Fast-Disintegrating Nanofibrous Web of Pullulan/Griseofulvin–Cyclodextrin Inclusion Complexes
Emmy Hsiung, Aslı Çelebioğlu, Mehmet Emin Kılıç, Engin Durgun, Tamer Uyar
Abstract
Griseofulvin (GSF) is one of the most widely used antifungal suffering from low water solubility and limited bioavailability. Here, cyclodextrin (CD) derivatives of hydroxypropyl-beta-CD (HPβCD) known for its high-water solubility were used to form inclusion complexes (ICs) with GSF. Here, the molecular modeling study revealed the more efficient complex formation with 1:2 (guest:CD) stoichiometry, so ICs of GSF-HPβCD were prepared using a 1:2 molar ratio (GSF:HPβCD) and then mixed with pullulan (PULL) to generate nanofibers (NFs) using the electrospinning technique. PULL is a nontoxic water-soluble biopolymer and the ultimate PULL/GSF-HPβCD-IC NF was obtained with a defect-free fiber morphology having 805 ± 180 nm average diameter. The self-standing and flexible PULL/GSF-HPβCD-IC NF was achieved to be produced with a loading efficiency of ∼98% corresponding to ∼6.4% (w/w) of drug content. In comparison, the control sample of PULL/GSF NF was formed with a lower loading efficiency value of ∼72% which equals to ∼4.7% (w/w) of GSF content. Additionally, PULL/GSF-HPβCD-IC NF provided an enhanced aqueous solubility for GSF compared to PULL/GSF NF so a faster release profile with ∼2.5 times higher released amount was obtained due to inclusion complexation between GSF and HPβCD within the nanofibrous web. On the other hand, both nanofibrous webs rapidly disintegrated (∼2 s) in the artificial saliva medium that mimics the oral cavity environment. Briefly, PULL/GSF-HPβCD-IC NF can be a promising dosage formulation as a fast-disintegrating delivery system for antifungal oral administration owing to the improved physicochemical properties of GSF.