Abstract
Sterically stabilized micelle (SSM) is a self-assembled nanoparticle ideal for the delivery of therapeutic peptides. The PEGylated phospholipid forming the particle, DSPE-PEG2000, is a safe, biocompatible, and biodegradable ingredient already approved for human use in the marketed product Doxil®. SSM can overcome formulation difficulties such as instability associated with peptide drugs, enabling their development for clinical application. The key advantage of this lipid-based nanocarrier is its simple preparation even at large scales, which allows easy transition to the clinics and the pharmaceutical market. In this chapter, we describe methods for preparation and characterization of peptides self-associated with SSM (peptide–SSM). We also discuss approaches to evaluate the biological activity of the peptide nanomedicines in vitro and in vivo.
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References
Craik DJ, Fairlie DP, Liras S, Price D (2013) The future of peptide-based drugs. Chem Biol Drug Des 81(1):136–147
Fosgerau K, Hoffmann T (2015) Peptide therapeutics: current status and future directions. Drug Discov Today 20(1):122–128
Vukovic L, Khatib FA, Drake SP, Madriaga A, Brandenburg KS, Král P, Onyuksel H (2011) Structure and dynamics of highly PEG-ylated sterically stabilized micelles in aqueous media. J Am Chem Soc 133(34):13481–13488
Ashok B, Arleth L, Hjelm RP, Rubinstein I, Önyüksel H (2004) In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization: effects of PEG chain length and PC incorporation. J Pharm Sci 93(10):2476–2487
Banerjee A, Onyuksel H (2012) Peptide delivery using phospholipid micelles. Wiley Interdiscip Rev Nanomed Nanobiotechnol 4(5):562–574
Lim SB, Banerjee A, Önyüksel H (2012) Improvement of drug safety by the use of lipid-based nanocarriers. J Control Release 163(1):34–45
Sethi V, Rubinstein I, Kuzmis A, Kastrissios H, Artwohl J, Onyuksel H (2013) Novel, biocompatible, and disease modifying VIP nanomedicine for rheumatoid arthritis. Mol Pharm 10(2):728–738
Khaja FA, Koo O, Onyuksel H (2012) Nanomedicines for inflammatory diseases. Methods Enzymol 508:355–375
Bak A, Leung D, Barrett SE, Forster S, Minnihan EC, Leithead AW, Cunningham J, Toussaint N, Crocker LS (2015) Physicochemical and formulation developability assessment for therapeutic peptide delivery—a primer. AAPS J 17(1):144–155
Vuković L, Madriaga A, Kuzmis A, Banerjee A, Tang A, Tao K, Shah N, Král P, Onyuksel H (2013) Solubilization of therapeutic agents in micellar nanomedicines. Langmuir 29(51):15747–15754
Krishnadas A, Onyuksel H, Rubinstein I (2003) Interactions of VIP, secretin and PACAP1–38 with phospholipids: a biological paradox revisited. Curr Pharm Des 9(12):1005–1012
Yuan Z, Syed M, Panchal D, Joo M, Bedi C, Lim S, Onyuksel H, Rubinstein I, Colonna M, Sadikot RT (2016) TREM-1-accentuated lung injury via miR-155 is inhibited by LP17 nanomedicine. Am J Physiol Lung Cell Mol Physiol 310(5):L426–L438
Gandhi S, Rubinstein I, Tsueshita T, Onyuksel H (2002) Secretin self-assembles and interacts spontaneously with phospholipids in vitro. Peptides 23(1):201–204
Gandhi S, Tsueshita T, Önyüksel H, Chandiwala R, Rubinstein I (2002) Interactions of human secretin with sterically stabilized phospholipid micelles amplify peptide-induced vasodilation in vivo. Peptides 23(8):1433–1439
Önyüksel H, Ikezaki H, Patel M, Gao X-P, Rubinstein I (1999) A novel formulation of VIP in sterically stabilized micelles amplifies vasodilation in vivo. Pharm Res 16(1):155–160
Lim SB, Rubinstein I, Önyüksel H (2008) Freeze drying of peptide drugs self-associated with long-circulating, biocompatible and biodegradable sterically stabilized phospholipid nanomicelles. Int J Pharm 356(1):345–350
Lim SB, Rubinstein I, Sadikot RT, Artwohl JE, Önyüksel H (2011) A novel peptide nanomedicine against acute lung injury: GLP-1 in phospholipid micelles. Pharm Res 28(3):662–672
Anbazhagan AN, Thaqi M, Priyamvada S, Jayawardena D, Kumar A, Gujral T, Chatterjee I, Mugarza E, Saksena S, Onyuksel H (2017) GLP-1 nanomedicine alleviates gut inflammation. Nanomedicine 13(2):659–665
Kuzmis A, Lim SB, Desai E, Jeon E, Lee B-S, Rubinstein I, Önyüksel H (2011) Micellar nanomedicine of human neuropeptide Y. Nanomedicine 7(4):464–471
Banerjee A, Onyuksel H (2012) Human pancreatic polypeptide in a phospholipid-based micellar formulation. Pharm Res 29(6):1698–1711
Banerjee A, Onyuksel H (2013) A novel peptide nanomedicine for treatment of pancreatogenic diabetes. Nanomedicine 9(6):722–728
Tsueshita T, Gandhi S, Önyüksel H, Rubinstein I (2002) Phospholipids modulate the biophysical properties and vasoactivity of PACAP-(1—38). J Appl Physiol 93(4):1377–1383
Rubinstein I, Lim SB, Jeon E, Onyuksel H (2007) Human GLP-1 {alpha} and GIP {alpha}: novel, long-acting nanomedicines for type II diabetes mellitus. FASEB J 21(5):A434
Kaszuba M, McKnight D, Connah MT, McNeil-Watson FK, Nobbmann U (2008) Measuring sub nanometre sizes using dynamic light scattering. J Nanopart Res 10(5):823–829
Chung LA, Lear JD, DeGrado WF (1992) Fluorescence studies of the secondary structure and orientation of a model ion channel peptide in phospholipid vesicles. Biochemistry 31(28):6608–6616
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Esparza, K., Jayawardena, D., Onyuksel, H. (2019). Phospholipid Micelles for Peptide Drug Delivery. In: Weissig, V., Elbayoumi, T. (eds) Pharmaceutical Nanotechnology. Methods in Molecular Biology, vol 2000. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9516-5_4
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DOI: https://doi.org/10.1007/978-1-4939-9516-5_4
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