Abstract
Lipid-based vesicles, namely cationic liposomal nanocarriers have been recognized early on as one of the most attractive delivery systems for RNA, protein, and oligonucleotides. Despite several advantages of conventional liposomal carriers for therapeutic macromolecules, their flexible and unsupported bilayered membranes can pose some limitations for efficient intracellular delivery of their sensitive cargos. Hence, polymerized liposomes, a concept conceived about 20 years ago, might offer structural solution to current in vivo efficiency concerns affecting traditional cationic phospholipid vectors, especially when adapted to enable superior loading and stability, typically required for effective intracellular delivery of proteins and polynucleotides.
Our recent approach attempted to remodel polymerized liposomal vesicles—specifically their semi-rigid membrane structure—to create block-polymerized bilayered vesicles (generally composed of DOTAP: DOPE: Diyne PC in 0.1:1:1 molar ratio). Adopting a modified freeze-dry-rehydration technique allowed modular reassembly of such partially polymerized lipidic vesicles (PPL). Different prototype cationic partially polymerized liposomal preparations (PPLs) were successfully developed (mean particle size range 150–300 nm), demonstrating enhanced physicochemical stability and loading capacity, thus promoting improved intracellular delivery of model RNAi and protein cargos.
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References
Santel A, Aleku M, Keil O, Endruschat J, Esche V, Durieux B, Loffler K, Fechtner M, Rohl T, Fisch G, Dames S, Arnold W, Giese K, Klippel A, Kaufmann J (2006) RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy. Gene Ther 13:1360–1370
Nabel GJ, Nabel EG, Yang ZY, Fox BA, Plautz GE, Gao X, Huang L, Shu S, Gordon D, Chang AE (1993) Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans. Proc Natl Acad Sci U S A 90:11307–11311
Gill DR, Southern KW, Mofford KA, Seddon T, Huang L, Sorgi F, Thomson A, MacVinish LJ, Ratcliff R, Bilton D, Lane DJ, Littlewood JM, Webb AK, Middleton PG, Colledge WH, Cuthbert AW, Evans MJ, Higgins CF, Hyde SC (1997) A placebo-controlled study of liposome-mediated gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther 4:199–209
Auguste DT, Furman K, Wong A, Fuller J, Armes SP, Deming TJ, Langer R (2008) Triggered release of siRNA from poly(ethylene glycol)-protected, pH-dependent liposomes. J Control Release 130:266–274
Akinc A, Goldberg M, Qin J, Dorkin JR, Gamba-Vitalo C, Maier M, Jayaprakash KN, Jayaraman M, Rajeev KG, Manoharan M, Koteliansky V, Rohl I, Leshchiner ES, Langer R, Anderson DG (2009) Development of lipidoid-siRNA formulations for systemic delivery to the liver. Mol Ther 17:872–879
Frank-Kamenetsky M, Grefhorst A, Anderson NN, Racie TS, Bramlage B, Akinc A, Butler D, Charisse K, Dorkin R, Fan Y, Gamba-Vitalo C, Hadwiger P, Jayaraman M, John M, Jayaprakash KN, Maier M, Nechev L, Rajeev KG, Read T, Rohl I, Soutschek J, Tan P, Wong J, Wang G, Zimmermann T, de Fougerolles A, Vornlocher HP, Langer R, Anderson DG, Manoharan M, Koteliansky V, Horton JD, Fitzgerald K (2008) Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci U S A 105:11915–11920
Nguyen DN, Chen SC, Lu J, Goldberg M, Kim P, Sprague A, Novobrantseva T, Sherman J, Shulga-Morskaya S, de Fougerolles A, Chen J, Langer R, Anderson DG (2009) Drug delivery-mediated control of RNA immunostimulation. Mol Ther 17:1555–1562
Wu SY, McMillan NA (2009) Lipidic systems for in vivo siRNA delivery. AAPS J 11(4):639–652
Whitehead KA, Langer R, Anderson DG (2009) Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8:129–138
Huang YH, Bao Y, Peng W, Goldberg M, Love K, Bumcrot DA, Cole G, Langer R, Anderson DG, Sawicki JA (2009) Claudin-3 gene silencing with siRNA suppresses ovarian tumor growth and metastasis. Proc Natl Acad Sci U S A 106:3426–3430
Akinc A, Zumbuehl A, Goldberg M, Leshchiner ES, Busini V, Hossain N, Bacallado SA, Nguyen DN, Fuller J, Alvarez R, Borodovsky A, Borland T, Constien R, de Fougerolles A, Dorkin JR, Narayanannair Jayaprakash K, Jayaraman M, John M, Koteliansky V, Manoharan M, Nechev L, Qin J, Racie T, Raitcheva D, Rajeev KG, Sah DW, Soutschek J, Toudjarska I, Vornlocher HP, Zimmermann TS, Langer R, Anderson DG (2008) A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat Biotechnol 26:561–569
Weissmann G, Finkelstein M (1980) Uptake of enzyme-bearing liposomes by cells in vivo and in vitro. In: Gregoriadis G, Allison AC (eds) Liposomes in biological systems. Wiley, New York, NY, pp 153–162
Kirby C, Clarke J, Gregoriadis G (1980) Effect of the cholesterol content of small unilamellar liposomes on their stability in vivo and in vitro. Biochem J 186:591–598
Torchilin VP, Weissig V (2003) Liposomes: a practical approach, 2nd edn. Oxford University Press, Oxford
Chen H, Torchilin V, Langer R (1996) Lectin-bearing polymerized liposomes as potential oral vaccine carriers. Pharm Res 13:1378–1383
Alonso-Romanowski S, Chiaramoni NS, Lioy VS, Gargini RA, Viera LI, Taira MC (2003) Characterization of diacetylenic liposomes as carriers for oral vaccines. Chem Phys Lipids 122:191–203
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Goshi, M., Pytel, N., Elbayoumi, T. (2019). Partially Polymerized Phospholipid Vesicles for Efficient Delivery of Macromolecules. 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_18
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DOI: https://doi.org/10.1007/978-1-4939-9516-5_18
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