device. 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 an efficient 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 15% ion efficiency. Electro-osmosis within CNT membranes is strongly related to electric field strength, ionic strength and surface charge density. Employing this phenomenon, 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. Applying the same phenomenon, the transdermal clonidine delivery rate can be enhanced from 1.6 nano-moles/hr.cm2) under 0 mV bias to 8.1 nano-moles/hr.cm2) under -600 mV bias. The traditional five‐day opioid withdrawal symptom treatment requires variable clonidine delivery rates ranging from 1.7 to 5.4 nano-mole/hr.cm2). It is notable that slower transdermal clonidine delivery rates can be easily obtained applying smaller biases. The CNT membrane acted as the rate-limiting component and observed flux values are consistent with a simple diffusion in series model that is based on Fick's law. For a 10 cm2) (commercially available size) clonidine transdermal patch made of a CNT membrane, a button cell battery with a capacity of 247 mWh can be pumping continuously for ~30 days, while the same button cell battery can work continuously for 12 days using a 25 cm2) nicotine transdermal patch made of a CNT membrane. These highly energy efficient programmable devices with minimal skin irritation and no skin barrier disruption would open an avenue for single application long-wear patches for therapies that require variable or programmable delivery rates.
- Carbon Nanotube Membranes,
Available at: http://works.bepress.com/ji_wu/13/