title: Intranasal delivery of cyclobenzaprine hydrochloride-loaded thiolated chitosan nanoparticles for pain relief.
abstract: The purpose of present investigation was to formulate and characterize the cyclobenzaprine HCl (CBZ)-loaded thiolated chitosan nanoparticles and assessment of in-vitro cell viability, trans-mucosal permeability on RPMI2650 cell monolayer, in-vivo pharmacokinetic and pharmacodynamic study of thiolated chitosan nanoparticles on Swiss albino mice after intranasal administration. A significant high permeation of drug was observed from thiolated chitosan nanoparticles with less toxicity on nasal epithelial cells. Brain uptake of the drug after (99m)Tc labeling was significantly enhanced after thiolation of chitosan. CBZ-loaded thiolated chitosan NPs significantly reverse the N-Methyl-.-Aspartate (NMDA)-induced hyperalgesia by intranasal administration than the CBZ solution. The studies of present investigation revealed that thiolation of chitosan significantly reduce trans-mucosal toxicity with enhanced trans-mucosal permeability via paracellular pathway and brain uptake of a hydrophilic drug (normally impermeable across blood brain barrier) and pain alleviation activity via intranasal route.
authors.affiliation: Pharmacy Department, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.
authors.forename: Deepa
authors.initials: D
authors.lastname: Patel
authors.forename: Sachin
authors.initials: S
authors.lastname: Naik
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.forename: Rashi
authors.initials: R
authors.lastname: Mathur
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
authors.forename: Ambikanandan
authors.initials: A
authors.lastname: Misra
mesh_terms: D000281:Administration, Intranasal / Q000379:methods; D000639:Amitriptyline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010146:Pain / Q000188:drug therapy*; D010539:Permeability; D014018:Tissue Distribution
chemical_list: D000639:Amitriptyline; C004704:cyclobenzaprine; D048271:Chitosan