Formulation and evaluation of aptamer-functionalized polymeric nanoparticles for targeted delivery of antidepressant drugs to the brain

In order to improve treatment efficacy and minimize systemic adverse effects, the present effort sought to create and assess aptamer-functionalized polymeric nanoparticles (AF-PNPs) for the targeted delivery of antidepressant medications to the brain. To create PLGA nanoparticles encasing the model antidepressant fluoxetine, the nanoprecipitation approach was used. Afterwards, nucleolin-specific aptamers were added to the nanoparticles by the use of carbodiimide chemistry. The improved mixture displayed a zeta potential of -26.7 ± 1.5 mV, a polydispersity index of 0.182 ± 0.02 and an average particle size of 142.6 ± 3.8 nm. The drug loading and drug encapsulation efficiency were measured at 12.3 ± 1.1% and 78.5 ± 2.4%, respectively. Experiments with in vitro release showed a biphasic pattern, with a 23% burst after 6 hours and a sustained release of up to 84% over 72 hours. In comparison to non-functionalized nanoparticles, aptamer conjugation increased cellular uptake in SH-SY5Y neuroblastoma cells by a factor of 2.3 (p < 0.01). Hemolysis tests proved hemocompatibility with a hemolysis rate of less than 2%. The brain accumulation of AF-PNPs was substantially higher (3.4 ± 0.6% ID/g tissue) four hours after injection in Wistar rats compared to non-functionalized PNPs (1.2 ± 0.3% ID/g tissue) and free drug (0.7 ± 0.2% ID/g tissue) (p < 0.001). AF-PNPs lowered immobility time by 48%, non-functionalized PNPs by 29%, and free medication by 18%, according to pharmacodynamic evaluation using the forced swim test. In order to improve treatment outcomes, decrease systemic toxicity, and increase bioavailability, the results show that aptamer-functionalized polymeric nanoparticles offer a practical and effective platform for targeted delivery of antidepressants to the brain.