Feasibility Study of Mesoporous Silica Particles for Pulmonary Drug Delivery: Therapeutic Treatment with Dexamethasone in a Mouse Model of Airway Inflammation

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Gulin-Sarfraz T, Jonasson S, Wigenstam E, von Haartman E, Bucht A, Rosenholm JM
Förläggare: Multidisciplinary Digital Publishing Institute
Publiceringsår: 2019
Tidskrift: Pharmaceutics
Volym: 11
Nummer: 4
eISSN: 1999-4923


Abstrakt

Diseases in the respiratory tract rank among the leading causes of death
in the world, and thus novel and optimized treatments are needed. The
lungs offer a large surface for drug absorption, and the inhalation of
aerosolized drugs are a well-established therapeutic modality for local
treatment of lung conditions. Nanoparticle-based drug delivery platforms
are gaining importance for use through the pulmonary route. By using
porous carrier matrices, higher doses of especially poorly soluble drugs
can be administered locally, reducing their side effects and improving
their biodistribution. In this study, the feasibility of mesoporous
silica particles (MSPs) as carriers for anti-inflammatory drugs in the
treatment of airway inflammation was investigated. Two different sizes
of particles on the micron and nanoscale (1 µm and 200 nm) were
produced, and were loaded with dexamethasone (DEX) to a loading degree
of 1:1 DEX:MSP. These particles were further surface-functionalized with
a polyethylene glycol–polyethylene imine (PEG–PEI) copolymer for
optimal aqueous dispersibility. The drug-loaded particles were
administered as an aerosol, through inhalation to two different mice
models of neutrophil-induced (by melphalan or lipopolysaccharide) airway
inflammation. The mice received treatment with either DEX-loaded MSPs
or, as controls, empty MSPs or DEX only; and were evaluated for
treatment effects 24 h after exposure. The results show that the
MEL-induced airway inflammation could be treated by the DEX-loaded MSPs
to the same extent as free DEX. Interestingly, in the case of
LPS-induced inflammation, even the empty MSPs significantly
down-modulated the inflammatory response. This study highlights the
potential of MSPs as drug carriers for the treatment of diseases in the
airways.


Nyckelord

drug delivery, drug-delivery systems, Drug delivery systems, mesoporous materials, mesoporous silica, Mesoporous silica, Poorly soluble drug, Poorly soluble drugs, Poorly water-soluble drugs


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Senast uppdaterad 2020-10-04 vid 05:04