title: Formulation and optimization of polymeric nanoparticles for intranasal delivery of lorazepam using Box-Behnken design: in vitro and in vivo evaluation.
abstract: The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167-318 d·nm, PDI below 0.441, and -18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of 21.7 ± 1.3% with prolonged drug release of 69.5 ± 0.8% from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway.
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, Uttar Pradesh 201307, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, Uttar Pradesh 201307, India.
authors.forename: Dipika
authors.initials: D
authors.lastname: Maheshwari
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, Uttar Pradesh 201307, India.
authors.forename: Gilphy
authors.identifier: 0000-0003-1299-8990
authors.initials: G
authors.lastname: Philip
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, Uttar Pradesh 201307, India.
authors.forename: Ravish
authors.initials: R
authors.lastname: Rana
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, Uttar Pradesh 201307, India.
authors.forename: Shanu
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, Uttar Pradesh 201307, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, Uttar Pradesh 201307, India.
authors.forename: Reema
authors.initials: R
authors.lastname: Gabrani
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, Uttar Pradesh 201307, India.
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Sharma
authors.affiliation: Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
authors.forename: Javed
authors.initials: J
authors.lastname: Ali
authors.affiliation: Division of CBRN Defense, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Marg, Delhi 110054, India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Sharma
authors.affiliation: Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sector 62, Noida, Uttar Pradesh 201307, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Dang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009297:Nasal Mucosa / Q000187:drug effects; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D012756:Sheep; D013226:Status Epilepticus / Q000188:drug therapy* / Q000473:pathology; D014018:Tissue Distribution
chemical_list: D011108:Polymers; D008140:Lorazepam