Realization of polyaspartamide-based nanoparticles and in vivo lung biodistribution evaluation of a loaded glucocorticoid after aerosolization in mice

Craparo, EF; Gioia, Sante Di; Trapani, Adriana; Cellamare, Saverio; Belgiovine, Giuliana; Mandracchia, Delia; Giammona, Gaetano; Cavallaro, Gennara; Conese, Massimo

doi:10.1016/j.ijpharm.2016.06.042

Cited by 9 publications

(9 citation statements)

References 39 publications

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“…PHEA is a biocompatible water-soluble polyaminoacidic polymer, whose derivatives have been largely used for tissue engineering − and drug- and gene-delivery applications, ,,,, with a recent focus for pulmonary drug delivery. − Moreover, PHEA presents one −OH group for each repetitive unit, making it suitable for controlled, highly repeatable, and scalable derivatization synthesis.…”

Section: Resultsmentioning

confidence: 99%

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Mucus and Cell-Penetrating Nanoparticles Embedded in Nano-into-Micro Formulations for Pulmonary Delivery of Ivacaftor in Patients with Cystic Fibrosis

Porsio

Craparo

Mauro

et al. 2017

ACS Appl. Mater. Interfaces

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Here, mucus-penetrating nanoparticles (NPs) for pulmonary administration of ivacaftor in patients with cystic fibrosis (CF) were produced with the dual aim of enhancing ivacaftor delivery to the airway epithelial cells, by rapid diffusion through the mucus barrier, and at the same time, promoting ivacaftor lung cellular uptake. Pegylated and Tat-decorated fluorescent nanoparticles (FNPs) were produced by nanoprecipitation, starting from two synthetic copolymers, and showed nanometric sizes (∼70 nm), a slightly negative ζ potential, and high cytocompatibility toward human bronchial epithelium cells. After having showed the significant presence of poly(ethylene glycol) chains and Tat protein onto the FNP surface, the FNP mucus-penetrating ability, ivacaftor release profile, and lung cellular uptake were studied in the presence of CF-artificial mucus as a function of the FNP surface chemical composition. Moreover, microparticle-based pulmonary drug-delivery systems composed of mucus-penetrating FNPs loaded with ivacaftor and mannitol were prepared by using the nano-into-micro strategy and realized by spray-drying, thereby providing optimal preservation and stabilization of FNP technological and fluorescence properties.

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Section: Resultsmentioning

confidence: 99%

“…For this reason, two different copolymers were synthesized starting from α,β-poly( N -2-hydroxyethyl)- d , l -aspartamide (PHEA), , a biocompatible water-soluble polyaminoacidic polymer, whose derivatives have been largely used for drug- and gene-delivery applications, − with a recent focus for pulmonary delivery. − …”

Section: Introductionmentioning

confidence: 99%

Mucus and Cell-Penetrating Nanoparticles Embedded in Nano-into-Micro Formulations for Pulmonary Delivery of Ivacaftor in Patients with Cystic Fibrosis

Porsio

Craparo

Mauro

et al. 2017

ACS Appl. Mater. Interfaces

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“…Indeed, the capability to counteract this CSE-mediated effect was not found for free FP. This effect on survivin expression could be explained considering the enhancement of FP uptake and internalization in 16-HBE exposed to CSE when it is entrapped into our polymeric carriers, that interact with cell membrane and could promote the uptake of encapsulated drug via NPs endocytosis and/or drug diffusion [ 9 , 13 ].…”

Section: Resultsmentioning

confidence: 99%

“…High-pressure homogenization (HPH) was used as procedure to obtain PHEA-PLA-PEG 2000 based nanoparticles (NPs) [ 13 ]. Based on this method, a PHEA-PLA-PEG 2000 dispersion in dichloromethane at a concentration of 16.7 mg/mL (6 mL) was used as organic phase and mixed by stirring at 20,500 rpm with an aqueous phase (50 mL) containing Pluronic F68 (15 mg).…”

Section: Methodsmentioning

confidence: 99%

“…The applied method to obtain these particles was high-pressure homogenization (HPH), which contemplates as a final step organic solvent evaporation, while the starting material was a pegylated-polylactide graft copolymer of α,β-poly( N -2-hydroxyethyl)- d , l -aspartamide (PHEA), recently synthesized by our group and named PHEA-PLA-PEG 2000 [ 10 , 11 ]. The suitability of the latter to realize biocompatible and either stealth or mucus-penetrating polymeric NPs was already described in the literature [ 12 , 13 ]. Here, the suitability of these particles to be used as carriers for pulmonary administration of FP was investigated by carrying out a proper chemical-physical and technological characterization of the obtained drug-loaded NPs.…”

Section: Introductionmentioning

confidence: 99%

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Polyaspartamide-Based Nanoparticles Loaded with Fluticasone Propionate and the In Vitro Evaluation towards Cigarette Smoke Effects

et al. 2017

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This paper describes the evaluation of polymeric nanoparticles (NPs) as a potential carrier for lung administration of fluticasone propionate (FP). The chosen polymeric material to produce NPs was a copolymer based on α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) whose backbone was derivatised with different molecules, such as poly(lactic acid) (PLA) and polyethylenglycol (PEG). The chosen method to produce NPs from PHEA-PLA-PEG2000 was the method based on high-pressure homogenization and subsequent solvent evaporation by adding Pluronic F68 during the process and trehalose before lyophilisation. Obtained colloidal FP-loaded NPs showed a slightly negative surface charge and nanometric dimensions that are maintained after storage for one year at −20 °C and 5 °C. The FP loading was about 2.9 wt % and the drug was slowly released in simulated lung fluid. Moreover, the obtained NPs, containing the drug or not, were biocompatible and did not induce cell necrosis and cell apoptosis on bronchial epithelial cells (16-HBE). Further in vitro testing on cigarette smoke extract (CSE)-stimulated 16-HBE revealed that FP-loaded NPs were able to reduce the survivin expression, while either free FP or empty NPs were not able to significantly reduce this effect.

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Polymeric drug delivery micelle-like nanocarriers for pulmonary administration of beclomethasone dipropionate

Triolo

Craparo

Porsio

et al. 2017

Colloids and Surfaces B: Biointerfaces

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Realization of polyaspartamide-based nanoparticles and in vivo lung biodistribution evaluation of a loaded glucocorticoid after aerosolization in mice

Cited by 9 publications

References 39 publications

Mucus and Cell-Penetrating Nanoparticles Embedded in Nano-into-Micro Formulations for Pulmonary Delivery of Ivacaftor in Patients with Cystic Fibrosis

Mucus and Cell-Penetrating Nanoparticles Embedded in Nano-into-Micro Formulations for Pulmonary Delivery of Ivacaftor in Patients with Cystic Fibrosis

Polyaspartamide-Based Nanoparticles Loaded with Fluticasone Propionate and the In Vitro Evaluation towards Cigarette Smoke Effects

Polymeric drug delivery micelle-like nanocarriers for pulmonary administration of beclomethasone dipropionate

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