EDA Çekirdekli Amin, TRIS ve Karboksil Sonlu PAMAM Dendrimerleri Kullanarak Ketoprofenin Çözünürlüğünü Geliştirme

Steroid olmayan antienflamatuar (NSAİ) ilaçlar ağrı kesici, ateş düşürücü ve antiinflamatuar etkilerinden dolayı yaygın bir şekilde kullanılmaktadırlar. Son yıllarda NSAİ ilaçların iyi bilinen klasik etkilerinin yanında birçok farklı terapötik etkilerinin (kanser, Alzheimer ve Parkinson hastalıkları) de bulunduğu keşfedilmiştir. Sonuçlar gösteriyor ki, poli(amidoamin) (PAMAM) dendrimerler varlığında ketoprofen’in (KETO) sudaki çözünürlüğü jenerasyon büyüklüğü (E2-E4) ve dendrimer konsantrasyonun (0-2 mM) artmasıyla önemli ölçüde geliştirilmiştir. KETO’nun (0.22 ± 0.003 mg/mL) çözünürlüğünü arttırmada PAMAM dendrimerlerin rolü E4.TRIS (52.77 ± 2.06 mg/mL)> E4.COOH (36.42 ± 0.54 mg/mL)> E3.TRIS (13.70 ± 0.17 mg/mL)> E3.COOH (11.97 ± 0.14 mg/mL)> E4.NH2 (6.53 ± 0.19 mg/mL)> E2.COOH (5.95 ± 0.10 mg/mL)> E2.TRIS (5.72 ± 0.10 mg/mL)> E3.NH2 (4.21 ± 0.04 mg/mL)> E2.NH2 (2.35 ± 0.04 mg/mL) sırasına göre ve 0.002 M dendrimer varlığında 11 ile 240 kat aralığındadır.

Anahtar Kelimeler:

Dendrimer, Poli(amidoamine) PAMAM; İlaç taşıyıcı; Ketoprofen

PDF

___

[1] Griffin, M.R. 1998. Epidemiology of Nonsteroidal Anti-Inflammatory Drug-Associated Gastrointestinal Injury. The American Journal of Medicine, 104(1998), 23-29.
[2] Chan, T.A. 2002. Nonsteroidal Anti-Inflammatory Drugs, Apoptosis, and Colon-Cancer Chemoprevention. The Lancet Oncology, 3(2002), 166-174.
[3] Polisson, R. 1996. Nonsteroidal Anti-Inflammatory Drugs: Practical and Theoretical Considerations in Their Selection. The American Journal of Medicine, 100(1996), 31S-36S.
[4] Fujii, M., Hori, N., Shiozawa, K., Wakabayashi, K., Kawahara, E., Matsumoto, M. 2000. Effect of Fatty Acid Esters on Permeation of Ketoprofen Through Hairless Rat Skin. International Journal of Pharmaceutics, 205(2000), 117-125.
[5] Vergote, G.J., Vervaet, C., Van Driessche, I., Hoste, S., De Smedt, S., Demeester, J., Jain, R.A., Ruddy, S., Remon, J.P. 2001. An Oral Controlled Release Matrix Pellet Formulation Containing Nanocrystalline Ketoprofen. International Journal of Pharmaceutics, 219(2001), 81-87.
[6] Beezer, A., King, A., Martin, I., Mitchel, J., Twyman, L., Wain, C. 2003. Dendrimers as Potential Drug Carriers; Encapsulation of Acidic Hydrophobes Within Water Soluble PAMAM Derivatives. Tetrahedron, 59(2003), 3873-3880.
[7] Felice, B., Prabhakaran, M.P., Rodríguez, A.P., Ramakrishna, S. 2014. Drug Delivery Vehicles on A Nano-Engineering Perspective. Materials Science and Engineering: C, 41(2014), 178-195.
[8] Sahoo, S.K., Dilnawaz, F., Krishnakumar, S. 2008. Nanotechnology in Ocular Drug Delivery. Drug Discovery Today, 13(2008), 144-151.
[9] Vandamme, T.F., Brobeck, L. 2005. Poly (amidoamine) Dendrimers as Ophthalmic Vehicles for Ocular Delivery of Pilocarpine Nitrate and Tropicamide. Journal of Controlled Release, 102(2005), 23-38.
[10] Fox, M.E., Szoka, F.C., Fréchet, J.M.J. 2009. Soluble Polymer Carriers for the Treatment of Cancer: The Importance of Molecular Architecture. Accounts of Chemical Research, 42(2009), 1141-1151.
[11] Jia, L., Xu, J.P., Wang, H., Ji, J. 2011. Polyamidoamine Dendrimers Surface-Engineered with Biomimetic Phosphorylcholine as Potential Drug Delivery Carriers. Colloids and Surfaces B-Biointerfaces, 84(2011), 49-54.
[12] Malik, N., Wiwattanapatapee, R., Klopsch, R., Lorenz, K., Frey, H., Weener, J.W., Meijer, E.W., Paulus, W., Duncan, R. 2000. Dendrimers: Relationship Between Structure and Biocompatibility in Vitro, and Preliminary Studies on the Biodistribution of 125I-Labelled Polyamidoamine Dendrimers in Vivo. Journal of Controlled Release, 65(2000), 133-148.
[13] Rai, A.K., Tiwari, R., Maurya, P., Yadav, P. 2016. Dendrimers: A Potential Carrier for Targeted Drug Delivery System. Pharmaceutical and Biological Evaluations, 3(2016), 275-287.
[14] Mignani, S., Kazzouli, S.A., Bousmina, M., Majoral, J.P. 2013. Expand Classical Drug Administration Ways by Emerging Routes Using Dendrimer Drug Delivery Systems: A Concise Overview. Advanced Drug Delivery Reviews, 65(2013), 1316-1330.
[15] Kesharwani, P., Jain, K., Jain, N.K. 2014. Dendrimer as Nanocarrier for Drug Delivery. Progress in Polymer Science, 39(2014), 268-307.
[16] Devarakonda, B., Li, N., de Villiers, M.M. 2005. Effect of Polyamidoamine (PAMAM) Dendrimers on The in Vitro Release of Water-Insoluble Nifedipine from Aqueous Gels. AAPS PharmSciTech, 6(2005), E504-E512.
[17] Devarakonda, B., Hill, R.A., Liebenberg, W., Brits, M., de Villiers, M.M. 2005. Comparison of The Aqueous Solubilization of Practically Insoluble Niclosamide by Polyamidoamine (PAMAM) Dendrimers and Cyclodextrins. International Journal of Pharmaceutics, 304(2005), 193-209.
[18] Devarakonda, B., Hill, R., Devilliers, M. 2004. The Effect of PAMAM Dendrimer Generation Size and Surface Functional Group on The Aqueous Solubility of Nifedipine. International Journal of Pharmaceutics, 284(2004), 133-140.
[19] Yiyun, C., Tongwen, X., Rongqiang, F. 2005. Polyamidoamine Dendrimers Used as Solubility Enhancers of Ketoprofen. European Journal of Medicinal Chemistry, 40(2005), 1390-1393.
[20] Ke, W., Zhao, Y., Huang, R., Jiang, C., Pei, Y. 2008. Enhanced Oral Bioavailability of Doxorubicin in A Dendrimer Drug Delivery System. Journal of Pharmaceutical Sciences, 97(2008), 2208-2216.
[21] Ertürk, A.S., Gürbüz, M.U., Tülü, M. 2017. The Effect of PAMAM Dendrimer Concentration, Generation Size and Surface Functional Group on The Aqueous Solubility of Candesartan Cilexetil. Pharmaceutical Development and Technology, 22(2017), 111-121.
[22] Mecke, A., Majoros, I.J., Patri, A.K., Baker, J.R., Banaszak Holl, M.M., Orr, B.G., 2005. Lipid Bilayer Disruption by Polycationic Polymers: The Roles of Size and Chemical Functional Group. Langmuir, 21(2005), 10348-10354.
[23] Duncan, R., Izzo, L. 2005. Dendrimer Biocompatibility and Toxicity. Advanced Drug Delivery Reviews, 57(2005), 2215-2237.
[24] Twyman, L.J., Beezer, A.E., Esfand, R., Hardy, M.J., Mitchell, J.C. 1999. The Synthesis of Water Soluble Dendrimers, and Their Application as Possible Drug Delivery Systems. Tetrahedron Letters, 40(1999), 1743-1746.
[25] Ertürk, A.S., Gürbüz, M.U., Tülü, M. 2017. New-generation Jeffamine® D230 Core Amine, TRIS and Carboxyl-Terminated PAMAM Dendrimers: Synthesis, Characterization and The Solubility Application for A Model NSAID Drug Ibuprofen. Marmara Pharmaceutical Journal, 21(2017), 385-399.
[26] Gürbüz, M.U., Ertürk, A.S., Tülü, M. 2016. Synthesis of Surface-Modified TREN-Cored PAMAM Dendrimers and Their Effects on The Solubility of Sulfamethoxazole (SMZ) as An Analog Antibiotic Drug. Pharmaceutical Development and Technology, 2016), 1-12.
[27] Chauhan, A.S., Jain, N.K., Diwan, P.V., Khopade, A.J. 2004. Solubility Enhancement of Indomethacin with Poly(amidoamine) Dendrimers and Targeting to Inflammatory Regions of Arthritic Rats. Journal Drug Targeting, 12(2004), 575-583.
[28] Silion, M., Hritcu, D., Popa, M. 2010. Preparation and Characterization of Ketoprofen-Layered Double Hydroxide Compounds. Journal of Optoelectronics and Advanced Materials, 12(2010), 2151-2157.
[29] Popescu, M.C., Filip, D., Vasile, C., Cruz, C., Rueff, J., Marcos, M., Serrano, J., Singurel, G. 2006. Characterization by Fourier Transform Infrared Spectroscopy (FT-IR) and 2D IR Correlation Spectroscopy of PAMAM Dendrimer. The Journal of Physical Chemistry B, 110(2006), 14198-14211.
[30] Singh, P., Gupta, U., Asthana, A., Jain, N.K. 2008. Folate and folate− PEG− PAMAM Dendrimers: Synthesis, Characterization, and Targeted Anticancer Drug Delivery Potential in Tumor Bearing Mice. Bioconjugate Chemistry, 19(2008), 2239-2252.
[31] Latere Dwan'Isa, J.P., Rouxhet, L., Preat, V., Brewster, M., Arien, A. 2007. Prediction of Drug Solubility in Amphiphilic Di-Block Copolymer Micelles: The Role of Polymer-Drug Compatibility. Die Pharmazie-An International Journal of Pharmaceutical Sciences, 62(2007), 499-504.
[32] Jain, S., Kaur, A., Puri, R., Utreja, P., Jain, A., Bhide, M., Ratnam, R., Singh, V., Patil, A., Jayaraman, N. 2010. Poly Propyl Ether Imine (PETIM) Dendrimer: A Novel Non-Toxic Dendrimer for Sustained Drug Delivery. European Journal of Medicinal Chemistry, 45(2010), 4997-5005.