title: Electrospun polycaprolactone nanofibers as a potential oromucosal delivery system for poorly water-soluble drugs.
abstract: The number of poorly water-soluble drug candidates is rapidly increasing; this represents a major challenge for the pharmaceutical industry. As a consequence, novel formulation approaches are required. Furthermore, if such a drug candidate is intended for the therapy of a specific group of the population, such as geriatric or pediatric, the formulation challenge is even greater, with the need to produce a dosage form that is acceptable for specific patients. Therefore, the goal of our study was to explore electrospun polycaprolactone (PCL) nanofibers as a novel nanodelivery system adopted for the oromucosal administration of poorly water-soluble drugs. The nanofibers were evaluated in comparison with polymer films loaded with ibuprofen or carvedilol as the model drugs. Scanning electron microscopy revealed that the amount of incorporated drug affects the diameter and the morphology of the nanofibers. The average fiber diameter increased with a higher drug loading, whereas the morphology of the nanofibers was noticeably changed in the case of nanofibers with 50% and 60% ibuprofen. The incorporation of drugs into the electrospun PCL nanofibers was observed to reduce their crystallinity. Based on the morphology of the nanofibers and the films, and the differential scanning calorimetry results obtained in this study, it can be assumed that the drugs incorporated into the nanofibers were partially molecularly dispersed in the PCL matrix and partially in the form of dispersed nanocrystals. The incorporation of both model drugs into the PCL nanofibers significantly improved their dissolution rates. The PCL nanofibers released almost 100% of the incorporated ibuprofen in 4h, whereas only up to 77% of the incorporated carvedilol was released during the same time period, indicating the influence of the drug's properties, such as molecular weight and solubility, on its release from the PCL matrix. The obtained results clearly demonstrated the advantages of the new nanodelivery system compared to the drug-loaded polymer films that were used as the reference formulation. As a result, electrospinning was shown to be a very promising nanotechnology-based approach to the formulation of poorly water-soluble drugs in order to enhance their dissolution. In addition, the great potential of the produced drug-loaded PCL nanofiber mats for subsequent formulation as oromucosal drug delivery systems for children and the elderly was confirmed.
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Potrč
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Saša
authors.initials: S
authors.lastname: Baumgartner
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Robert
authors.initials: R
authors.lastname: Roškar
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Odon
authors.initials: O
authors.lastname: Planinšek
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Lavrič
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Julijana
authors.initials: J
authors.lastname: Kristl
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia. Electronic address: petra.kocbek@ffa.uni-lj.si.
authors.forename: Petra
authors.initials: P
authors.lastname: Kocbek
mesh_terms: D000284:Administration, Oral; D002152:Calorimetry, Differential Scanning; D002227:Carbazoles / Q000737:chemistry; D000077261:Carvedilol; D016503:Drug Delivery Systems; D007052:Ibuprofen / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009061:Mouth Mucosa; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D011091:Polyesters / Q000737:chemistry*; D011412:Propanolamines / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical; D014867:Water / Q000737:chemistry
chemical_list: D002227:Carbazoles; D011091:Polyesters; D011412:Propanolamines; D014867:Water; D000077261:Carvedilol; C016240:polycaprolactone; D007052:Ibuprofen
keywords: Electrospinning; Nanofibers; Oromucosal drug delivery; Polycaprolactone; Poorly soluble drugs