A comparative study of a range of polymeric microspheres as potential carriers for the inhalation of proteins

Abstract

1The aim of this study was to compare protein-loaded inhalable microparticles 2 manufactured using a range of biocompatible polymers including hydroxypropyl cellulose 3 (HPC), chitosan, hyaluronic acid, alginate, gelatin, ovalbumin and poly (lactide-co-4 glycolide)(PLGA). Spray drying was used to prepare microparticles containing bovine 5 serum albumin labeled with flourescein isothiocyanate (BSA-FITC). Particles of respirable 6 size and high protein loading were obtained. No evidence of BSA degradation was seen 7 from PAGE analysis. The microparticles were mixed with mannitol as a carrier and 8 powder aerosolization was assessed with a multi-dose dry powder inhaler (DPI) using a 9 multi-stage cascade impactor. The mass median aerodynamic diameter (MMAD) ranged 10 between 2.9-4.7m. Potential polymer toxicity in the lungs was compared by impinging 11 the particles on Calu-3 monolayers and assessing the cytotoxicity, induction of cytokine 12 release, changes in transepithelial permeability and electrical resistance. No toxic effects 13were observed with most of the polymers though some evidence of compromised cell 14 monolayer integrity was seen for PLGA and ovalbumin. PLGA and gelatin microparticles 15 caused a significant increase in IL-8 release. Of the polymers studied, PLGA showed the 16 greatest toxicity. Certain polymers showed particular promise for specific protein delivery 17 needs in the lungs, such as HPC to improve flow properties, sodium hyaluronate for 18 controlled release, and chitosan and ovalbumin for systemic delivery. 19

Influence of key parameters on the morphology of ethylcellulose microcapsules prepared via room-temperature spray drying

“…In the past considerable effort has been dedicated to the fabrication of polymeric microspheres via spray drying, owing primarily to the favorable drug-delivery characteristics of such systems (Ameye et al 2005;Brandhonneur et al 2009;Bruinsma et al 1997;da Silva et al 2009;De Rosa et al 2005;Gomez-Gaete et al 2008;Kim et al 2000Kim et al , 2005Mi et al 2003;Mok and Park 2008;Mundargi et al 2008;Naraharisetti et al 2005;Qian et al 2009;Sivadas et al 2008;Yin and Yates 2009;Zinn et al 2001). Generally, a microcapsule/microsphere is a system containing a well-defined core and a distinct shell, with the core usually being a liquid or a solid (Mathiowitz 1999).…”

‘Smart‘ non-viral Delivery Systems for Targeted Delivery of RNAi to the Lungs

“…Spray drying involves atomisation of a drug solution into a current of gas (air or nitrogen) which has been heated to a temperature sufficient to evaporate the solvent. The solvent in the sprayed droplets is thus removed and the dry drug/excipient particles are collected in a chamber (Figure 1) [21]. In sprayfreeze drying, a solution containing the drug of interest is sprayed into a vessel containing a cryogenic liquid such as nitrogen.…”

Studies on the preparation and in vitro - in vivo evaluation of mucoadhesive microspheres of glycyrrhetinic acid isolated from liquorice

“…However, the success of microspheres as a drug delivery system is limited due to their short sustaining time at the site of absorption. This limitation can be overcome by incorporating a mucoadhesive to the microspheres, which would be extending the sustaining time of microspheres at the site of absorption by providing an intimate adhesive contact of the drug delivery system with the absorbing membranes (Shukla and Tiwari, 2012;Sinha et al, 2004;Sivadas et al, 2008).…”