title: Aripiprazole loaded poly(caprolactone) nanoparticles: Optimization and in vivo pharmacokinetics.
abstract: In the present investigation, a Quality by Design strategy was applied for formulation and optimization of aripiprazole (APZ) loaded PCL nanoparticles (APNPs) using nanoprecipitation method keeping entrapment efficiency (%EE) and particle size (PS) as critical quality attributes. Establishment of design space was done followed by analysis of its robustness and sensitivity. Characterization of optimized APNPs was done using DSC, FT-IR, PXRD and TEM studies and was evaluated for drug release, hemocompatibility and nasal toxicity. PS, zeta potential and %EE of optimized APNPs were found to be 199.2±5.65nm, -21.4±4.6mV and 69.2±2.34% respectively. In vitro release study showed 90±2.69% drug release after 8h. Nasal toxicity study indicated safety of developed formulation for intranasal administration. APNPs administered via intranasal route facilitated the brain distribution of APZ incorporated with the AUC0→8 in rat brain approximately 2 times higher than that of APNPs administered via intravenous route. Increase in Cmax was observed which might help in dose reduction along with reduction in dose related side effects. The results of the study indicate that intranasally administered APZ loaded PCL NPs can potentially transport APZ via nose to brain and can serve as a non-invasive alternative for the delivery of APZ to brain.
authors.affiliation: Drug Delivery Research Laboratory, Centre of Relevance and Excellence in NDDS, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, India.
authors.forename: Krutika
authors.initials: K
authors.lastname: Sawant
authors.affiliation: Drug Delivery Research Laboratory, Centre of Relevance and Excellence in NDDS, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, India.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Drug Delivery Research Laboratory, Centre of Relevance and Excellence in NDDS, Pharmacy Department, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, India.
authors.forename: Sneha
authors.initials: S
authors.lastname: Patel
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D019540:Area Under Curve; D000068180:Aripiprazole / Q000737:chemistry* / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006041:Goats; D006207:Half-Life; D006461:Hemolysis / Q000187:drug effects; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D012372:ROC Curve; D051381:Rats; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D014150:Antipsychotic Agents; D004337:Drug Carriers; D011091:Polyesters; C016240:polycaprolactone; D000068180:Aripiprazole
keywords: Aripiprazole; Design space; Intranasal; Nanoprecipitation method; Poly(caprolactone); Quality by design; Schizophrenia