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Photonic crystals in biology

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P<br />

P<br />

P Hacettepe<br />

P Hacettepe<br />

P<br />

P<br />

Poster Session, Tuesday, June 15<br />

Theme A1 - B702<br />

Preparation and Characterization of Bacterial Polyester Based Nanoparticlesfor Targeted Delivery of<br />

Etoposide<br />

1<br />

2<br />

3<br />

1<br />

2,3<br />

UEbru KlçayUP P, Eylem GüvenP P, Mustafa TürkP P, Baki HazerP P, Emir Baki DenkbaP<br />

P*<br />

1<br />

2<br />

3<br />

PKaraelmas University, Chemistry Department, Physical Chemistry Division, , Zonguldak, Turkey<br />

University, Nanotechnology and Nanomedic<strong>in</strong>e Division, 06532, Beytepe, Ankara, Turkey<br />

University, Chemistry Department, Biochemistry Division, 06532 Beytepe, Ankara, Turkey<br />

4<br />

PKırıkkale University, Biology Department, Biochemistry Division, Kırıkkale, Turkey<br />

Abstract-Tumour-specific nano-structured drug delivery systems have received much attention due to their unique accumulation at tumour<br />

region. Among them polymeric nanoparticles made from natural polymers have drawn major attention due to higher stability, maneuverability<br />

for <strong>in</strong>dustrial manufacture, and opportunity for further surface nanoeng<strong>in</strong>eer<strong>in</strong>g. Aim of this study was to to prepare and characterize etoposideloaded,<br />

folic acid conjugated poly(3- hydroxybutyrate-co-3 hydroxyhexanoate) (PHBHHx) nanoparticles for us<strong>in</strong>g <strong>in</strong> targeted cancer therapy.<br />

Result<strong>in</strong>g data showed that etoposide-loaded and folic acid modified PHBHHX nanoparticles show promise for targeted delivery of etoposide to<br />

cancer cells.<br />

Nanotechnology is an emerg<strong>in</strong>g multidiscipl<strong>in</strong>ary field for<br />

current research and development <strong>in</strong> all technical discipl<strong>in</strong>es.<br />

Nanoparticulate drug delivery systems which are nanometric<br />

carriers used to deliver drugs or biomolecules have received<br />

great attention over the last decades. Polymeric nanoparticles<br />

have been widely <strong>in</strong>vestigated for both diagnosis and targeted<br />

treatment of cancer; because they (a) can show controlled<br />

release properties, (b) can pass through the smallest capillary<br />

vessels and avoid rapid clearance by phagocytes, (c) can<br />

penetrate cells and tissue gap <strong>in</strong> order to arrive at target<br />

organs, (d) can reduce side effects of drugs, (e) can <strong>in</strong>crease<br />

drug efficacy, etc [1,2].<br />

Polyhydroxyalkanoates (PHAs) are a promis<strong>in</strong>g class of new<br />

emerg<strong>in</strong>g biopolymers. They are the polyesthers of<br />

hydroxyalkanoate produced by a variety of bacterial species as<br />

an <strong>in</strong>tracellular carbon and energy compound under nutrientlimit<strong>in</strong>g<br />

conditions with excess carbon. There has been<br />

considerable <strong>in</strong>terest <strong>in</strong> us<strong>in</strong>g them as drug carriers due to their<br />

biodegradability and biocompatibility. A newer member of<br />

PHA family, poly(3-hydroxybutyrate-co-3 hydroxyhexanoate)<br />

(PHBHHx), is currently be<strong>in</strong>g produced <strong>in</strong> large scale [3,4].<br />

Studies have demonstrated that PHBHHx, a microbially<br />

synthesized polyester with good biodegradability and<br />

biocompatibility, as well as strong mechanical properties,<br />

consequently, is very promis<strong>in</strong>g for biomedical applications.<br />

In the presented study poly(3-hydroxybutyrate-co-3-<br />

hydroxyhexanoate) nanoparticles were prepared to use <strong>in</strong><br />

targeted cancer therapy. PHBHHX nanoparticles were<br />

prepared by solvent evaporation technique us<strong>in</strong>g<br />

dichloromethane as the solvent and tween-80 as the emulsifier.<br />

Morphological evaluations of the prepared nanoparticles were<br />

<strong>in</strong>vestigated by us<strong>in</strong>g atomic force microscopy (AFM). Effect<br />

of stirr<strong>in</strong>g rate, amount of surfactant and polymer<br />

concentration on nanoparticle size were <strong>in</strong>vestigated by Zeta<br />

Size Analyser. The size of the smallest nanoparticles obta<strong>in</strong>ed<br />

was <strong>in</strong> the range of 190-220 nm. Etoposide, an ant<strong>in</strong>eoplastic<br />

agent was loaded <strong>in</strong>to nanoparticles and drug release profiles<br />

were obta<strong>in</strong>ed. 16-30 % drug load<strong>in</strong>g was observed <strong>in</strong> drug<br />

load<strong>in</strong>g studies depend<strong>in</strong>g on the <strong>in</strong>itial drug content. Release<br />

studies of etoposide were also evaluated. For ‘active’ target<strong>in</strong>g<br />

of cancerous cells; nanoparticles were modified with folic acid<br />

as the model ligand for target<strong>in</strong>g nanoparticles to cancer cells.<br />

The receptor for folic acid is upregulated <strong>in</strong> many human<br />

cancers, <strong>in</strong>clud<strong>in</strong>g malignancies of the ovary, kidney, bra<strong>in</strong>,<br />

breast myeloid cells and lung. Therefore it can be utilized as a<br />

useful target for tumor-specific drug delivery [5]. Different<br />

concentrations of folic acid was used <strong>in</strong> order to <strong>in</strong>vestigate<br />

the effect of ligand concentration on ligand b<strong>in</strong>d<strong>in</strong>g efficiency.<br />

Ligand b<strong>in</strong>d<strong>in</strong>g efficiency was found to be between 71-93%.<br />

Additionally physicochemical structures of nanoparticles were<br />

analyzed by us<strong>in</strong>g FTIR and the system was optimized for<br />

further <strong>in</strong> vitro and <strong>in</strong> vivo applications.<br />

Obta<strong>in</strong>ed results showed that etoposide-loaded and folic acid<br />

modified PHBHHX nanoparticles show promise for targeted<br />

cancer therapy.<br />

*Correspond<strong>in</strong>g author: denkbas@hacettepe.edu.tr<br />

[1] Paul, D.R., Robeson, L.M. ‘’Polymer nanotechnology:<br />

Nanocomposites’’, Polymer 49 (2008) 3187-3204.<br />

[2] Ferrari, M. Cancer nanotechnology: Opportunities and challenges.<br />

Nat Rev Cancer (2005) 161–71.<br />

[3] Bayram, C., Denkbas, E.B., Kiliçay, E., Hazer, B., Çakmak, H.B.<br />

‘Preparation and Characterization of Triamc<strong>in</strong>olone Acetonideloaded<br />

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHx)<br />

Microspheres’ Journal of Bioactive and Compatible Polymers 2008;<br />

23; 334.<br />

[4] Z<strong>in</strong>n, M., Witholt, B., Egli, T. ‘’Occurrence, synthesis and<br />

medical application of bacterial polyhydroxyalkanoate’’Advanced<br />

Drug Delivery Reviews, 53 (2001) 5-21.<br />

[5] Lu, Y., Low, P.S. ‘’Folate-mediated delivery of macromolecular<br />

anticancer therapeutic agents’’ Advanced Drug Delivery Review,. 54<br />

(2002) 675-693.<br />

6th Nanoscience and Nanotechnology Conference, zmir, 2010 264

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