Formation of Protein Nano-Matrix Particles with Controlled Surface Architecture for Respiratory Drug Delivery

Kwok, Philip Chi Lip; Tunsirikongkon, Amolnat; Glover, William; Chan, Hak‐Kim

doi:10.1007/s11095-010-0332-2

Cited by 33 publications

(8 citation statements)

References 34 publications

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“…Co-drying nanoparticles with excipients lead to the formation of inhalable nanoparticle aggregates in an excipient matrix [201][202][203] . Azarmi et al used spray-freeze-dried doxorubicin nanoparticles with lactose to produce particles with an aerodynamic diameter of ~3 µm [204] .…”

Section: Enlargement By Co-drying With Carrier/excipient Nanoparticlementioning

confidence: 99%

Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities

et al. 2017

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Lung cancer is the second most prevalent and the deadliest among all cancer types. Chemotherapy is recommended for lung cancers to control tumor growth and to prolong patient survival. Systemic chemotherapy typically has very limited efficacy as well as severe systemic adverse effects, which are often attributed to the distribution of anticancer drugs to non-targeted sites. In contrast, inhalation routes permit the delivery of drugs directly to the lungs providing high local concentrations that may enhance the anti-tumor effect while alleviating systemic adverse effects. Preliminary studies in animals and humans have suggested that most inhaled chemotherapies are tolerable with manageable pulmonary adverse effects, including cough and bronchospasm. Promoting the deposition of anticancer drugs in tumorous cells and minimizing access to healthy lung cells can further augment the efficacy and reduce the risk of local toxicities caused by inhaled chemotherapy. Sustained release and tumor localization characteristics make nanoparticle formulations a promising candidate for the inhaled delivery of chemotherapeutic agents against lung cancers. However, the physiology of respiratory tracts and lung clearance mechanisms present key barriers for the effective deposition and retention of inhaled nanoparticle formulations in the lungs. Recent research has focused on the development of novel formulations to maximize lung deposition and to minimize pulmonary clearance of inhaled nanoparticles. This article systematically reviews the challenges and opportunities for the pulmonary delivery of nanoparticle formulations for the treatment of lung cancers.

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Section: Enlargement By Co-drying With Carrier/excipient Nanoparticlementioning

confidence: 99%

Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities

et al. 2017

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“…leucine) (14,15), development of porous particles (i.e. Pulmosphere® technology) and formation of nanomatrix particles (16,17) can also be combined with spray drying to achieve superior formulation performance.…”

Section: Introductionmentioning

confidence: 99%

Effects of Surface Composition on the Aerosolisation and Dissolution of Inhaled Antibiotic Combination Powders Consisting of Colistin and Rifampicin

Wang

Zhou

Sun

et al. 2015

AAPS J

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Colistin is often the only effective antibiotic against the respiratory infections caused by multidrug-resistant Gram-negative bacteria. However, colistin-resistant multidrug-resistant isolates have been increasingly reported and combination therapy is preferred to combat resistance. In this study, five combination formulations containing colistin (COL) and rifampicin (RIF) were prepared by spray drying. The lowest minimum inhibitory concentration (MIC) value against Pseudomonas aeruginosa PAO1 was measured for the formulation of COL/RIF = 4:1 with relatively high emitted doses (over 80%) and satisfactory fine particle fractions (over 60%). Data from X-ray photoelectron spectroscopy (XPS) and nano-time-of-flight secondary ion mass spectrometry (ToF-SIMS) showed the surfaces of particles were mainly covered by rifampicin even for the formulation with a mass ratio of COL/RIF = 4:1. Because colistin is hygroscopic and rifampicin is hydrophobic, moisture absorption of combination formulations was significantly lower than the pure colistin formulation in the dynamic vapour sorption results. To investigate the dissolution characteristics, four dissolution test methods (diffusion Franz cell, modified Franz cell, flow-through and beaker methods) were employed and compared. The modified Franz cell method was selected to test the dissolution behaviour of aerosolised powder formulations to eliminate the effect of membrane on dissolution. The results showed that surface enrichment of hydrophobic rifampicin neither affected aerosolisation nor retarded dissolution rate of colistin in the combination formulations. For the first time, advanced surface characterisation techniques of XPS and ToF-SIMS have shown their capability to understand the effect of surface composition on the aerosolisation and dissolution of combination powders.

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“…To improve performance, particles can be formulated as "interactive mixtures", in which nanoparticles can attach to the surfaces of larger carriers [70,71]. Co-drying nanoparticles with excipients can produce inhalable nanoparticle aggregates in an excipient matrix [72][73][74]. L-leucine is a widely recognized force-control mediator that can decrease inter-particle cohesion and enhance the dispersibility of nanoparticles [75,76].…”

Section: Aerosolization and Storage Of Nanoparticlesmentioning

confidence: 99%

Pharmacokinetics of inhaled nanotherapeutics for pulmonary delivery

Shen

Minko²

2020

Journal of Controlled Release

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Pulmonary delivery of lipid-based nanotherapeutics by inhalation presents an advantageous alternative to oral and intravenous routes of administration that avoids enzymatic degradation in gastrointestinal tract and hepatic first pass metabolism and also limits off-target adverse side effects upon heathy tissues. For lung-related indications, inhalation provides localized delivery in order to enhance therapeutic efficacy at the site of action. Optimization of physicochemical properties, selected drug and inhalation format can greatly influence the pharmacokinetic behavior of inhaled nanoparticle systems and their payloads. The present review analyzes a wide range of nanoparticle systems, their formulations and consequent effect on pharmacokinetic distribution of delivered active components after inhalation.

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Formation of Protein Nano-Matrix Particles with Controlled Surface Architecture for Respiratory Drug Delivery

Abstract: Nano-matrix particles with controlled surface architecture were successfully produced by spray-drying nanosuspensions. Aerosol performance was enhanced with increasing surface roughness due to the reduction in cohesion forces.

Cited by 33 publications

References 34 publications

Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities

Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities

Effects of Surface Composition on the Aerosolisation and Dissolution of Inhaled Antibiotic Combination Powders Consisting of Colistin and Rifampicin

Pharmacokinetics of inhaled nanotherapeutics for pulmonary delivery

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