Abstract
BackgroundThis study evaluated the potential of chitosan based polymeric micelles as a nanocarrier system for pulmonary delivery of itraconazole (ITRA).MethodsHydrophobically modified chitosan were synthesized by conjugation of stearic acid to the hydrophilic depolymerized chitosan. FTIR and 1HNMR were used to prove the chemical structure and physical properties of the depolymerized and the stearic acid grafted chitosan. ITRA was entrapped into the micelles and physicochemical properties of the micelles were investigated. Fluorescence spectroscopy, dynamic laser light scattering and transmission electron microscopy were used to characterize the physicochemical properties of the prepared micelles. The in vitro pulmonary profile of polymeric micelles was studied by an air-jet nebulizer connected to a twin stage impinger.ResultsThe polymeric micelles prepared in this study could entrap up to 43.2±2.27 μg of ITRA per milliliter. All micelles showed mean diameter between 120–200 nm. The critical micelle concentration of the stearic acid grafted chitosan was found to be 1.58×10-2 mg/ml. The nebulization efficiency was up to 89% and the fine particle fraction (FPF) varied from 38% to 47%. The micelles had enough stability to remain encapsulation of the drug during nebulization process.ConclusionsIn vitro data showed that stearic acid grafted chitosan based polymeric micelles has a potential to be used as nanocarriers for delivery of itraconazole through inhalation.
Highlights
Obesity has reached epidemic proportions and is still escalating at an alarming rate worldwide
Obesity is associated with chronic activation of low-grade inflammation [3], which is implicated in the pathogenesis of obesity-associated diseases including insulin resistance, type-2 diabetes (T2D) [4, 5] and cardiovascular disease [6, 7]
A numerous of studies has been shown that shortchain fatty acids (SCFAs) inhibit inflammation with focus on butyrate and to a lesser extent on acetate and Propionic Acid (PA), [16]
Summary
Obesity has reached epidemic proportions and is still escalating at an alarming rate worldwide. In Palestine the prevalence of obesity has been shown to be approximately 4. The etiology of obesity and low-grade inflammation is complex and involves intrinsic and extrinsic factors. The colonization of germ-free mice with microbiota derived from obese mice results in significantly greater adiposity than colonization with microbiota from lean mice [12]. Prebiotic diets such as fructans [13] are associated with general better health, including the decrease in body weight, fat mass and the severity of T2D [14,15,16]. The factors that influence the composition and metabolism of intestinal
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