title: Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain.
abstract: OBJECTIVE
  Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined.
  
  
  METHODS
  Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing.
  
  
  RESULTS
  Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices.
  
  
  CONCLUSIONS
  Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully delivered to different brain regions shortly after intranasal administration suggesting their potential as a delivery system for Alzheimer's disease management.
authors.affiliation: a Department of Pharmaceutics and Drug manufacturing , Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria (PUA) , Alexandria , Egypt and.
authors.forename: Amira S
authors.initials: AS
authors.lastname: Hanafy
authors.affiliation: a Department of Pharmaceutics and Drug manufacturing , Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria (PUA) , Alexandria , Egypt and.
authors.forename: Ragwa M
authors.initials: RM
authors.lastname: Farid
authors.affiliation: b Department of Pharmaceutics , Faculty of Pharmacy, University of Alexandria , Alexandria , Egypt.
authors.forename: Safaa S
authors.initials: SS
authors.lastname: ElGamal
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002412:Cations; D019468:Disease Management; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
chemical_list: D002412:Cations; D004337:Drug Carriers
keywords: Alzheimer’s disease; brain delivery; chitosan nanoparticles; complexation; galantamine; intranasal route