Cyclodextrinbased microspheres containing mucoadhesive polymers for nasal administration

Abstract

Nasal drug delivery has the last decades been explored as an alternative route for the administration of drugs with poor bioavailability and for the delivery of biosensitive and high molecular weight compounds such as proteins, peptides, steroids and vaccines, as well as for brain targeting of drugs. The use of polymers such as chitosan, alginate and pectin for this purpose is interesting because they are biocompatible, non-toxic and have mucoadhesive properties useful for the nasal administration of drugs (Hillary et al., 2001, Gavini et al., 2005). The aim of this study was the design, preparation and evaluation of mucoadhesive microspheres containing cyclodextrins (CDs) for nasal administration and hence targeting the cyclodextrin to the brain.

Twelve batches of microspheres containing the polymers sodium alginate, chitosan hydrochloride or pectin loaded with â-cyclodextrin or its derivate hydroxypropyl-â-cyclodextrin (HP-CD) in two different CD to polymer ratio were produced using a spray drying technique. The effect of combining chitosan and alginate were studied by mixing the microspheres with polymer powder. The microspheres were then characterised with respect to properties such as drug content, particle size, morphology and for their water uptake capacity. Also in vitro dissolution tests were carried out. The mucoadhesive abilities and the permeation of CD were ex vivo investigated using sheep nasal mucosa as a model. All tests were performed for the raw CDs as a comparison.

The microspheres prepared by the spray drying technique show high encapsulation efficiencies of CD, are characterised by small particle sizes, and present smooth, spherical morphologies. All the formulations have the ability to absorb water and delay the dissolution rate of the CDs in vitro. While by combining alginate and chitosan, more controlled in vitro release rates were obtained. The ex vivo experiments confirm good mucoadhesive properties of the microspheres and the permeation tests revealed that HP-CD is able to permeate through nasal sheep mucosa, the batches containing polymers HP-chit 1:1 and HP-chit 2:1 + algi are able to control the rate of CD permeation compared to raw HP-CD. The characteristics of the microspheres are influenced by the kind of polymer, cyclodextrin, and CD to polymer ratio used. All the formulations show characteristics suitable for nasal administration and hence are promising for a future delivery device for targeting cyclodextrin to the brain.