Clearance profile of radioactive gold nanoparticle (198Au) conjugates-poliamidoamin generation 4-nimotuzumab ; potential radio-pharmaceutical theranostic agent

Nurhatidjah Awaliyah Halid, Abdul Mutalib, Anung Pujiyanto, Adang Hardi Gunawan

Abstract


Theranostic agents are agents that combine diagnostic and therapeutic capabilities into a single agent. The presence of conjugated cancer which is therapeutic agents such as nimotuzumab monoclonal antibodies with radioactive gold nanoparticles stabilized with Polyamidoamine Generation 4 (PAMAM G4) dendrimer can actively interact with specific cancer cells. Radioactive gold (198Au) as a radiation transmitter β (961 keV) capable for killing cancer cells and (412 keV) γ rays that give a golden image in the body, thus acting as a theranostic agent. The purpose of this study was to obtain confident results of conjugate safety by observing the constituent clearance of 198AuNP-PAMAM G4-Nimotuzumab. The result of the conjugate clearance will be the reference for the metabolic state as a new, stable and complete radiofarmaka upon reaching the desired target. This study began with the synthesis of the conjugate of 198AuNp-PAMAM G4-nimotuzumab and then tested the clirens and analyzed the results of urine and mouse feces that had been injected with conjugate. Total clearance was obtained about 47.38% of the 198AuNP-PAMAM G4-Nimotuzumab conjugates that have been excreted through urine (18.26%) and stool (29.11%.). Urine and feces were analyzed with SDS-PAGE giving the spot above the 150 kDa band and showing the conjugate molecular weight. FTIR analysis of urine and feces by showing aldehyde functional groups (C = O), alcoholic groups (O-H), amine groups (C-N), and amine groups (N-H) indicating the presence of AuNP-PAMAM G4-Nimotuzumab conjugates in urine and mouse feces. The results of urine and fecal excretion of the conjugate are still conjugate-shaped supported by SDS PAGE analysis, UV-Vis spectrophotometer absorption analysis and functional group analysis with FTIR that has been conducted.


Keywords


gold nanoparticle, PAMAM, nimotuzumab, theranostic agent, clearance

Full Text:

PDF

References


Ahmed, N., Fessi, H., & Elaissari, A., 2012, Theranostic applications of nanoparticles in cancer. Drug Discovery Today, 17(17-18), 928–934. http://doi.org/10.1016/j.drudis.2012.03.010

Barraza, L. F., Jiménez, Verónica A., & Alderete, Joel B., 2015, Effect of PEGylation on the Structure and Drug Loading Capacity of PAMAM-G4 Dendrimers: A Molecular Modeling Approach on the Complexation of 5-Fluorouracil with Native and PEGylated PAMAM-G4, Journal Macromolecular Chemistry and Physics, DOI: 10.1002/macp.201500179.

Gunawan, A. H., Pujianto, A., Maskur, Herlan S. & Rien R., 2014, Karakterisasi Senyawa Pengkontras Ct-Scan Terarah Aunp-PAMAM G4-Nimotuzumab Melalui Simulasi Menggunakan 198AuNP-PAMAM G4-Nimotuzumab, Jurnal Sains Materi Indonesia. Vol. 16, No. 1. ISSN: 1411-1098.

Gunawan, A. H., Pujianto, A., Mutalib, A., S. A. Rista, L. Indrariani, R. Rien, Y. M. Iyus, S. Herlan,

Herlan Setiawan, Anung Pujiyanto, Hotman Lubis, Mujinah, Dede Kurniasih, H., & Rien Ritawidya, A. M, (2012, Pembuatan Larutan H 198AuCl4 Dari Logam Emas, Prosiding Pertemuan Dan Presentasi Ilmiah - Penelitian Dasar Ilmu Pengetahuan Dan Teknologi Nuklir, (ISSN 0216 - 3128), 1–7.

Humani, T. S., Martoprawiro, M. A., & Mutalib, A., 2015, Temperature and Stretching Effects on Complementarity Determining Regions ( CDRs ) Conformation and Stability of Nimotuzumab F(ab) -Fragment, 41(1), 17–25. http://doi.org/10.17146/aij.2015.351

Nanjwade, B. K., Bechra, H. M., Derkar, G. K., Manvi, F. V, & Nanjwade, V. K, 2009, Dendrimers : Emerging polymers for drug-delivery systems, European Journal of Pharmaceutical Sciences, 38, http://doi.org/10.1016/j.ejps.2009.07.008

Ramli, M., Hidayat, B., Rustendi, C. T., Subur, M., Ardiyatno, C. N., Karyadi, K., … Masjhur, J. S, 2012, In Vitro and In Vivo Testing of 177Lu-DOTA-Nimotuzumab, a Potential Radioimmunotherapeutical Agent of Cancers. ITB Journal of Sciences, 44(4), 333–345. http://doi.org/10.5614/itbj.sci.2012.44.4.4

Sutriyo, Mutalib, A., Ristaniah, Anwar, E., Radji, M., Pujiyanto, A., … Adang, H. G, 2015, Synthesis of Gold Nanoparticles with Polyamidoamine (PAMAM) Generation 4 Dendrimer as Stabilizing Agent for CT Scan Contrast Agent. Macromolecular Symposia, 353(1), 96–101. http://doi.org/10.1002/masy.201550312

Sutriyo,Mutalib, A., Ristaniah, Anwar, E., Radji, M., Pujiyanto, A., … Adang, H. G2016, Profil Distribusi dan Klirens Pengkontras CT SCAN AuNP-PAMAM G4-Nimotuzumab disimulasikan menggunakan Senyawa 198AuNP-PAMAM G4-Nimotuzumab, J.Kim.Terap.Indonesia., 18(1). e-ISSN: 2527–7669

Sutriyo, 2015, Pembuatan dan Karakterisasi Konjugat Nanopartikel Emas Radioaktif(198Au)-Densrimer Poliamidoamin Generasi 4-Nimotuzumab Sebagai Agen Theranostic. Disertasi. Universitas Indonesia




DOI: http://dx.doi.org/10.12928/pharmaciana.v7i2.6725

Refbacks

  • There are currently no refbacks.


Copyright (c) 2017 Pharmaciana

---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Pharmaciana indexed by:

Google ScholarDirectory of Open Access JournalIndonesian Scientific Journal Database (ISJD)Indonesian Publication Index (IPI)CrossrefBielefeld Academic Search Engine (BASE)Sherpa RomeoOpen Academic Journal Index (OAJI)

 

 

 

-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------