Development of PEG and PEG-peptide based drug delivery systems için kapak resmi
Development of PEG and PEG-peptide based drug delivery systems
Balcı, Beste, author.
Yazar Ek Girişi:
Fiziksel Tanımlama:
x, 71 leaves: color illustraltions.+ 1 computer laser optical disc.
In this study, two types of drug delivery systems (DDS) were prepared; mPEG (methoxy polyethylene glycol)-HYD (hydrazide)-DOX and mPEG-peptide-(HYD)-DOX. In the design of the conjugates, mPEG was used to increase the blood circulation time. HYD provided an acid cleavable bond between the carrier molecule and DOX, whereas peptide containing histidines imparted pH responsiveness of the molecule. Doxorubicin (DOX) was selected as a model anti-cancer drug. DDS were synthesized using two steps; hydrazide functionalization of carboxylic acid of the carrier molecule followed by DOX conjugation. Hydrazide form of the carrier molecules denoted as HYD1 and HYD2 were obtained using adipic acid dihydrazide (AADH) and carbohydrazide (CH), respectively. To increase DOX conjugation, trifluoroacetic acid (TFA) and DOX amounts were changed and the reactions were carried out at the conditions giving the highest DOX conjugation (mPEG-HYD:DOX:TFA= 2.5mg:2mg:20μL per 1 mL of DMSO). The peptide (AT1=CGGGHHHHHHGGGE) was synthesized using solid phase peptide synthesis (SPPS) and PEGylated using mPEG-maleimide to obtain mPEG-AT1 conjugate. The purity of AT1 and mPEG-AT1 were confirmed using mass spectroscopy and high performance liquid chromatography (HPLC). DOX conjugation percentages were obtained as 62  7, 60  3 and 35 + 3 for mPEG-HYD1-DOX, mPEG-HYD2-DOX and mPEG-AT1-HYD1-DOX, respectively. Drug release studies indicated modest pH responsiveness of the carrier molecules obtained using AADH. On the other hand, mPEG-HYD2-DOX released  13% of drug at the end of the 72h independent of pH. For mPEG-AT1-DOX, drug release percentage values were obtained as  15% and  30% at pH 7.4 and 5.0 respectively. Cytotoxicity of the conjugates of DDS was determined using lung cancer (A-549) cell lines. DOX equivalent IC50 values were determined as 20, 40 and 5 for mPEG-HYD1-DOX, mPEG-HYD2-DOX and mPEG-AT1-DOX respectively.
Yazar Ek Girişi:
Tek Biçim Eser Adı:
Thesis (Master)--İzmir Institute of Technology: Chemical Engineering.

İzmir Institute of Technology: Chemical Engineering--Thesis (Master).
Elektronik Erişim:
Access to Electronic Versiyon.


Materyal Türü
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Durumu/İade Tarihi
Tez T001524 TP248.65.P58 B174 2016

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