Development of highly porous large PLGA microparticles for pulmonary drug delivery

Yang, Yan; Bajaj, Nimisha; Xu, Pao; Ohn, Kimberly; Tsifansky, Michael D.; Yeo, Yoon

doi:10.1016/j.biomaterials.2008.12.044

Cited by 238 publications

(171 citation statements)

References 32 publications

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“…[1][2][3][4] Furthermore, the presence of drug at the site of pathology with minimal systemic absorption leads to decreased side effects. 5 Inhalation aerosols enable therapeutic effects to be achieved at much lower drug doses compared to other routes of administration offering inherently longer residence time in the lungs, which can reduce dosing frequency and increase patient compliance.…”

Section: Introductionmentioning

confidence: 99%

“…54,55 While not all of these submit your manuscript | www. aerosol performance parameters are often reported, FPF% values for porous poly(lactic-co-glycolic acid) particles were reported to be in the range of 10.7%-33.8% 5 and sodium alendronate from 34.4% to 62.0%. 38 The novel findings reported here indicate the significant potential of these lipopolymeric lung surfactant-mimic particles to be utilized to effectively deliver many different types of therapeutics to the lung as inhaled dry powder nanomedicine aerosols.…”

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confidence: 99%

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Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

Meenach¹,

Vogt²,

Anderson³

et al. 2013

IJN

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Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/ nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan ® software and were determined to be 600 nm to 1.2 µm in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and confocal Raman microscopy (CRM), and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™) coupled with the HandiHaler ® dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 µm with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the spray-drying process had a significant effect on the solid-state particle properties and that a higher pump rate produced the most optimal system. Advanced dry powder inhalers of inhalable lipopolymers for targeted dry powder inhalation delivery were successfully achieved. Dovepresssubmit your manuscript | www.dovepress.com

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

Meenach¹,

Vogt²,

Anderson³

et al. 2013

IJN

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“…Nevertheless, the aerodynamic diameter of microparticle was determined to be 8.31±1.33 µm (,10 µm), which meant that it could achieve the goal of alveolar deposition if well aerosolized and properly inhaled. 16,19,24 In addition, the porous microparticles exhibited a negative zeta potential of -14.9±4.7 mV. Through HPLC analysis, drug loading and encapsulation efficiency of disulfiram were determined to be 4.09%±0.11% and 81.84%±2.35%, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…[16][17][18] Biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), have been widely used in the construction of porous microparticles for delivering many types of drugs to lungs, such as small molecules, proteins, plasmid DNA, and oligonucleotides. [19][20][21][22][23][24][25][26] Herein, disulfiram-loaded porous PLGA microparticle was prepared through the emulsion solvent evaporation method, in which ammonium bicarbonate was used as a porogen. The antiproliferation and antimigration efficacy of porous PLGA microparticle against NSCLC cell line, A549 and HCC827, was then systematically evaluated to get a deeper insight into the mechanism.…”

Section: Introductionmentioning

confidence: 99%

Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer

Wang¹,

Yang²,

Han³

et al. 2017

IJN

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In this study, poly(lactic- co -glycolic acid) (PLGA) was used as a carrier to construct disulfiram-loaded porous microparticle through the emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. The microparticle possessed highly porous surface, suitable aerodynamic diameter for inhalation (8.31±1.33 µm), favorable drug loading (4.09%±0.11%), and sustained release profile. The antiproliferation effect of release supernatant was detected through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using non-small-cell lung cancer A549 as a model, with only 13.3% of cell viability observed for the release supernatant at 7 days. The antiproliferation mechanism was elucidated to be associated with the enhanced induction of cell apoptosis and cell cycle arrest at S phase through flow cytometry and Western blotting analysis. Finally, wound healing and transwell migration assay showed that they could efficiently inhibit the cell migration. These results demonstrated that disulfiram-loaded porous PLGA microparticle could achieve favorable antitumor efficiency, implying the potential of treating non-small-cell lung cancer in a pulmonary administration.

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“…Pulmospheres ™ is an example which is made of phosphatidylcholine, the primary component of human lung surfactant . In two interesting studies, highly porous large biodegradable polymeric particles were fabricated using ammonium bicarbonate as an effervescent porogen (Ungaro et al, 2010;Yang et al, 2009). …”

Section: Large Porous Particlesmentioning

confidence: 99%

The Role of Carrier in Dry Powder Inhaler

Hamishehkar¹,

Rahimpour²,

Javadzadeh³

2012

Recent Advances in Novel Drug Carrier Systems

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Development of highly porous large PLGA microparticles for pulmonary drug delivery

Cited by 238 publications

References 32 publications

Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer

The Role of Carrier in Dry Powder Inhaler

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