Development of PEG and PEG-peptide based drug delivery systems
tarafından
 
Balcı, Beste, author.

Başlık
Development of PEG and PEG-peptide based drug delivery systems

Yazar
Balcı, Beste, author.

Yazar Ek Girişi
Balcı, Beste, author.

Fiziksel Tanımlama
x, 71 leaves: color illustraltions.+ 1 computer laser optical disc.

Özet
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.

Konu Başlığı
Peptide drugs.
 
Hydrazine.
 
Polyethylene glycol.

Yazar Ek Girişi
Top, Ayben

Tüzel Kişi Ek Girişi
İzmir Institute of Technology. Chemical Engineering.

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.


LibraryMateryal TürüDemirbaş NumarasıYer NumarasıDurumu/İade Tarihi
IYTE LibraryTezT001524TP248.65.P58 B174 2016Tez Koleksiyonu