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ELECTROSPINNING of BIOCOMPATIBLE POLYMERIC NANOFIBERS FUNCTIONALIZED with CYCLODEXTRIN INCLUSION COMPLEX A THESIS SUBMITTED TO THE MATERIALS SCIENCE AND NANOTECHNOLOGY PROGRAM OF GRADUATE SCHOOL OF ENGINEERING AND SCIENCE OF BILKENT UNIVERSITY IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE By Zeynep Aytaç August, 2012
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  • ELECTROSPINNING of BIOCOMPATIBLE POLYMERIC

    NANOFIBERS FUNCTIONALIZED with CYCLODEXTRIN

    INCLUSION COMPLEX

    A THESIS

    SUBMITTED TO THE MATERIALS SCIENCE AND NANOTECHNOLOGY

    PROGRAM OF GRADUATE SCHOOL OF ENGINEERING AND SCIENCE

    OF BILKENT UNIVERSITY

    IN PARTIAL FULFILLMENT OF THE REQUIREMENTS

    FOR THE DEGREE OF

    MASTER OF SCIENCE

    By

    Zeynep Ayta

    August, 2012

  • ii

    I certify that I have read this thesis and that in my opinion it is fully adequate, in scope

    and in quality, as a thesis of the degree of Master of Science.

    Assist. Prof. Dr. Tamer Uyar (Advisor)

    I certify that I have read this thesis and that in my opinion it is fully adequate, in scope

    and in quality, as a thesis of the degree of Master of Science.

    .

    Assist. Prof. Dr. Turgay Tekinay

    I certify that I have read this thesis and that in my opinion it is fully adequate, in scope

    and in quality, as a thesis of the degree of Master of Science.

    .

    Assist. Prof. Dr. Fatih Bykserin

    Approved for the Graduate School of Engineering and Science:

    .

    Prof. Dr. Levent Onural

    Director of the Graduate School of Engineering and Science

  • iii

    ABSTRACT

    ELECTROSPINNING of BIOCOMPATIBLE POLYMERIC

    NANOFIBERS FUNCTIONALIZED with CYCLODEXTRIN

    INCLUSION COMPLEX

    Zeynep Ayta

    M.S. in Materials Science and Nanotechnology

    Supervisor: Assist. Prof. Dr. Tamer Uyar

    August, 2012

    Electrospinning is a simple, versatile and cost-effective method to

    produce nanofibers. Electrospun nanofibers have high surface area to volume

    ratio and nanoporous structure. Moreover, electrospun nanofibers could be

    functionalized with additives to extend their application areas. Cyclodextrins

    (CDs) are cyclic oligosaccharides and have truncated-cone shape structure. Due

    to their hydrophobic cavity, CDs have ability to form inclusion complex (IC)

    with a variety of molecule. In our study, we functionalized electrospun

    nanofibers with CDs and CD-ICs.

    In the first part, we successfully produced hydroxypropyl cellulose-

    (HPC), carboxymethyl cellulose- (CMC) and alginate-based nanofibers via

    electrospinning. Then we functionalized these nanofibers with CDs. The

    morphological characterizations of nanofibers were performed through scanning

    electron microscopy (SEM). Here, we have combined the properties of both

    electrospun nanofibers and CDs, and these nanofibers could be used in drug

    delivery, wound healing and tissue engineering applications.

  • iv

    In the second part, we prepared IC of sulfisoxazole (SFS) (hydrophobic

    drug) with hydroxypropyl-beta-cyclodextrin (HPCD) (SFS/HPCD-IC). Then

    electrospinning of SFS/HPCD-IC incorporating hydroxypropyl cellulose

    (HPC) nanofibers were performed (SFS/HPCD-IC-HPC-NFs). In the third part

    of our study, we produced IC of -tocopherol (-TC) (antioxidant molecule)

    with beta-cyclodextrin (-CD) (-TC/-CD-IC); and polycaprolactone (PCL)

    nanofibers incorporating -TC/-CD-IC was obtained via electrospinning (-

    TC/-CD-PCL-NFs). In the fourth part, IC of allyl isothiocyanate (AITC)

    (antibacterial compound) with -CD (AITC/-CD-IC) was produced. The

    electrospinning of AITC/-CD-IC incorporating polyvinyl alcohol (PVA)

    nanofibers was carried out (AITC/-CD-IC-PVA-NFs). In the fifth part, IC of

    quercetin (QU) (antioxidant molecule) with -CD (QU/-CD-IC) was prepared;

    and polyacrylic acid (PAA) nanofibers incorporating QU/-CD-IC was obtained

    via electrospinning (QU/-CD-IC-PAA-NFs). The structural and thermal

    characterizations of SFS/HPCD-IC-HPC-NFs, -TC/-CD-PCL-NFs, AITC/-

    CD-IC-PVA-NFs and QU/-CD-IC-PAA-NFs were carried out by scanning

    electron microscopy (SEM), X-ray diffraction (XRD), differential scanning

    calorimetry (DSC) and thermogravimetric analysis (TGA). The amount of

    released molecules were determined via liquid chromatography-mass

    spectroscopy (LC-MS) for SFS/HPCD-IC-HPC-NFs; high performance liquid

    chromatography (HPLC) for -TC/-CD-PCL-NFs and QU/-CD-IC-PAA-NFs

    and gas chromatography-mass spectrometry (GC-MS) for AITC/-CD-IC-PVA-

    NFs. The antioxidant activity of -TC/-CD-PCL-NFs and QU/-CD-IC-PAA-

    NFs was investigated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical

    scavenging assay. Moreover, -TC/-CD-PCL-NFs released great proportion of

    -TC after exposing UV light. Thus, -TC/-CD-PCL-NFs exhibited quite high

    photostability. The antibacterial activity of AITC/-CD-IC-PVA-NFs was

    evaluated by colony counting method against Escherichia coli (E.coli) and

    Staphylococcus aureus (S.aureus). In brief, we concluded that SFS/HPCD-IC-

    HPC-NFs, -TC/-CD-PCL-NFs, AITC/-CD-IC-PVA-NFs and QU/-CD-IC-

    PAA-NFs are promising materials for drug delivery and wound healing

    applications.

  • v

    Keywords: electrospinning, nanofibers, biopolymers, cyclodextrin, inclusion

    complex, sulfisoxazole, -tocopherol, allyl isothiocyanate, quercetin, controlled

    release.

  • vi

    ZET

    ELEKTROERME YNTEM LE SKLODEKSTRN

    NKLZYON KOMPLEKSLERYLE

    FONKSYONLATIRILMI BYOUYUMLU NANOLFLERN

    RETLMES

    Zeynep Ayta

    Yksek Lisans, Malzeme Bilimi ve Nanoteknoloji Blm

    Tez Yneticisi: Yard. Do. Dr. Tamer Uyar

    Austos, 2012

    Elektroeirme nanolif elde etmek iin basit, verimli ve maliyeti dk bir

    yntemdir. Elektroeirme yntemiyle elde edilen nanolifler yksek yzey

    alanna ve nano boyutta gzenekli yapya sahiptir. Dahas, bu nanolifler

    uygulama alanlarn geniletmek amacyla katk maddeleri ile fonksiyonel hale

    getirilebilirler. Siklodekstrinler (CD), kesik koni eklindeki siklik

    oligosakkaritlerdir. Hidrofobik kaviteleri sayesinde, pek ok moleklle

    inklzyon kompleksi (IC) oluturabilirler. almalarmzda, elektroeirme

    yntemiyle elde edilen nanolifleri CD ve CD-IC ile fonksiyonel hale getirdik.

    lk ksmda, hidroksipropil selloz (HPC), karboksimetil selloz (CMC)

    ve aljinat nanoliflerini elektroeirme yntemi ile baaryla rettik. Daha sonra

    bu nanolifleri CDlerle fonksiyonel hale getirdik. Bu nanoliflern morfolojik

    karakterizasyonlar taramal electron mikroskobu (SEM) yardmyla yapld.

    Burada, elektroeirme ile retilen nanoliflerin ve CDlerin zelliklerini

  • vii

    birletirmi olduk. Bu nanolifler ila salm, yara iyiletirme ve doku

    mhendislii alanlarnda kullanlabilirler.

    kinci ksmda, slfisoksazol (SFS) (hidrofik ila) ile hidroksipropil-beta-

    siklodekstrin (HPCD) inklzyon kompleksini (IC) (SFS/HPCD-IC)

    hazrladk. Daha sonra SFS/HPCD-IC ieren hidroksipropil selloz (HPC)

    nanolifleri elektroeirme yntemiyle retildi. almamzn nc ksmnda, -

    tokoferol (-TC) (antioksidan madde) ile beta-siklodekstrin (-CD) IC (-TC/-

    CD-IC) rettik; ve -TC/-CD-IC ieren polikprolakton (PCL) nanolifleri

    elektroeirme ile elde edildi (-TC/-CD-IC-PCL-NFs). Drdnc ksmda, alil

    izotiyosiyanat (AITC) (antibakteriyel madde) ile -CD IC (AITC/-CD-IC)

    retildi. AITC/-CD-IC ieren polivinil alkol (PVA) nanolifleri elektroeirme

    ile retildi (AITC/-CD-IC-PVA-NFs). Beinci ksmda, kuersetin (QU)

    (antioksidan madde) ile -CD IC (QU/-CD-IC) hazrland ve QU/-CD-IC

    ieren poliakrilik asit (PAA) nanolifleri elektroeirme ile elde edildi (QU/-

    CD-IC-PAA-NFs). SFS/HPCD-IC-HPC-NFs, -TC/-CD-IC-PCL-NFs,

    AITC/-CD-IC-PVA-NFs ve QU/-CD-IC-PAA-NFsnin yapsal ve sl

    karakterizasyonlar taramal elektron mikroskobu (SEM), X-n krnm

    (XRD), diferansiyel tarama kalorimetrisi (DSC) ve termogravimetrik analiz

    (TGA) ile yapld. Nanoliflerden salnan molekllerin miktar SFS/HPCD-IC-

    HPC-NFs iin sv kromatografisi-ktle spektrometresi (LC-MS); -TC/-CD-

    IC-PCL-NFs ve QU/-CD-IC-PAA-NFs iin yksek performansl sv

    kromatografisi (HPLC) ve AITC/-CD-IC-PVA-NFs iin gaz kromatografisi-

    ktle spektrometresi (GC-MS) yardmyla belirlendi. -TC/-CD-IC-PCL-NFs

    ve QU/-CD-IC-PAA-NFsnin antioksidan aktivitesi 2 2-difenil-1-pikrilhidrazil

    (DPPH) radikal temizleme testiyle incelendi. Dahas, -TC/-CD-PCL-NFs UV

    na maruz brakldktan sonra da -TCnin byk bir ksmn salmtr. Bu

    nedenle, -TC/-CD-IC-PCL-NFs olduka yksek fotostabilite gstermitir.

    AITC/-CD-IC-PVA-NFsnin Escherichia coli (E.coli) and Staphylococcus

    aureusa kar antibakteriyel etkisi koloni sayma metoduyla belirlendi. Ksacas,

    SFS/HPCD-IC-HPC-NFs, -TC/-CD-IC-PCL-NFs, AITC/-CD-IC-PVA-

    http://tureng.com/search/termogravimetrik%20analizi

  • viii

    NFs ve QU/-CD-IC-PAA-NFsnin ila salm ve yara iyiletirme

    uygulamalarnda gelecek vadeden malzemeler olduklar sonucunda vardk.

    Anahtar Kelimeler: elektroeirme, nanolif, biyopolimer, siklodekstrin,

    inklzyon kompleks, slfisoksazol, -tokoferol, alil izotiyosiyanat, kuersetin,

    kontroll salm.

  • ix

    ACKNOWLEDGEMENT

    I would like to express my sincerest gratitude to my supervisor Assist. Prof. Dr.

    Tamer Uyar for his guidance, support, patience and providing me with an

    excellent atmosphere for doing research.

    I would like to thank the members of my group members Asl elebiolu,

    Fatma Kayac and Yelda Erta for their support and valuable friendship.

    I would like to thank Asst. Prof. Dr. Turgay Tekinay and his student zgn

    Candan Onarman Umu for their collaboration in antibacterial test experiments.

    I would like to acknowledge State Planning Organization (DPT) of Turkey for

    its su