Fast-Disintegrating Nanofibrous Web of Pullulan/Griseofulvin-Cyclodextrin Inclusion Complexes.

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 (HPßCD) 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-HPßCD were prepared using a 1:2 molar ratio (GSF:HPßCD) 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-HPßCD-IC NF was obtained with a defect-free fiber morphology having 805 ± 180 nm average diameter. The self-standing and flexible PULL/GSF-HPßCD-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-HPßCD-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 HPßCD 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-HPßCD-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.

Ondansetron/Cyclodextrin inclusion complex nanofibrous webs for potential orally fast-disintegrating antiemetic drug delivery.

Ondansetron (ODS) is an effective antiemetic drug which suffers from limited solubility and bioavailability during oral administration due to first-pass metabolism. However, these limitations can be mitigated through inclusion complexation with cyclodextrins (CDs). In this study, we have reported the electrospinning of polymer-free, free-standing ODS/CD nanofibrous webs (NW), a promising approach for developing a fast-disintegrating delivery system of an antiemetic drug molecule. Highly water soluble hydroxypropyl-beta-cyclodextrins (HPßCD) were used as both complexation agent and electrospinning matrix. The computational study revealed that the 1/2 (drug/CD) stoichiometry was more favorable compared to 1/1. The ODS/HPßCD NW was obtained with higher loading efficiency (∼96 %) compared to the control sample of ODS/polyvinyl alcohol (PVA) NW (∼80 %). The amorphous distribution of ODS raised by complexation and the highly water-soluble nature of HPßCD resulted into faster and better release profile and quite faster disintegration property (∼2 s) in artificial saliva than polymeric ODS/PVA NW. Here, ODS/HPßCD NW was generated in the absence of a toxic solvent or chemical to enable the drug loading in an amorphous state. From all reasons above, ODS/HPßCD NW might be a promising alternative to the polymeric based systems for the purpose of fast-disintegrating oral drug delivery.

Antibacterial nanofibers of pullulan/tetracycline-cyclodextrin inclusion complexes for Fast-Disintegrating oral drug delivery.

Tetracycline is a widely used antibiotic suffering from poor water solubility and low bioavailability. Here, hydroxypropyl-beta-cyclodextrin (HPßCD) was used to form inclusion complexes (IC) of tetracycline with 2:1 M ratio (CD:drug). Then, tetracycline-HPßCD-IC was mixed with pullulan- a non-toxic, water-soluble biopolymer - to form nanofibrous webs via electrospinning. The electrospinning of pullulan/tetracycline-HPßCD-IC was yielded into defect-free nanofibers collected in the form of a self-standing and flexible material with the loading capacity of âˆ¼ 7.7 % (w/w). Pullulan/tetracycline nanofibers was also generated as control sample having the same drug loading. Tetracycline was found in the amorphous state in case of pullulan/tetracycline-HPßCD nanofibers due to inclusion complexation. Through inclusion complexation with HPßCD, enhanced aqueous solubility and faster release profile were provided for pullulan/tetracycline-HPßCD-IC nanofibers compared to pullulan/tetracycline one. Additionally, pullulan/tetracycline-HPßCD-IC nanofibers readily disintegrated when wetted with artificial saliva while pullulan/tetracycline nanofibers were not completely absorbed by the same simulate environment. Electrospun nanofibers showed promising antibacterial activity against both gram-positive and gram-negative bacteria. Briefly, our findings indicated that pullulan/tetracycline-HPßCD-IC nanofibers could be an attractive material as orally fast disintegrating drug delivery system for the desired antibiotic treatment thanks to its promising physicochemical and antibacterial properties.