title: Nicotine hydrogen tartrate loaded chitosan nanoparticles: Formulation, characterization and in vitro delivery from dry powder inhaler formulation.
abstract: This study reports the development of nanoparticles in the form of inhalable micro-aggregates of biodegradable chitosan (CS) loaded with nicotine hydrogen tartrate (NHT) for potential pulmonary delivery of nicotine from dry powder inhaler (DPI) formulations with prolonged release profile. The NHT-loaded CS particles were prepared using a water-in-oil emulsion crosslinking method. The prepared particles were characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for morphological studies; Zetasizer and Mastersizer were applied for particle size analysis. The in vitro aerosolization of the formulations was studied using a twin-stage-impinger (TSI) and promising aerosolization characteristics were shown. The nanoparticles were spherical with size ranges between 167 and 411nm while micro-aggregates (3.73-4.73μm) were formed among nanoparticles. According to differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, the NHT crystallinity was lost when in the particles, indicating it was uniformly dispersed as a solid solution. On the basis of X-ray photoelectron spectroscopy (XPS) analysis, the amount of NHT loaded on the surface of CS increased proportionally with increasing drug loading in the bulk so there was no surface enhancement. The fine particle doses (FPD) of NHT ranging between 1.7 and 3.2mg from DPI formulations were concentration dependent and increased with increased drug loading. Based on the in vitro release study, NHT released from CS particles with a burst release in the first 8h and subsequent prolonged release of nicotine.
authors.affiliation: Pharmacy Discipline, School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia; Institute of Health Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Health Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, QLD, Australia; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane, QLD, Australia.
authors.forename: Graeme
authors.initials: G
authors.lastname: George
authors.affiliation: Institute of Health Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, QLD, Australia; Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Selena
authors.initials: S
authors.lastname: Bartlett
authors.affiliation: Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China.
authors.forename: Changyou
authors.initials: C
authors.lastname: Gao
authors.affiliation: Pharmacy Discipline, School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia; Institute of Health Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, QLD, Australia. Electronic address: nazrul.islam@qut.edu.au.
authors.forename: Nazrul
authors.initials: N
authors.lastname: Islam
mesh_terms: D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry*; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009538:Nicotine / Q000008:administration & dosage*; D056951:Photoelectron Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D009538:Nicotine; D048271:Chitosan