title: PLGA/DPPC/trimethylchitosan spray-dried microparticles for the nasal delivery of ropinirole hydrochloride: in vitro, ex vivo and cytocompatibility assessment.
abstract: In the present study we investigated polymer-lipid microparticles loaded with ropinirole hydrochloride (RH) for nasal delivery. RH microparticles were further evaluated by means of scanning electron microscopy (SEM), ζ-potential measurements, Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and x-ray diffraction (XRD). In vitro release studies were performed in simulated nasal electrolyte solution (SNES) pH5.5 at 35°C. Ex vivo permeation studies were conducted across sheep nasal mucosa. Cytocompatibility was tested in cultured human airway epithelial cells (Calu-3). SEM studies revealed spheroid microparticles in the range of 2.09μm to 2.41μm. The presence of trimethylchitosan (TMC) induced a slight shift towards less negative ζ-potential values. Surface chemistry (XPS) revealed the presence of dipalmitoylphospatidylcholine (DPPC) and poly(lactic-co-glycolic acid) (PLGA) onto microparticles' surface, further corroborating the FT-IR and XRD findings. In vitro release studies showed that the microparticle composition can partly modulate the release of RH. Ex vivo studies demonstrated a 2.35-folded enhancement of RH permeation when RH was co-formulated with TMC of low molecular weight, compared to the control. All formulations tested were found to be non-toxic to cells. The results suggest that polymer-lipid microparticles may be a promising carrier for the nasal delivery of RH.
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, Aristotle University of Thessaloniki, 54124, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Karavasili
authors.affiliation: Department of Materials Science, University of Patras, 26504 Rio, Patras, Greece; Foundation for Research and Technology, Hellas-Institute of Chemical Engineering and High Temperature, P.O. Box 1414, 26504 Patras, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Bouropoulos
authors.affiliation: Foundation for Research and Technology, Hellas-Institute of Chemical Engineering and High Temperature, P.O. Box 1414, 26504 Patras, Greece.
authors.forename: Lamprini
authors.initials: L
authors.lastname: Sygellou
authors.affiliation: Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
authors.forename: Elsa P
authors.initials: EP
authors.lastname: Amanatiadou
authors.affiliation: Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
authors.forename: Ioannis S
authors.initials: IS
authors.lastname: Vizirianakis
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmacy, Aristotle University of Thessaloniki, 54124, Greece. Electronic address: dfatouro@pharm.auth.gr.
authors.forename: Dimitrios G
authors.initials: DG
authors.lastname: Fatouros
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry* / Q000633:toxicity; D000281:Administration, Intranasal; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000737:chemistry*; D009297:Nasal Mucosa / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012756:Sheep
chemical_list: D000978:Antiparkinson Agents; D004337:Drug Carriers; D007211:Indoles; C118071:N-trimethyl chitosan chloride; C046649:ropinirole; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D015060:1,2-Dipalmitoylphosphatidylcholine; D019344:Lactic Acid; D048271:Chitosan
keywords: Calu-3 cell line; Ex vivo permeation; Hybrid microparticles; Nasal delivery; Parkinson disease; Spray drying