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

Abstract

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 drugloaded NPs in humans. Existing IN spray devices suffer from drawbacks in terms of variability in dosecontrol and spray duration as well as the application of nonuniform pressure fields when a NPformulated 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 خ¼l) of NP suspension in a fine spray that disperses the NPs uniformly onto the tissue. This device was validated using haloperidolloaded Solanum tuberosum lectin (STL)functionalized, poly(ethylene glycol)–blockpoly(d,llacticcoglycolic 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 STLfunctionalized NPs using the IN spray device increased brain tissue haloperidol concentrations by a factor of 1.2–1.5أ— compared to STLfunctionalized NPs administered IN with a pipette. Such improved delivery enables the use of lower drug doses and thus offers both fewer local sideeffects and lower costs without compromising therapeutic efficacy.