Elucidating The Impact of Liposomal Drug Delivery in Determining The Most Efficient Drug For Addiction Treatment

An accepted theory of addiction is the 3-staged cycle of addiction consisting of intoxication, wherein the patient is actively taking the drug, withdrawal, wherein the withdrawal phase the individual is experiencing the symptoms and anxiety from parting from their addiction, and finally anticipation, where the cravings are developed. Several studies have shown that by prolonging the withdrawal phase it is possible to decrease the intensity or cause the extinction of cravings, which in turn hints at stopping the development and progression of addiction. While presently there are numerous pharmaceuticals in the market to combat cocaine addiction, many of them fail to meet the mark. The usage of liposomes, vesicles composed of predominantly lipids, cholesterol, PEG-tails, and in our study also contain a 5% internal sucrose solution, could potentially help as they are a noninvasive-safe means of neuromodulation. In applying liposomes to addiction treatment, we must first determine what drug should be encased and tested. Our study examines which of the three clinically relevant drugs in battling cocaine addiction: ketamine, ropivacaine, or clonidine, encased in a liposome, which would be most advantageous towards usage in rat models and later in clinical trials. Based on uncaging experiments and previous clinical history, ketamine appears to be the best choice for liposomal uncaging to target the withdrawal phase. The future of this work lies in applying ketamine liposomes in a cocaine addicted rat model via self-administration chambers and using ultrasound uncaging to target the prefrontal cortex, an important dopaminergic region, and using cue receptivity experiments determine if ketamine liposomes are able to prolong withdrawal and subsequently determine the rate of release.