Year 2022,
, 107 - 118, 25.03.2022
Selen Isar
,
Hüseyin Yiğit Şahin
,
Hasan Akbaba
,
Ayşe Nalbantsoy
,
Gülşah Erel Akbaba
,
Yücel Başpınar
References
- [1]. Rolland, A, Sullivan, SM. Mechanisms for Cationic Lipids in Gene Transfer. Pharm Gene Del Sys, Eastern Hemisphere Distribution, New York 2003.
- [2]. Taira, K, Kataoka, TN (Eds.). Non-Viral Gene Therapy. Gene Design and Delivery. Springer-Verlag, Tokyo 2005.
- [3]. Clement, J, Kiefer, K, Kimpfler, A, Garidel, P, Peschka-Suss, R. 2005. Large-scale production of lipoplexes with long shelf-life. European Journal of Pharmaceutics and Biopharmaceutics; 59: 35–43.
- [4]. Kawakami, S, Higuchi, Y, Hashida, M. 2008. Nonviral approaches for targeted delivery of plasmid DNA and oligonucleotide. Journal of Pharmaceutical Sciences; 97: 726–745.
- [5]. Schuh, R, Baldo, G, Teixeira, H. 2016. Nanotechnology applied to treatment of mucopolysaccharidoses. Expert Opinion on Drug Delivery; 13: 1709–1718.
- [6]. Verissimo, LM, Lima, LFA, Egito, LCM, de Oliveira, AG, do Egito, EST. 2010. Pharmaceutical emulsions: a new approach for gene therapy. Journal of Drug Targeting; 18: 333–342.
- [7]. Wasungu, L, Hoekstra, D. 2006. Cationic lipids, lipoplexes and intracellular delivery of genes. Journal of Controlled Release; 116: 255–264.
- [8]. Hara, T, Liu, F, Liu, D, Huang, L. 1997. Emulsion formulations as a vector for gene delivery in vitro and in vivo. Advanced Drug Delivery Reviews; 24:265-271.
- [9]. Liu, F, Yang, J, Huang, L, Liu, D. 1996. Effect of non-ionic surfactants on the formation of DNA/emulsion complexes and emulsion-mediated gene transfer. Pharmaceutical Research; 13: 1642-1646.
- [10]. Teixeira, H, Dubernet, C, Puisieux, F, Benita, S, Couvreur, P. 1999. Submicron cationic emulsions as a new delivery system for oligonucleotides. Pharmaceutical Research; 16: 30–36.
- [11]. Zhang, S, Xu, Y, Wang, B, Qiao, W, Liu, D, Li, Z. 2004. Cationic compounds used in lipoplexes and polyplexes for gene delivery. Journal of Controlled Release; 100: 165–180.
- [12]. Pavicic, T, Wollenweber, U, Farwick, M, Korting, H.C. 2007. Anti-microbial and -inflammatory activity and efficacy of phytosphingosine: an in vitro and in vivo study addressing acne vulgaris, International Journal of Cosmetic Science; 29: 181–190.
- [13]. Castro, A, Lemos, C, Falcao, A, Glass, NL, Videira, A. 2008. Increased Resistance of Complex I Mutants to Phytosphingosine-induced Programmed Cell Death. The Journal of Biological Chemistry; 283 (28), 19314–19321.
- [14]. Simbulan, CM, Tamiya-Koizumi, K, Suzuki, M, Shoji, M, Taki, T. 1994. Yoshida S. Sphingosine inhibits the synthesis of RNA primers by primase in vitro. Biochemistry; 33: 9007–12.
- [15]. Hung, WC, Chang, HC, Chuang, LY. 1999. Activation of caspase-3-like proteases in apoptosis induced by sphingosine and other long-chain bases in Hep3B hepatoma cells. Biochemical Journal; 338: 161–6.
- [16]. Gottlob, K, Majewski, N, Kennedy, S, Kandel, E, Robey, RB, Hay, N. 2001. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes & Development; 15: 1406–18.
- [17]. Nagahara, Y, Shinomiya, T, Kuroda, S, Kaneko, N, Nishio, R, Ikekit, M. 2005. Phytosphingosine induced mitochondria-involved apoptosis. Cancer Science; 96: 83–92.
- [18]. Park, MT, Choi, JA, Kim, MJ, Um, HD, Bae, S, Kang, CM, Cho, CK, Kang, S, Chung, SY, Lee, YS, Lee, SJ. 2003a. Suppression of Extracellular Signal-related Kinase and Activation of p38 MAPK Are Two Critical Events Leading to Caspase-8- and Mitochondria-mediated Cell Death in Phytosphingosine-treated Human Cancer Cells. Journal of Biological Chemistry; 278: 50624–50634.
- [19]. Park MT, Kang JA, Choi JA, Kang CM, Kim TH, Bae S, Kang S, Kim S, Choi WI, Cho CK, Chung HY, Lee YS, Lee SJ. 2003b. Phytosphingosine Induces Apoptotic Cell Death via Caspase 8 Activation and Bax Translocation in Human Cancer Cells. Clinical Cancer Research; 9: 878–885.
- [20]. Baspinar, Y., Keck, C. Borchert, HH. 2010. Development of a positively charged prednicarbate nanoemulsion. International Journal of Pharmaceutics; 383 (1-2) 201-208.
- [21]. Baspinar, Y, Borchert HH. 2012. Penetration and release studies of positively and negatively charged nanoemulsions—Is there a benefit of the positive charge? International Journal of Pharmaceutics; 430:247– 252.
- [22]. Başpınar, Y, Gündoğdu, E, Köksal, C, Karasulu, E. 2015. Pitavastatin-containing nanoemulsions: Preparation, characterization and in vitro cytotoxicity. Journal of Drug Delivery Science and Technology; 29, 117-124.
- [23]. Isar, S, Akbaba, H, Erel-Akbaba, H, Başpınar, Y. 2020. Development and characterization of cationic nanoemulsions as non-viral vectors for plasmid DNA delivery. Journal of Research in Pharmacy, 24(6), 952-960.
- [24]. Başpınar, Y, Gündoğdu, E, Karasulu, E, Borchert, HH. 2013. The preparation of prednicarbate nanoemulsions - a comparison of three homogenizers. Nano-Bulletin; 2: 130102.
- [25]. Muller, RH. Zetapotential und Partikeladung in der Laborpraxis,Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, 1996.
- [26]. Akbaba, H, Erel Akbaba, G, Kantarcı, AG. 2018. Development and evaluation of antisense shRNA-encoding plasmid loaded solid lipid nanoparticles against 5-α reductase activity. Journal of Drug Delivery, Science and Technology; 44: 270–277.
- [27]. Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods; 65; 55-63,
- [28]. Nalbantsoy, A,, Hempel, BF, Petras, D, Heiss, P, Göçmen, B, Iğci, N, Yildiz, MZ, Süssmuth, RD. 2017. Combined venom profiling and cytotoxicity screening of the Radde's mountain viper (Montivipera raddei) and Mount Bulgar Viper (Montivipera bulgardaghica) with potent cytotoxicity against human A549 lung carcinoma cells. Toxicon; 135; 71-83.
- [29]. Baspinar, Y. 2009. Nano-and microemulsions for topical application of poorly soluble immunosuppressives
Long-term Stability of Cationic Phytosphingosine Nanoemulsions as Delivery Systems for plasmid DNA
Year 2022,
, 107 - 118, 25.03.2022
Selen Isar
,
Hüseyin Yiğit Şahin
,
Hasan Akbaba
,
Ayşe Nalbantsoy
,
Gülşah Erel Akbaba
,
Yücel Başpınar
Abstract
The case of ready to use gene delivery systems like cationic nanoemulsions is not reflecting the truth. Thus, delivery systems for applicating genes like nucleic acids have to be prepared freshly before each application. This study is focused on the preparation and characterization of cationic nanoemulsions using phytosphingosine for plasmid DNA delivery. Repurposing of cationic agents guided us to phytosphingosine, previously used for enhanced interaction with negatively charged surfaces. It was reported that phytosphingosine may act anti-apoptotic, but without using it in an appropriate delivery system like nanoemulsions. This gap attracted our interest about preparing and characterizing long-term stable cationic nanoemulsions and their cytotoxic effects on MDA-MB-231 and MCF-7 breast cancer cells using phytosphingosine. The cationic nanoemulsions 1, 2, and 3 were prepared and characterized in terms of droplet size, polydispersity index, and zeta potential, long-term stability after storage at 25 and 40 °C, complexation with pDNA, release and cytotoxicity on MDA-MB-231 and MCF-7 cells. The CNEs showed appropriate properties like a small droplet size (<200 nm), a narrow size distribution and a high zeta potential (>+30 mV). Unfortunately, each cationic nanoemulsion showed some disadvantages. Cationic nanoemulsion 1 decreased the viability of cancer cells to only 25 %. Phase separation was observed for cationic nanoemulsion 2 after storage of six months at 40 °C. And cationic nanoemulsion 3 was not able to form a complex with pDNA.
However, cationic nanoemulsion 1 is more appropriate than the other cationic nanoemulsions for delivering pDNA.
References
- [1]. Rolland, A, Sullivan, SM. Mechanisms for Cationic Lipids in Gene Transfer. Pharm Gene Del Sys, Eastern Hemisphere Distribution, New York 2003.
- [2]. Taira, K, Kataoka, TN (Eds.). Non-Viral Gene Therapy. Gene Design and Delivery. Springer-Verlag, Tokyo 2005.
- [3]. Clement, J, Kiefer, K, Kimpfler, A, Garidel, P, Peschka-Suss, R. 2005. Large-scale production of lipoplexes with long shelf-life. European Journal of Pharmaceutics and Biopharmaceutics; 59: 35–43.
- [4]. Kawakami, S, Higuchi, Y, Hashida, M. 2008. Nonviral approaches for targeted delivery of plasmid DNA and oligonucleotide. Journal of Pharmaceutical Sciences; 97: 726–745.
- [5]. Schuh, R, Baldo, G, Teixeira, H. 2016. Nanotechnology applied to treatment of mucopolysaccharidoses. Expert Opinion on Drug Delivery; 13: 1709–1718.
- [6]. Verissimo, LM, Lima, LFA, Egito, LCM, de Oliveira, AG, do Egito, EST. 2010. Pharmaceutical emulsions: a new approach for gene therapy. Journal of Drug Targeting; 18: 333–342.
- [7]. Wasungu, L, Hoekstra, D. 2006. Cationic lipids, lipoplexes and intracellular delivery of genes. Journal of Controlled Release; 116: 255–264.
- [8]. Hara, T, Liu, F, Liu, D, Huang, L. 1997. Emulsion formulations as a vector for gene delivery in vitro and in vivo. Advanced Drug Delivery Reviews; 24:265-271.
- [9]. Liu, F, Yang, J, Huang, L, Liu, D. 1996. Effect of non-ionic surfactants on the formation of DNA/emulsion complexes and emulsion-mediated gene transfer. Pharmaceutical Research; 13: 1642-1646.
- [10]. Teixeira, H, Dubernet, C, Puisieux, F, Benita, S, Couvreur, P. 1999. Submicron cationic emulsions as a new delivery system for oligonucleotides. Pharmaceutical Research; 16: 30–36.
- [11]. Zhang, S, Xu, Y, Wang, B, Qiao, W, Liu, D, Li, Z. 2004. Cationic compounds used in lipoplexes and polyplexes for gene delivery. Journal of Controlled Release; 100: 165–180.
- [12]. Pavicic, T, Wollenweber, U, Farwick, M, Korting, H.C. 2007. Anti-microbial and -inflammatory activity and efficacy of phytosphingosine: an in vitro and in vivo study addressing acne vulgaris, International Journal of Cosmetic Science; 29: 181–190.
- [13]. Castro, A, Lemos, C, Falcao, A, Glass, NL, Videira, A. 2008. Increased Resistance of Complex I Mutants to Phytosphingosine-induced Programmed Cell Death. The Journal of Biological Chemistry; 283 (28), 19314–19321.
- [14]. Simbulan, CM, Tamiya-Koizumi, K, Suzuki, M, Shoji, M, Taki, T. 1994. Yoshida S. Sphingosine inhibits the synthesis of RNA primers by primase in vitro. Biochemistry; 33: 9007–12.
- [15]. Hung, WC, Chang, HC, Chuang, LY. 1999. Activation of caspase-3-like proteases in apoptosis induced by sphingosine and other long-chain bases in Hep3B hepatoma cells. Biochemical Journal; 338: 161–6.
- [16]. Gottlob, K, Majewski, N, Kennedy, S, Kandel, E, Robey, RB, Hay, N. 2001. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes & Development; 15: 1406–18.
- [17]. Nagahara, Y, Shinomiya, T, Kuroda, S, Kaneko, N, Nishio, R, Ikekit, M. 2005. Phytosphingosine induced mitochondria-involved apoptosis. Cancer Science; 96: 83–92.
- [18]. Park, MT, Choi, JA, Kim, MJ, Um, HD, Bae, S, Kang, CM, Cho, CK, Kang, S, Chung, SY, Lee, YS, Lee, SJ. 2003a. Suppression of Extracellular Signal-related Kinase and Activation of p38 MAPK Are Two Critical Events Leading to Caspase-8- and Mitochondria-mediated Cell Death in Phytosphingosine-treated Human Cancer Cells. Journal of Biological Chemistry; 278: 50624–50634.
- [19]. Park MT, Kang JA, Choi JA, Kang CM, Kim TH, Bae S, Kang S, Kim S, Choi WI, Cho CK, Chung HY, Lee YS, Lee SJ. 2003b. Phytosphingosine Induces Apoptotic Cell Death via Caspase 8 Activation and Bax Translocation in Human Cancer Cells. Clinical Cancer Research; 9: 878–885.
- [20]. Baspinar, Y., Keck, C. Borchert, HH. 2010. Development of a positively charged prednicarbate nanoemulsion. International Journal of Pharmaceutics; 383 (1-2) 201-208.
- [21]. Baspinar, Y, Borchert HH. 2012. Penetration and release studies of positively and negatively charged nanoemulsions—Is there a benefit of the positive charge? International Journal of Pharmaceutics; 430:247– 252.
- [22]. Başpınar, Y, Gündoğdu, E, Köksal, C, Karasulu, E. 2015. Pitavastatin-containing nanoemulsions: Preparation, characterization and in vitro cytotoxicity. Journal of Drug Delivery Science and Technology; 29, 117-124.
- [23]. Isar, S, Akbaba, H, Erel-Akbaba, H, Başpınar, Y. 2020. Development and characterization of cationic nanoemulsions as non-viral vectors for plasmid DNA delivery. Journal of Research in Pharmacy, 24(6), 952-960.
- [24]. Başpınar, Y, Gündoğdu, E, Karasulu, E, Borchert, HH. 2013. The preparation of prednicarbate nanoemulsions - a comparison of three homogenizers. Nano-Bulletin; 2: 130102.
- [25]. Muller, RH. Zetapotential und Partikeladung in der Laborpraxis,Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, 1996.
- [26]. Akbaba, H, Erel Akbaba, G, Kantarcı, AG. 2018. Development and evaluation of antisense shRNA-encoding plasmid loaded solid lipid nanoparticles against 5-α reductase activity. Journal of Drug Delivery, Science and Technology; 44: 270–277.
- [27]. Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. Journal of Immunological Methods; 65; 55-63,
- [28]. Nalbantsoy, A,, Hempel, BF, Petras, D, Heiss, P, Göçmen, B, Iğci, N, Yildiz, MZ, Süssmuth, RD. 2017. Combined venom profiling and cytotoxicity screening of the Radde's mountain viper (Montivipera raddei) and Mount Bulgar Viper (Montivipera bulgardaghica) with potent cytotoxicity against human A549 lung carcinoma cells. Toxicon; 135; 71-83.
- [29]. Baspinar, Y. 2009. Nano-and microemulsions for topical application of poorly soluble immunosuppressives