In vitro and in vivo evaluation of a dry powder endotracheal insufflator device for use in dose-dependent preclinical studies in mice

Duret, Christophe; Wauthoz, Nathalie; Merlos, Romain; Goole, Jonathan; Maris, Calliope; Roland, Isabelle; Sebti, Thami; Vanderbist, Francis; Amighi, Karim

doi:10.1016/j.ejpb.2012.04.004

Cited by 45 publications

(35 citation statements)

References 14 publications

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“…The regional lung distribution in rodents using this aerosolizer has been already investigated using in vivo optical imaging. 34 However, this imaging technique has certain limitations in terms of image quantification and translation into large species or humans, due to the low penetration capacity of visible and infrared light. The SPECT-CT images acquired immediately after administration of the labeled SCPN confirmed the presence of nanoparticles over the whole lungs, although the regional distribution was not completely homogeneous (Fig.…”

Section: Equal Concentration and Dynamic Viscosity Values (Stokes-einmentioning

confidence: 99%

Synthesis and functionalization of dextran-based single-chain nanoparticles in aqueous media

et al. 2017

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Synthesis and Functionalization of Dextran-Based Single-Chain Nanoparticles in Aqueous Media IK4-CIDETEC, Pº Miramón 196, 20014, Donostia-San Sebastián, Spain. b. Radiochemistry and Nuclear Imaging Group, CIC biomaGUNE, Pº Miramón 182, 20014, Donostia-San Sebastián, Spain. Water-dispersible dextran-based single-chain polymer nanoparticles (SCPNs) were prepared in aqueous media and mild conditions. Radiolabeling of the resulting biocompatible materials allowed the study of lung deposition of aqueous aerosols after intratracheal nebulization by means of single-photon emission computed tomography (SPECT), demostrating their potential use as imaging contrast agents.Advances in engineering polymer chains at the molecular level 1 have pushed the development of synthetic strategies for the controlled compaction of single polymer coils into unimolecular soft nano-objects, named single-chain polymer nanoparticles (SCPNs).2-4 SCPNs based on synthetic polymers benefit from the possibility of a controlled construction of the precursors in order to prepare tuned SCPNs with desired size and functionality.3 Additionally, a wide variety of biocompatible, non-toxic and ready-to-use natural polymers are available. Consequently, SCPNs have gained interest as potential mimetics of biomacromolecules such as proteins 5,6 and for application in different fields including nanomedicine.7-9 Among natural polymers, polysaccharides can be envisaged as natural analogues of polyethylene glycol (PEG). For example, dextrans have been used in several biomedical applications due to aqueous solubility, biocompatibility, biodegradability, wide availability, ease of modification and non-fouling properties.10,11 However, in vivo application of SCPNs can be limited due to their small size. Rapid blood clearance is expected after intravenous administration of particles below 5 nm size. 12 In the last years, non-invasive lung administration route has been broadly studied, 13 and SCPNs could be beneficial due to their small size.14 Synthetic routes to SCPNs are mainly based on intrachain homo-and hetero-coupling or cross-linking-induced collapseof pre-functionalized polymers through covalent, dynamic covalent, and non-covalent bonding. 15,16 Most of the covalent strategies are performed in organic solvents and require highly diluted polymer solutions (usually <1 mg/mL), high temperatures and/or the presence of metal catalysts. The preparation of SCPNs through "continuous addition" avoids ultra-dilution conditions, which is beneficial for multigram scale preparations. 17 Recently, it has been described that the presence of oligo(ethylene glycol) brushes as side-chains allows to achieve SCPNs at high polymer concentrations (100 mg/mL). 18 However, the development of general procedures to obtain functionalizable SCPNs in aqueous media, mild conditions and scalable conditions is still a challenging issue.Our group reported a strategy to generate structurally defined and water-dispersible poly(methacrylic acid)-based SCPNs.19 In pursuit of novel types of...

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Section: Equal Concentration and Dynamic Viscosity Values (Stokes-einmentioning

confidence: 99%

Synthesis and functionalization of dextran-based single-chain nanoparticles in aqueous media

et al. 2017

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“…RAW 264.7 cells were used to evaluate the anti-inflammatory effects for asthma as a heterogeneous airway inflammatory disease [17]. The MTT assay was performed after the cells had been incubated with SJT extract or SJTMPs for 24 hours at concentrations equivalent to 0.01 - 3 mg/mL of SJT.…”

Section: Resultsmentioning

confidence: 99%

“…Seven days after the initial challenge, the mice were exposed to aerosolized OVA for 30 minutes per day, 3 days per week, for 8 weeks (1 mg/mL OVA in normal saline for the first 4 weeks and 2.5 mg/mL OVA in normal saline for the last 4 weeks). Specifically, the particles were introduced into the lungs through a catheter by using a PennCentuty dry-powder insufflator (Wyndmoor, PA, USA) [17]. SJT (200 and 400 mg/kg) was orally administered every day for a week during the last 2 weeks before sacrifice.…”

Section: Methodsmentioning

confidence: 99%

Effects of Inhalable Microparticles of Seonpyejeongcheon-Tang in an Asthma Mouse Model - Effects of Microparticles of SJT -

Yang

Chulhwa

Kim

et al. 2016

Journal of Pharmacopuncture

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Objectives:Allergic asthma generally presents with symptoms of wheezing, coughing, breathlessness, and airway inflammation. Seonpyejeongcheon-tang (SJT) consists of 12 herbs. It originated from Jeongcheon-tang (JT), also known as Ding-chuan-tang, composed of 7 herbs, in She-sheng-zhong-miao-fang. This study aimed to evaluate the effects of local delivery of SJT via inhalable microparticles in an asthma mouse model.Methods:Microparticles containing SJT were produced by spray-drying with leucine as an excipient. SJT microparticles were evaluated with respect to their aerodynamic properties, in vitro cytotoxicity, in vivo toxicity, and therapeutic effects on ovalbumin (OVA)-induced asthma in comparison with orally-administered SJT.Results:SJT microparticles provided desirable aerodynamic properties (fine particle fraction of 48.9% ± 6.4% and mass median aerodynamic diameter of 3.7 ± 0.3 μm). SJT microparticles did not show any cytotoxicity against RAW 264.7 macrophages at concentrations of 0.01 - 3 mg/mL. Inhaled SJT microparticles decreased the levels of IL-4, IL-5, IL-13, IL-17A, eotaxin and OVA-IgE in bronchoalveolar lavage fluid (BALF) in mice with OVA-induced asthma. These effects were verified by histological evaluation of the levels of infiltration of inflammatory cells and collagen, destructions of alveoli and bronchioles, and hyperplasia of goblet cells in lung tissues. The effects of SJT microparticles in the asthma model were equivalent to those of orally-administered SJT extract.Conclusion:This study suggests that SJT is a promising agent for inhalation therapy for patients with asthma.

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“…The control and experimental groups were administered Relenza Õ and zanamivir DPI, respectively, via an endotracheal administration. Aerosol particles generated from the DP-4 powder insufflators (Penn-Century Inc., Philadelphia, PA) (Duret et al, 2012). The endotracheal administration used a dry powder insufflator model adapted for rat endotracheal powder insufflations.…”

Section: Pulmonary Pharmacokineticsmentioning

confidence: 99%

Preparation, characterization and pulmonary pharmacokinetics of a new inhalable zanamivir dry powder

Cai

Yang²,

Xie

et al. 2015

Drug Delivery

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This work describes a new dry powder for inhalation containing zanamivir, which is less hygroscopic than Relenza®. The powders were prepared via a spray-drying technique using mannitol as the carrier. A 5(3) central composite design was used to optimize the formulations. The final optimized powders, characterized with an angle of repose 37.48°, an aerodynamic diameter of 2.346 μm and in vitro deposition of 58.54%, were obtained by using the predicted variable values. Relenza® absorbed a significant amount of water at 66%, 75% and 85% relative humidity (RH; weight changes of approximately 1.38%, 2.18% and 3.72%, respectively). In contrast, the weight change for the zanamivir dry powder inhalation (DPI) was negligible when the RH was increased to 66%. The in vivo potential for the optimized powders was studied further in rats via the endotracheal administration of an 8.4 mg/kg dose. The bioavailability was 116% relative to Relenza®. Fluorescence imaging monitored the zanamivir dry powder inhalers in rats. The results indicated that the zanamivir DPIs were effectively delivered to the lung. These results indicate that the spray-dried zanamivir DPIs were promising for pulmonary delivery.

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In vitro and in vivo evaluation of a dry powder endotracheal insufflator device for use in dose-dependent preclinical studies in mice

Cited by 45 publications

References 14 publications

Synthesis and functionalization of dextran-based single-chain nanoparticles in aqueous media

Synthesis and functionalization of dextran-based single-chain nanoparticles in aqueous media

Effects of Inhalable Microparticles of Seonpyejeongcheon-Tang in an Asthma Mouse Model - Effects of Microparticles of SJT -

Preparation, characterization and pulmonary pharmacokinetics of a new inhalable zanamivir dry powder

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