Nebulization of biodegradable nanoparticles: impact of nebulizer technology and nanoparticle characteristics on aerosol features

Dailey, Lea Ann; Schmehl, Thomas; Gessler, Tobias; Wittmar, Matthias; Grimminger, Friedrich; Seeger, Werner; Kissel, Thomas

doi:10.1016/s0168-3659(02)00370-x

Cited by 154 publications

(77 citation statements)

References 19 publications

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“…All values for mass median aerodynamic diameter, emitted dose, fine particle fraction, percent of drug remaining in the nebulizer, and percent of drug deposited in the induction port of the BUD-SSMs were significantly superior compared with Pulmicort Respules ® due to the particle size and presence of the hydrophilic polymer (PEG) in the outer shell of the SSMs, which induced a repulsive steric interaction between the particles that could effectively decrease the overall adhesive forces, thereby allowing more efficient aerosolization and stabilizing the colloidal suspension in air. 29,61,62 The geometric standard deviation values of BUD-SSMs were significantly (P , 0.05) higher than those of the Pulmicort Respules ® due to the effect of operating the cascade impactor at ambient temperature, which affected smaller droplets more than the larger droplets generated by the nebulizer, and produced a wider spread of geometric standard deviation values, as previously reported. 63 The improved aerodynamic performance of the BUD-SSMs leads to a decrease in the therapeutic dose and a reduction in systemic side effects.…”

Section: Aerodynamic Characterizationsupporting

confidence: 76%

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

Sahib¹,

Darwis²,

Peh³

et al. 2011

IJN

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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.

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Section: Aerodynamic Characterizationsupporting

confidence: 76%

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

Sahib¹,

Darwis²,

Peh³

et al. 2011

IJN

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“…The shorter transgene expression may result from the interactions with the tissue, as the high MW PLG microspheres were found to aggregate to a greater extent than the low MW PLG. PLG particle aggregation has been previously reported and is a function of size [38] and surface hydrophobicity [39,40]. Polymer degradation generally decreases the hydrophobicity [41], thus the faster degrading polymers would be less likely to aggregate.…”

Section: Discussionmentioning

confidence: 80%

Intramuscular delivery of DNA releasing microspheres: Microsphere properties and transgene expression

Jang

Shea²

2006

Journal of Controlled Release

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Plasmid-loaded microspheres can provide localized and sustained release into the target tissue, and thus have the potential to enhance the efficiency of naked DNA at promoting transgene expression. In this report, microsphere design parameters are investigated by correlating the extent and duration of transgene expression intramuscularly to the polymer molecular weight and the mass of DNA delivered. Plasmid DNA was incorporated into poly (lactide-co-glycolide) microspheres using a cryogenic double emulsion process, and microspheres were injected intramuscularly. Bolus injection of naked plasmid was used for control, which exhibited transfection of muscle cells with transgene expression that gradually decreased over time. Microspheres fabricated from low molecular weight polymer had expression levels that increased from day 1 to day 92, which subsequently decreased through day 174. Decreasing the microsphere mass delivered resulted in steady expression during the same time. However, microspheres fabricated with high molecular weight polymer had expression for only 14 days. Intramuscular injection resulted in a foreign body response to the microspheres, and these infiltrating cells adjacent were primarily transfected. This understanding of microsphere properties that determine transgene expression and the distribution of transfected cells may facilitate their application to fields such as tissue engineering or DNA vaccines.

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“…Several previous studies have shown that the aerosolization of colloidal systems would enhance their aggregation which is dependent on the nebulizer design. No specific correlation was found between the initial size and the size of the nebulized droplets [43,44]. For instance, the mass median diameters of aerosols generated upon nebulization were 2 to 14.4 folds larger than primary geometric particle diameters [45].…”

Section: Loading Of Vitamin E Into Liposomesmentioning

confidence: 99%

Preparation of liposomes: a novel application of microengineered membranes - investigation of the process parameters and application to the encapsulation of vitamin E

et al. 2013

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Liposomes with a mean size of 59-308 nm suitable for pulmonary drug delivery were prepared by the ethanol injection method using nickel microengineered flat disc membranes with a uniform pore size of 5-40 mm and a pore spacing of 80 or 200 mm. An ethanolic phase containing 20-50 mg ml 21 phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or Lipoid1 E80), 5-12.5 mg ml 21 stabilizer (cholesterol, stearic acid or cocoa butter), and 0 or 5 mg ml 21 vitamin E was injected through the membrane into an agitated aqueous phase at a controlled flux of 142-355 l m 22 h 21 and a shear stress on the membrane surface of 0.80-16 Pa. The mean particle size obtained under optimal conditions was 84 and 59 nm for Lipoid E80 and POPC liposomes, respectively. The particle size of the prepared liposomes increased with an increase in the pore size of the membrane and decreased with an increase in the pore spacing. Lipoid E80 liposomes stabilized by cholesterol or stearic acid maintained their initial size within 3 months. A high entrapment efficiency of 99.87% was achieved when Lipoid E80 liposomes were loaded with vitamin E. Transmission electron microscopy images revealed spherical multi-lamellar structure of vesicles. The reproducibility of the developed fabrication method was high.

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Nebulization of biodegradable nanoparticles: impact of nebulizer technology and nanoparticle characteristics on aerosol features

Cited by 154 publications

References 19 publications

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

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

Intramuscular delivery of DNA releasing microspheres: Microsphere properties and transgene expression

Preparation of liposomes: a novel application of microengineered membranes - investigation of the process parameters and application to the encapsulation of vitamin E

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