It has recently emerged that drugs such as the mTOR inhibitor rapamycin (Rapa) may play a key role in the treatment of airway inflammation associated with lung diseases, such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis. Nevertheless, Rapa clinical application is still prevented by its unfavorable chemical-physical properties, limited oral bioavailability, and adverse effects related to non-specific biodistribution. In this paper, the design and production of a novel formulation of Rapa based on nano into micro (NiM) particles are detailed. To achieve it, Rapa-loaded nanoparticles were produced by nanoprecipitation of an amphiphilic pegylated poly-e-caprolactone/polyhydroxyethyl aspartamide graft copolymer. The obtained nanoparticles that showed a drug loading of 14.4 wt% (corresponding to an encapsulation efficiency of 82 wt%) did not interact with mucins and were able to release and protect Rapa from degradation in simulated lung and cell fluids. To allow their local administration to the lungs as a dry powder, particle engineering at micro-sized level was done by embedding nanoparticles into mannitol-based microparticles by spray drying. Obtained NiM particles had a mean diameter of about 2-mu, spherical shape and had good potential to be delivered to the lungs by a breath-activated dry powder inhalers. Rheological and turbidity experiments showed that these NiM particles can dissolve in lung simulated fluid and deliver the Rapa-loaded pegylated nanoparticles, which can diffuse through the mucus layer.

Craparo, E.F., Drago, S.E., Quaglia, F., Ungaro, F., Cavallaro, G. (2022). Development of a novel rapamycin loaded nano- into micro-formulation for treatment of lung inflammation. DRUG DELIVERY AND TRANSLATIONAL RESEARCH, 12(8), 1859-1872 [10.1007/s13346-021-01102-5].

Development of a novel rapamycin loaded nano- into micro-formulation for treatment of lung inflammation

Craparo, Emanuela Fabiola
Primo
;
Drago, Salvatore Emanuele;Cavallaro, Gennara
Ultimo
2022-02-19

Abstract

It has recently emerged that drugs such as the mTOR inhibitor rapamycin (Rapa) may play a key role in the treatment of airway inflammation associated with lung diseases, such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis. Nevertheless, Rapa clinical application is still prevented by its unfavorable chemical-physical properties, limited oral bioavailability, and adverse effects related to non-specific biodistribution. In this paper, the design and production of a novel formulation of Rapa based on nano into micro (NiM) particles are detailed. To achieve it, Rapa-loaded nanoparticles were produced by nanoprecipitation of an amphiphilic pegylated poly-e-caprolactone/polyhydroxyethyl aspartamide graft copolymer. The obtained nanoparticles that showed a drug loading of 14.4 wt% (corresponding to an encapsulation efficiency of 82 wt%) did not interact with mucins and were able to release and protect Rapa from degradation in simulated lung and cell fluids. To allow their local administration to the lungs as a dry powder, particle engineering at micro-sized level was done by embedding nanoparticles into mannitol-based microparticles by spray drying. Obtained NiM particles had a mean diameter of about 2-mu, spherical shape and had good potential to be delivered to the lungs by a breath-activated dry powder inhalers. Rheological and turbidity experiments showed that these NiM particles can dissolve in lung simulated fluid and deliver the Rapa-loaded pegylated nanoparticles, which can diffuse through the mucus layer.
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
https://link.springer.com/article/10.1007/s13346-021-01102-5
Craparo, E.F., Drago, S.E., Quaglia, F., Ungaro, F., Cavallaro, G. (2022). Development of a novel rapamycin loaded nano- into micro-formulation for treatment of lung inflammation. DRUG DELIVERY AND TRANSLATIONAL RESEARCH, 12(8), 1859-1872 [10.1007/s13346-021-01102-5].
File in questo prodotto:
File Dimensione Formato  
pubbl73_DrugDelTranslResearch2022.pdf

accesso aperto

Tipologia: Versione Editoriale
Dimensione 2.29 MB
Formato Adobe PDF
2.29 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/575170
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 3
social impact