Nose to brain delivery of nanoparticles of Thyrotropin Releasing Hormone (TRH)

Nose-to-brain delivery of drugs is affected by nanoparticles (NPs) deposited on the olfactory surface and absorbed directly into the brain. Thyrotropin releasing hormone (TRH), a water soluble drug used for treating suicidal patients. Intravenous (IV) routes for the delivery of TRH leads to failure due to the enzymatic degradation of TRH in the blood. Hence, it is required to provide a potentially high IV dose of the drug to the patient that may cause severe side effects. To overcome this issue, we designed TRH loaded polymeric nanoparticles, designed specifically for the nasal drug delivery. The NPs were constituted using a hydrolytically unstable but highly biocompatible polymer, polysebacic acid (PSA). TRH loaded PSA NPs were prepared under anhydrous conditions, following the nanoprecipitation method. The size, surface charge, and morphology of the TRH loaded PSA NPs were determined using dynamic light scattering (DLS), zeta-potential, and Scanning Electron Microscopy (SEM), respectively. The drug loaded NPs were spherical and their size range ~250 nm with the maximum drug encapsulation efficiency. Concentration dependent cell toxicity studies revealed low toxicity level for the PSA NPs and the in vitro release studies reveal that there is an immediate release of the TRH in water within one hour and almost 100% of the drug is released within 12 hours.