A Novel Intranasal Spray Device for the Administration of Nanoparticles to Rodents

Experimental intranasal (IN) delivery of nanoparticle (NP) drug carriers is typically performed using a pipette with or without anesthesia, a technique that may be a poor simulation of practical IN administration of drug-loaded NPs in humans. Existing IN spray devices suffer from drawbacks in terms of variability in dose-control and spray duration as well as the application of nonuniform pressure fields when a NP-formulated drug is aerosolized. Furthermore, existing spray devices require large volumes that may not be available or may be prohibitively expensive to prepare. In response, we have developed a novel pneumatically driven IN spray device for the administration of NPs, which is capable of administering extremely small quantities (50–100 μl) of NP suspension in a fine spray that disperses the NPs uniformly onto the tissue. This device was validated using haloperidol-loaded Solanum tuberosum lectin (STL)-functionalized, poly(ethylene glycol)–block-poly(d,l-lactic-co-glycolic acid) (PEG–PLGA) NPs targeted for delivery to the brain for schizophrenia treatment. A pneumatic pressure of 100 kPa was found to be optimal to produce a spray that effectively aerosolizes NP suspensions and delivers them evenly to the olfactory epithelium. IN administration of STL-functionalized NPs using the IN spray device increased brain tissue haloperidol concentrations by a factor of 1.2–1.5× compared to STL-functionalized NPs administered IN with a pipette. Such improved delivery enables the use of lower drug doses and thus offers both fewer local side-effects and lower costs without compromising therapeutic efficacy.