Browsing by Subject "Oral drug delivery"

Now showing 1 - 4 of 4

Open Access
Antibacterial nanofibers of pullulan/tetracycline-cyclodextrin inclusion complexes for fast-disintegrating oral drug delivery
(Elsevier Inc., 2021-12-08) Hsiung, E.; Celebioglu, A.; Chowdhury, R.; Kilic, M. E.; Durgun, Engin; Altier, C.; Uyar, T.
Tetracycline is a widely used antibiotic suffering from poor water solubility and low bioavailability. Here, hydroxypropyl-beta-cyclodextrin (HPβCD) was used to form inclusion complexes (IC) of tetracycline with 2:1 M ratio (CD:drug). Then, tetracycline-HPβCD-IC was mixed with pullulan- a non-toxic, water-soluble biopolymer - to form nanofibrous webs via electrospinning. The electrospinning of pullulan/tetracycline-HPβCD-IC was yielded into defect-free nanofibers collected in the form of a self-standing and flexible material with the loading capacity of ∼ 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-HPβCD nanofibers due to inclusion complexation. Through inclusion complexation with HPβCD, enhanced aqueous solubility and faster release profile were provided for pullulan/tetracycline-HPβCD-IC nanofibers compared to pullulan/tetracycline one. Additionally, pullulan/tetracycline-HPβCD-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-HPβCD-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.
Open Access
Fast-dissolving antibacterial nanofibers of cyclodextrin/antibiotic inclusion complexes for oral drug delivery
(Elsevier, 2020) Topuz, F.; Kılıç, M. E.; Durgun, Engin
Hypothesis The widespread use of antibacterial electrospun nanofibers is mostly restricted due to their low loading capacity to carry antibiotics and the need to use toxic organic solvents to boost the antibiotic loading capacity. Nanofibers based on natural excipients, such as cyclodextrin (CD)-based nanofibers, can carry larger amounts of antibiotics while achieving better stability via inclusion complexation. Experiments Nanofibers were produced by electrospinning and analyzed by electron microscopy to investigate the morphology of fibers. The formation of inclusion-complexation was analyzed by 1H NMR, FTIR, and XRD. Thermal analysis of the fibers was done using TGA. Ab initio modeling studies were done to calculate the complexation energies of antibiotics with CD. A disk-diffusion assay was used to test the antibacterial activity of the fibers. Findings Bead-free antibacterial nanofibers with mean diameters between 340 and 550 nm were produced. The formation of inclusion complexes (IC) between the CD and the antibiotics was confirmed by FTIR and 1H NMR, which was further verified by the disappearance of the crystalline peaks of antibiotics as determined by XRD analysis. Thermal analysis of the nanofibers revealed that the formulations showed good antibiotic encapsulation (45–90%). Ab initio simulations revealed that gentamicin had the highest complexation energy, followed by kanamycin, chloramphenicol, and ampicillin. The antibacterial nanofibers rapidly dissolved in water and artificial saliva, successfully releasing the CD antibiotic complexes. The nanofibers showed high antibacterial activity against Gram-negative Escherichia coli.
Open Access
Ondansetron/Cyclodextrin inclusion complex nanofibrous webs for potential orally fast-disintegrating antiemetic drug delivery
(Elsevier, 2022-07-25) Hsiung, E.; Celebioglu, A.; Emin Kilic, M.; Durgun, Engin
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 (HPβCD) 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/HPβCD 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 HPβCD resulted into faster and better release profile and quite faster disintegration property (∼2 s) in artificial saliva than polymeric ODS/PVA NW. Here, ODS/HPβCD 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/HPβCD NW might be a promising alternative to the polymeric based systems for the purpose of fast-disintegrating oral drug delivery.
Open Access
Orally fast disintegrating cyclodextrin/prednisolone inclusion-complex nanofibrous webs for potential steroid medications
(American Chemical Society, 2021-12-06) Çelebioğlu, A.; Wang, N.; Kılıç, M. E.; Durgun, Engin; Uyar, T.
Prednisolone is a widely used immunosuppressive and anti-inflammatory drug type that suffers from low aqueous solubility and bioavailability. Due to the inclusion complexation with cyclodextrins (CDs), prednisolone’s drawbacks that hinder its potential during the administration can be eliminated effectively. Here, we have early shown the electrospinning of free-standing nanofibrous webs of CD/prednisolone inclusion complexes (ICs) in the absence of a polymer matrix. In this study, hydroxypropyl-beta-CD (HPβCD) has been used to form ICs with prednisolone and generate nanofibrous webs with a drug loading capacity of ∼10% (w/w). Pullulan/prednisolone nanofibrous webs have been also fabricated as a control sample having the same drug loading (∼10%, w/w). It has been demonstrated that prednisolone has been found in an amorphous state in the HPβCD/prednisolone nanofibrous web due to inclusion complexation, while it has retained its crystal structure in the pullulan/prednisolone nanofibrous web. Therefore, the HPβCD/prednisolone IC nanofibrous web has shown a faster and enhanced release profile and superior disintegration feature in artificial saliva than the pullulan/prednisolone nanofibrous web. The complexation energy calculated using ab initio modeling displayed a more favorable interaction between HPβCD and prednisolone in the case of a molar ratio of 2:1 than 1:1 (CD: drug). Here, the HPβCD/prednisolone IC nanofibrous web has been developed without using a toxic component or solvent to dissolve drug molecules and boost drug loading in amorphous nature. The investigation of IC nanofibrous webs has been conducted to formulate a promising alternative to the orally disintegrating tablet formulation of prednisolone in the market. The nanofibrous structure and the improved physicochemical properties of prednisolone arising with the complexation might ensure a faster disintegration and onset of action against commercially available and orally disintegrating delivery systems during the desired treatment.