Formulation and Pharmacokinetics of Self-Assembled Rifampicin Nanoparticle Systems for Pulmonary Delivery

Sung, Jean C.; Padilla, Danielle J.; García-Contreras, Lucila; VerBerkmoes, Jarod; Durbin, David; Peloquin, Charles A.; Elbert, Katharina J.; Hickey, Anthony; Edwards, David A.

doi:10.1007/s11095-009-9894-2

Cited by 221 publications

(92 citation statements)

References 44 publications

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“…As apparent from the figure, there was a statistical difference in plasma concentrations of ciprofloxacin when comparing the swellable particle formulation with the powder mixture formulation at all time points (p<0.05). The pharmacokinetic parameters were calculated by non-compartmental methods (39). For plasma, the areas under the curve (AUC 0-7 h ) were 2.8 and 11.6 μg h/mL for the group of swellable particles and the powder mixture group, respectively.…”

Section: Preliminary In Vivo Pharmacokinetic Studiesmentioning

confidence: 99%

Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery

El‐Sherbiny

2014

AAPS PharmSciTech

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ABSTRACT. Incorporation of drug-loaded nanoparticles into swellable and respirable microparticles is a promising strategy to avoid rapid clearance from the lung and achieve sustained drug release. In this investigation, a copolymer of polyethylene glycol grafted onto phthaloyl chitosan (PEG-g-PHCs) was synthesized and then self-assembled with ciprofloxacin to form drug-loaded nanoparticles. The nanoparticles and free drug were encapsulated into respirable and swellable alginate micro hydrogel particles and assessed as a novel system for sustained pulmonary drug delivery. Particle size, morphology, dynamic swelling profile, and in vitro drug release were investigated. Results showed that drug-loaded nanoparticles with size of 218 nm were entrapped into 3.9-μm micro hydrogel particles. The dry nano-in-micro hydrogel particles exhibited a rapid initial swelling within 2 min and showed sustained drug release. Preliminary in vivo pharmacokinetic studies were performed with formulations delivered to rats by intratracheal insufflation. Ciprofloxacin concentrations in plasma and in lung tissue and lavage were measured up to 7 h. The swellable particles showed lower ciprofloxacin levels in plasma than the controlled group (a mixture of lactose with micronized ciprofloxacin), while swellable particles achieved higher concentrations in lung tissue and lavage, indicating the swellable particles could be used for controlling drug release and prolonging lung drug concentrations.

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Section: Preliminary In Vivo Pharmacokinetic Studiesmentioning

confidence: 99%

Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery

El‐Sherbiny

2014

AAPS PharmSciTech

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“…The p values of the statistical analysis within each size group are also presented in the figure. The difference among the experimental results within each size group can be considered statistically significant for p<0.05 (29).…”

Section: Shape Factor Of the Different Shape Particlesmentioning

confidence: 99%

Effect of Particle Shape on Dry Particle Inhalation: Study of Flowability, Aerosolization, and Deposition Properties

2009

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Abstract. The shape effects of dry particles on flowability, aerosolization, and deposition properties in inhalation drug delivery are studied. The properties are compared with similar size range particles of different shapes such as sphere, needle, cube, plate, and pollen. Flowability of the particles is characterized by Carr's compressibility index and angle of slide (θ) method. The aerosolization and deposition properties of the particles are studied in vitro using an eight-stage Anderson cascade impactor with a Rotahaler®. Pollen-shaped particles are found to exhibit better flowability, higher emitted dose, and higher fine particle fraction than particles of other shapes in similar size range. They showed minimum θ of 35°and maximum emitted dose of 87% and fine particle fraction of 16%. The use of pollen-shaped particles can be a potential improvement in dry particle inhalation.

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“…Although inhalation exposure of nanomaterials would most commonly be thought of as an industrial or occupational hazard, researchers are exploring the delivery of engineered nanomaterials to the respiratory tract as a mechanism for diagnostics or targeted drug therapy. Possible biomedical applications of inhaled nanomaterials include enhanced antibiotic treatment of tuberculosis (Sung et al 2009), chemotherapy of lung cancer (El-Gendy and Berkland 2009), whole-body imaging of particles deposited in the lungs using magnetic resonance imaging (Martin et al 2008), and drug delivery to targeted regions of the lungs using magnetic fields against supramagnetic iron oxide nanoparticles (Dames et al 2007). The use of nanomaterials as a drug carrier system and the delivery of these vehicles by inhalation are a possible approach to targeting drugs to the lungs.…”

Section: Introductionmentioning

confidence: 99%

“…The use of nanomaterials as a drug carrier system and the delivery of these vehicles by inhalation are a possible approach to targeting drugs to the lungs. This therapeutic noninvasive approach would potentially offer high local drug concentrations that may lower therapeutic doses, reduce systemic effects, and reduce metabolic degradation of drugs in the liver 95 compared with oral or systemic treatment (El-Gendy and Berkland 2009;Sung et al 2009). However, in order to understand the deposition, fate, and transport of nanomaterials that enter the respiratory tract and their potential for biocompatibility or toxicity, it is critical to have a means to deliver these aerosolized materials in experimental studies in a manner comparable with that experienced in different human exposure settings (e.g., inhalation).…”

Section: Introductionmentioning

confidence: 99%

Aerosolization System for Experimental Inhalation Studies of Carbon-Based Nanomaterials

Madl

Teague²,

et al. 2012

Aerosol Science and Technology

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Assessing the human health risks associated with engineered nanomaterials is challenging because of the wide range of plausible exposure scenarios. While exposure to nanomaterials may occur through a number of pathways, inhalation is likely one of the most significant potential routes of exposure in industrial settings. An aerosolization system was developed to administer carbon nanomaterials from a dry bulk medium into airborne particles for delivery into a nose-only inhalation system. Utilization of a cannula-based feed system, diamond-coated wheel, aerosolization chamber, and krypton-85 source allows for delivery of otherwise difficult to produce respirable-sized particles. The particle size distribution (aerodynamic and actual) and morphology were characterized for different aerosolized carbon-based nanomaterials (e.g., single-walled carbon nanotubes and ultrafine carbon black). Airborne particles represented a range of size and morphological characteristics, all of which were agglomerated particles spanning in actual size from the nanosize range (<0.1 µm) to sizes greater than 5 and 10 µm for the particle's largest dimension. At a mass concentration of 1000 µg/m 3 , the size distribution as measured by the inertial impactor ranged from 1.3 to 1.7 µm with a σ g between 1.2 and 1.4 for all nanomaterial types. Because the aerodynamic size distribution is similar across different particle types, this system offers an opportunity to explore mechanisms by which different nanomaterial physicochemical characteristics impart different health effects while theoretically maintaining comparable deposition patterns in the lungs. This sys-

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Formulation and Pharmacokinetics of Self-Assembled Rifampicin Nanoparticle Systems for Pulmonary Delivery

Abstract: Our results indicate that rifampicin can be formulated into an aggregated nanoparticle form that, once delivered to animals, achieves systemic exposure and extends levels of drug in the lungs.

Cited by 221 publications

References 44 publications

Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery

Swellable Ciprofloxacin-Loaded Nano-in-Micro Hydrogel Particles for Local Lung Drug Delivery

Effect of Particle Shape on Dry Particle Inhalation: Study of Flowability, Aerosolization, and Deposition Properties

Aerosolization System for Experimental Inhalation Studies of Carbon-Based Nanomaterials

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