PEG-DA/Conconavalin A Biyokompozit Hidrojel Sentezi ve Kanser Tedavisi İçin Araştırılması

Öz

Kanser tedavisinde ilaç terapisi önemli bir araştırma alanını oluşturmaktadır. Conconavalin A(ConA) kanser hücreleri ile etkileşime girebildiği için anti-kanser ilaç çalışmalarında kullanılan bir lektindir. Bu çalışmada, ConA ve polietilen glikol diakrilat (PEGDA) kullanılarak hidrojel sentezi yapılmıştır. Sentezlenen hidrojellerin Fourier dönüşümlü infrared spektroskopisi ( FTIR) ve Taramalı Elektron mikroskobu (SEM) ile karakterizasyonu yapılmıştır. Hidrojellerin karakterizasyonunu incelediğimizde, PEGDA/ConA’nın birbirine entegre olduğu, biyokompozitlerin sentezlendiği gözlenmiştir. Sentezlenen hidrojellerin pH=7,4 ve 1,2’de dinamik şişme davranışları incelenmiştir. Sentezlenen PEGDA/ConA biyokompozit hidrojellerin şişme davranışlarını incelediğimizde yaklaşık 60 dakidada maksimuma ulaştığı gözlenmiştir. PEGDA/ConA hidrojellere geniş spektrumlu bir antibiyotik olan gentamisin yüklenmiş ve gentamisin yüklü hidrojellerin pH=7,4 ve pH=1,2’de ilaç salım davranışları incelenerek, karşılaştırılmıştır. PEGDA/ConA biyokompozit hidrojellerin pH=1,2 ilaç salım davranışlarına bakıldığında 400 dakikada ilaç salımının %15-20 civarında olduğu, pH=7,4’te ise 400 dakikada ilaç salımının %60’larda görülmüştür. Uzun süreli salım çalışmalarında kullanılabilecek ilaç salım sistemi olarak tasarımının uygun olduğu görülmüştür. Böylece anti-kanser ilaç salımında PEGDA/ConA hidrojellerin kullanılabileceği görülmüştür.

Anahtar Kelimeler

• PEGDA
• Conconavalin A
• Biyokompozit
• Hidrojel
• Kanser Tedavisi

PEG-DA/Concanavalin A Biocomposite Hydrogels Synthesis And Investigations For Cancer Therapy

Öz

Drug therapy is an important research area in cancer treatment. Conconavalin a (ConA) is a lectin used for anti-cancer drug research because it can interact with cancer cells. In this study, hydrogels was synthesized using ConA and polyethylene glycol diacrylate (PEGDA). Synthesized hydrogels were characterized by Fourier-Transform Infrared Spectroscopy (FTIR) and the Scanning Electron microscope (SEM). When we examined at the characterization of hydrogels, it was observed that PEGDA/ConA was integrated and that biocomposites were synthesized. Dynamic swelling behavior of synthesized hydrogels were studied at pH = 7.4 and 1.2. When we examined the swelling behavior of synthesized PEGDA/ConA hydrogels, it was observed that biocomposite hydrogels reached maximum in approximately 60 minutes. PEGDA/ConA hydrogels were loaded gentamisin, a broad spectrum antibiotic,and drug release behavior of gentamicin loaded hydrogels at pH=7.4 and pH=1.2 were investigated and compared. Considering the drug release behavior of PEGDA/ConA biocomposite hydrogels at pH=1,2, it was observed that the drug release was around 15-20% in 400 minutes, and that the drug release was around 60% in 400 minutes at pH=7,4. It has been found that its design is suitable as a drug delivery system that can be used in long-term release studies. Thus, it has been seen that PEGDA/ConA hydrogels can be used in anti-cancer drug release.

Anahtar Kelimeler

• PEGDA
• Conconavalin A
• Biocomposite
• Hydrogels
• Cancer Therapy

Kaynakça

1. Chung, B.G., Lee,K-H., Khademhosseini A., Lee S-H. (2012). Microfluidic fabrication of microengineered hydrogels and their application in tissue engineering. Lab Chip, 12, 45-59. DOI: 10.1039/C1LC20859D
2. Elshal M.F., Eid N.M., El-Sayed I., El-Sayed W., Al‐Karmalawy A.A. (2022) Concanavalin-A Shows Synergistic Cytotoxicity with Tamoxifen via Inducing Apoptosis in Estrogen Receptor-Positive Breast Cancer: In Vitro and Molecular Docking Studies. Pharmaceutical Sciences, 2022, 28(1), 76-85.doi:10.34172/PS.2021.22
3. Gholamali I. (2021) Stimuli-Responsive Polysaccharide Hydrogels for Biomedical Applications: a Review Regenerative Engineering and Translational Medicine, 7:91–114. https://doi.org/10.1007/s40883-019-00134-1
4. Gomez H.I.O., Martins C.S.M., Prior J. A. V (2021) Silver Nanoparticles as Carriers of Anticancer Drugs for Efficient Target Treatment of Cancer , Nanomaterials, 11,964. https://doi.org/10.3390/nano11040964
5. Hwang C.W, Kwak N.S, Hwang, T.S. (2013). Preparation of poly(GMA-co-PEGDA) microbeads modified with iminodiacetic acid and their indium adsorption properties, Chemical Engineering Journal, 226,79–86. https://doi.org/10.1016/j.cej.2013.04.041
6. Narayanaswamy, R. ve Torchilin V.P. (2019). Hydrogels and Their Applications in Targeted Drug Delivery. Molecules, 24(3),603; https://doi.org/10.3390/molecules24030603
7. Novak U. ve Grdadolnik J. (2017).The Hydration of Concanavalin A studied by infrared spectroscopy. Journal of Molecular Structure, 1135, 138-143. https://doi.org/10.1016/j.molstruc.2017.01.052
8. Peppas, N.A.,Bures, P., Leobandung, W., Ichikawa, H. (2000). Hydrogels in pharmaceutical formulation. Eur. J. Pharm. Biopharm.,50: 27-46. Doi: 10.1016/s0939-6411(00)00090-4.

9. Ramaknishna, S., Mayer, J., Wintermantel, E., Leong, K. W. (2001). Biomedical Applications of Polymer-Composite Materials: A Review. Composite Science and Technology, 61, 1189-1224. https://doi.org/10.1016/S0266-3538(00)00241-4
10. Sant, S., Tao S.L., Fisher O.Z., Xu Q., Peppas N.A., Khademhosseini A. (2012). Microfabrication Technologies for drug delivery. Advanced Drug Delivery Reviews, 64,496–507. DOI: 10.1016/j.addr.2011.11.013
11. Shoichet, M.S. (2010). Polymer Scaffolds for Biomaterials Applications. Macromolecules, 201, 43, 581-591. https://doi.org/10.1021/ma901530r
12. Yi, J.Z., Lin K., Wu H. Mao X., Zhang L.M., Yang L. (2021). Smart controlled release of acarbose from glucose-sensitive hydrogels comprising covalently modified carboxylated pullulan and concanavalin A. Journal of Applied Polymer Science, 138:e51553.https://doi.org/10.1002/app.51553
13. Zhang, X., Yang, D., Nie J. (2008). Chitosan/Polyethylene Glycol Diacrylate Films as Potential Wound Dressing Material. International Journal of Biological Macromolecules, 43, 456–462. doi:10.1016/j.ijbiomac.2008.08.010.