Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations

Abstract

Background: Inhaled corticosteroids provide unique systems for local treatment of asthma or chronic obstructive pulmonary disease. However, the use of poorly soluble drugs for nebulization has been inadequate, and many patients rely on large doses to achieve optimal control of their disease. Theoretically, nanotechnology with a sustained-release formulation may provide a favorable therapeutic index. The aim of this study was to determine the feasibility of using sterically stabilized phospholipid nanomicelles of budesonide for pulmonary delivery via nebulization. Methods: PEG 5000 -DSPE polymeric micelles containing budesonide (BUD-SSMs) were prepared by the coprecipitation and reconstitution method, and the physicochemical and pharmacodynamic characteristics of BUD-SSMs were investigated. Results: The optimal concentration of solubilized budesonide at 5 mM PEG 5000 -DSPE was 605.71 ± 6.38 µg/mL, with a single-sized peak population determined by photon correlation spectroscopy and a particle size distribution of 21.51 ± 1.5 nm. The zeta potential of BUD-SSMs was −28.43 ± 1.98 mV. The percent entrapment efficiency, percent yield, and percent drug loading of the lyophilized formulations were 100.13% ± 1.09%, 97.98% ± 1.95%, and 2.01% ± 0.02%, respectively. Budesonide was found to be amorphous by differential scanning calorimetry, and had no chemical interaction with PEGylated polymer according to Fourier transform infrared spectroscopy. Transmission electron microscopic images of BUD-SSMs revealed spherical nanoparticles. BUD-SSMs exhibited prolonged dissolution behavior compared with Pulmicort Respules ® (P , 0.05). Aerodynamic characteristics indicated significantly higher deposition in the lungs compared with Pulmicort Respules ® . The mass median aerodynamic, geometric standard deviation, percent emitted dose, and the fine particle fraction were 2.83 ± 0.08 µm, 2.33 ± 0.04 µm, 59.13% ± 0.19%, and 52.31% ± 0.25%, respectively. Intratracheal administration of BUD-SSMs 23 hours before challenge (1 mg/kg) in an asthmatic/chronic obstructive pulmonary disease rat model led to a significant reduction in inflammatory cell counts (76.94 ± 5.11) in bronchoalveolar lavage fluid compared with administration of Pulmicort Respules ® (25.06 ± 6.91). Conclusion:The BUD-SSMs system might be advantageous for asthma or chronic obstructive pulmonary disease and other inflammatory airway diseases.

Fasudil and SOD packaged in peptide-studded-liposomes: Properties, pharmacokinetics and ex-vivo targeting to isolated perfused rat lungs

“…Upon deposition of drug particles in the airway, drugs undergo wetting and dissolution in the airway lining fluid (Sahib et al, 2011). Water-soluble drugs can escape the clearance mechanisms (e.g.…”

Medical nanoparticles for next generation drug delivery to the lungs

“…Encouragingly, polymeric steroid nano-formulations have shown to accumulate and have higher benefits at the site of airway inflammation compared to free steroids [68]. Similarly, polymeric micelles containing budesonide were able to significantly reduce inflammatory cell counts in bronchoalveolar lavage fluid in an asthmatic/COPD rat model [69]. Another approach was reported by JOSHI and MISRA [70] who used liposomes to effectively deliver ketofin fumarate (a mast cell stabiliser known to control the inflammatory response in asthma) to the desired locations in rat lungs using dry powder inhalers [71].…”

Preparation and evaluation of inhalable itraconazole chitosan based polymeric micelles

“…Doxorubicin [15], camptothecin [16], all-trans retinoic acid [17] and paclitaxel [18] are some hydrophobic drugs that encapsulated by chitosan based polymeric micelles. There are only few reports investigating the application of inhalable polymeric micelles for delivery of all trans retinoic acid, amphotericin B and budesunide [19-21]. …”