Systemic gene delivery using lipid envelope systems and its potential in overcoming challenges

Authors

  • Miteshkumar Malaviya Shree Dhanvantary Pharmacy College Gujarat,394110 India
  • Milankumar Shiroya Shree Dhanvantary Pharmacy College Gujarat,394110 India

DOI:

https://doi.org/10.47957/ijpda.v9i1.458

Keywords:

Lipid envelop, gene delivery, chronic diseases

Abstract

Nonviral vectors which offer a safer and versatile alternative to viral vectors have been developed to overcome problems caused by viral carriers. However, their transfection efficacy or level of expression is substantially lower than viral vectors. Among various nonviral gene vectors, lipid envelops systems are an ideal platform for the incorporation of safety and efficacy into a single delivery system. Emerging strategies for gene delivery using lipid-based delivery systems mainly aim at improving the transfection efficiency and potency while reducing toxicity, achieving prolonged release, cell-specific targeting, co-delivery of drug and gene. Earlier efforts to improve the transfection efficiency while overcoming the toxicity led to the need for preparing conjugates of lipids with polyamines. In this review, we highlight current lipidic vectors that have been developed for gene therapy, challenges, and their solutions.

Downloads

Download data is not yet available.

References

Gogotsi Y. Nanomaterials Handbook: CRC Press; 2006.

Wang J, Lu Z, Wientjes MG, Au JL. Delivery of siRNA therapeutics: barriers and carriers. The AAPS journal. 2010;12(4):492-503.

Werth S, Urban-Klein B, Dai L, Hobel S, Grzelinski M, Bakowsky U, et al. A low molecular weight fraction of polyethylenimine (PEI) displays increased transfection efficiency of DNA and siRNA in fresh or lyophilized complexes. Journal of controlled release : official journal of the Controlled Release Society. 2006;112(2):257-70.

Urban-Klein B, Werth S, Abuharbeid S, Czubayko F, Aigner A. RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene therapy. 2005;12(5):461-6.

Kim WJ, Chang CW, Lee M, Kim SW. Efficient siRNA delivery using water soluble lipopolymer for anti-angiogenic gene therapy. J Control Release. 2007;118(3):357-63.

Song H, Wang G, He B, Li L, Li C, Lai Y, et al. Cationic lipid-coated PEI/DNA polyplexes with improved efficiency and reduced cytotoxicity for gene delivery into mesenchymal stem cells. Int J Nanomedicine. 2012;7:4637-48.

Schäfer J, Höbel S, Bakowsky U, Aigner A. Liposome–polyethylenimine complexes for enhanced DNA and siRNA delivery. Biomaterials. 2010;31(26):6892-900.

Godbey WT, Wu KK, Mikos AG. Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(9):5177-81.

Honore I, Grosse S, Frison N, Favatier F, Monsigny M, Fajac I. Transcription of plasmid DNA: influence of plasmid DNA/polyethylenimine complex formation. Journal of controlled release : official journal of the Controlled Release Society. 2005;107(3):537-46.

Mao S, Neu M, Germershaus O, Merkel O, Sitterberg J, Bakowsky U, et al. Influence of polyethylene glycol chain length on the physicochemical and biological properties of poly(ethylene imine)-graft-poly(ethylene glycol) block copolymer/SiRNA polyplexes. Bioconjugate chemistry. 2006;17(5):1209-18.

Zintchenko A, Philipp A, Dehshahri A, Wagner E. Simple modifications of branched PEI lead to highly efficient siRNA carriers with low toxicity. Bioconjugate chemistry. 2008;19(7):1448-55.

Kunath K, von Harpe A, Fischer D, Kissel T. Galactose-PEI-DNA complexes for targeted gene delivery: degree of substitution affects complex size and transfection efficiency. Journal of controlled release : official journal of the Controlled Release Society. 2003;88(1):159-72.

He W, Guo Z, Wen Y, Wang Q, Xie B, Zhu S. Alginate-graft-PEI as a gene delivery vector with high efficiency and low cytotoxicity. J Biomater Sci Polym Ed. 2012;23(1-4):315-31.

Choi YS, Lee JY, Suh JS, Kwon YM, Lee SJ, Chung JK, et al. The systemic delivery of siRNAs by a cell penetrating peptide, low molecular weight protamine. Biomaterials. 2010;31(6):1429-43.

Moschos SA, Williams AE, Lindsay MA. Cell-penetrating-peptide-mediated siRNA lung delivery. Biochemical Society transactions. 2007;35(Pt 4):807-10.

Youn P, Chen Y, Furgeson DY. A Myristoylated Cell-Penetrating Peptide Bearing a Transferrin Receptor-Targeting Sequence for Neuro-Targeted siRNA Delivery. Mol Pharm. 2014;11(2):486-95.

Kim WJ, Christensen LV, Jo S, Yockman JW, Jeong JH, Kim YH, et al. Cholesteryl oligoarginine delivering vascular endothelial growth factor siRNA effectively inhibits tumor growth in colon adenocarcinoma. Molecular therapy : the journal of the American Society of Gene Therapy. 2006;14(3):343-50.

DeRouchey J, Schmidt C, Walker GF, Koch C, Plank C, Wagner E, et al. Monomolecular assembly of siRNA and poly(ethylene glycol)-peptide copolymers. Biomacromolecules. 2008;9(2):724-32.

Leng Q, Scaria P, Lu P, Woodle MC, Mixson AJ. Systemic delivery of HK Raf-1 siRNA polyplexes inhibits MDA-MB-435 xenografts. Cancer Gene Ther. 2008;15(8):485-95.

Stevenson M, Ramos-Perez V, Singh S, Soliman M, Preece JA, Briggs SS, et al. Delivery of siRNA mediated by histidine-containing reducible polycations. Journal of controlled release : official journal of the Controlled Release Society. 2008;130(1):46-56.

Peer D, Zhu P, Carman CV, Lieberman J, Shimaoka M. Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function-associated antigen-1. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(10):4095-100.

Nakamura Y, Kogure K, Futaki S, Harashima H. Octaarginine-modified multifunctional envelope-type nano device for siRNA. Journal of controlled release : official journal of the Controlled Release Society. 2007;119(3):360-7.

Dassie JP, Liu XY, Thomas GS, Whitaker RM, Thiel KW, Stockdale KR, et al. Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nature biotechnology. 2009;27(9):839-49.

Zhou J, Li H, Li S, Zaia J, Rossi JJ. Novel dual inhibitory function aptamer-siRNA delivery system for HIV-1 therapy. Molecular therapy : the journal of the American Society of Gene Therapy. 2008;16(8):1481-9.

McNamara JO, 2nd, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E, et al. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nature biotechnology. 2006;24(8):1005-15.

Chu TC, Twu KY, Ellington AD, Levy M. Aptamer mediated siRNA delivery. Nucleic acids research. 2006;34(10):e73.

Toloue MM, Ford LP. Antibody targeted siRNA delivery. Methods in molecular biology (Clifton, NJ). 2011;764:123-39.

Song E, Zhu P, Lee SK, Chowdhury D, Kussman S, Dykxhoorn DM, et al. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nature biotechnology. 2005;23(6):709-17.

Hayashi Y, Mori Y, Higashi T, Motoyama K, Jono H, Sah DW, et al. Systemic delivery of transthyretin siRNA mediated by lactosylated dendrimer/alpha-cyclodextrin conjugates into hepatocyte for familial amyloidotic polyneuropathy therapy. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2012;19 Suppl 1:47-9.

Patil S, Lalani R, Bhatt P, Vhora I, Patel V, Patel H, et al. Hydroxyethyl substituted linear polyethylenimine for safe and efficient delivery of siRNA therapeutics. RSC Advances. 2018;8(62):35461-73.

Thomas M, Klibanov AM. Enhancing polyethylenimine's delivery of plasmid DNA into mammalian cells. Proceedings of the National Academy of Sciences of the United States of America. 2002;99(23):14640-5.

Thomas M, Lu JJ, Ge Q, Zhang C, Chen J, Klibanov AM. Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(16):5679-84.

Thomas M, Ge Q, Lu JJ, Chen J, Klibanov AM. Cross-linked small polyethylenimines: while still nontoxic, deliver DNA efficiently to mammalian cells in vitro and in vivo. Pharmaceutical research. 2005;22(3):373-80.

Hunter AC. Molecular hurdles in polyfectin design and mechanistic background to polycation induced cytotoxicity. Advanced drug delivery reviews. 2006;58(14):1523-31.

Li Y, Wang J, Lee CGL, Wang CY, Gao SJ, Tang GP, et al. CNS gene transfer mediated by a novel controlled release system based on DNA complexes of degradable polycation PPE-EA: a comparison with polyethylenimine//DNA complexes. Gene therapy. 2004;11(1):109-14.

Patil S, Bhatt P, Lalani R, Amrutiya J, Vhora I, Kolte A, et al. Low molecular weight chitosan–protamine conjugate for siRNA delivery with enhanced stability and transfection efficiency. RSC Advances. 2016;6(112):110951-63.

Miyata K, Oba M, Nakanishi M, Fukushima S, Yamasaki Y, Koyama H, et al. Polyplexes from poly(aspartamide) bearing 1,2-diaminoethane side chains induce pH-selective, endosomal membrane destabilization with amplified transfection and negligible cytotoxicity. Journal of the American Chemical Society. 2008;130(48):16287-94.

Singha K, Namgung R, Kim WJ. Polymers in Small-Interfering RNA Delivery. Nucleic Acid Ther. 2011;21(3):133-47.

Kim HJ, Ishii A, Miyata K, Lee Y, Wu S, Oba M, et al. Introduction of stearoyl moieties into a biocompatible cationic polyaspartamide derivative, PAsp(DET), with endosomal escaping function for enhanced siRNA-mediated gene knockdown. Journal of controlled release : official journal of the Controlled Release Society. 2010;145(2):141-8.

Bhatt P, Lalani R, Vhora I, Patil S, Amrutiya J, Misra A, et al. Liposomes encapsulating native and cyclodextrin enclosed paclitaxel: Enhanced loading efficiency and its pharmacokinetic evaluation. Int J Pharm. 2018;536(1):95-107.

Bhatt P, Vhora I, Patil S, Amrutiya J, Bhattacharya C, Misra A, et al. Role of antibodies in diagnosis and treatment of ovarian cancer: Basic approach and clinical status. Journal of Controlled Release. 2016;226:148-67.

Bartlett DW, Davis ME. Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging. Nucleic acids research. 2006;34(1):322-33.

Kakutani K, Nishida K, Uno K, Takada T, Shimomura T, Maeno K, et al. Prolonged down regulation of specific gene expression in nucleus pulposus cell mediated by RNA interference in vitro. Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2006;24(6):1271-8.

Omi K, Tokunaga K, Hohjoh H. Long-lasting RNAi activity in mammalian neurons. FEBS letters. 2004;558(1-3):89-95.

Maliyekkel A, Davis BM, Roninson IB. Cell cycle arrest drastically extends the duration of gene silencing after transient expression of short hairpin RNA. Cell cycle (Georgetown, Tex). 2006;5(20):2390-5.

Zimmermann TS, Lee ACH, Akinc A, Bramlage B, Bumcrot D, Fedoruk MN, et al. RNAi-mediated gene silencing in non-human primates. Nature. 2006;441(7089):111-4.

Takabatake Y, Isaka Y, Mizui M, Kawachi H, Takahara S, Imai E. Chemically modified siRNA prolonged RNA interference in renal disease. Biochemical and biophysical research communications. 2007;363(2):432-7.

McLean JW, Fox EA, Baluk P, Bolton PB, Haskell A, Pearlman R, et al. Organ-specific endothelial cell uptake of cationic liposome-DNA complexes in mice. The American journal of physiology. 1997;273(1 Pt 2):H387-404.

Senior JH, Trimble KR, Maskiewicz R. Interaction of positively-charged liposomes with blood: implications for their application in vivo. Biochimica et biophysica acta. 1991;1070(1):173-9.

Tousignant JD, Gates AL, Ingram LA, Johnson CL, Nietupski JB, Cheng SH, et al. Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid:plasmid DNA complexes in mice. Human gene therapy. 2000;11(18):2493-513.

Filion MC, Phillips NC. Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells. Biochimica et biophysica acta. 1997;1329(2):345-56.

Tousignant JD, Zhao H, Yew NS, Cheng SH, Eastman SJ, Scheule RK. DNA sequences in cationic lipid:pDNA-mediated systemic toxicities. Human gene therapy. 2003;14(3):203-14.

Litzinger DC, Huang L. Phosphatodylethanolamine liposomes: drug delivery, gene transfer and immunodiagnostic applications. Biochim Biophys Acta - Reviews on Biomembranes. 1992;1113(2):201-27.

van der Woude I, Visser HW, ter Beest MB, Wagenaar A, Ruiters MH, Engberts JB, et al. Parameters influencing the introduction of plasmid DNA into cells by the use of synthetic amphiphiles as a carrier system. Biochimica et biophysica acta. 1995;1240(1):34-40.

Khatri N, Baradia D, Vhora I, Rathi M, Misra A. Development and Characterization of siRNA Lipoplexes: Effect of Different Lipids, In Vitro Evaluation in Cancerous Cell Lines and In Vivo Toxicity Study. AAPS PharmSciTech. 2014;15(6):1630-43.

Bhattacharya S, Haldar S. The effects of cholesterol inclusion on the vesicular membranes of cationic lipids. Biochim Biophys Acta - Biomembranes. 1996;1283(1):21-30.

Bhattacharya S, Haldar S. Interactions between cholesterol and lipids in bilayer membranes. Role of lipid headgroup and hydrocarbon chain-backbone linkage. Biochimica et biophysica acta. 2000;1467(1):39-53.

Bouxsein NF, McAllister CS, Ewert KK, Samuel CE, Safinya CR. Structure and gene silencing activities of monovalent and pentavalent cationic lipid vectors complexed with siRNA. Biochemistry. 2007;46(16):4785-92.

Radler JO, Koltover I, Salditt T, Safinya CR. Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science (New York, NY). 1997;275(5301):810-4.

Bouxsein NF, Ewert KK, McAllister CS, Evans HM, Samuel CE, Safinya CR. 184. Novel Cationic Multivalent Lipids Show Improved Delivery of siRNA and DNA. Molecular therapy : the journal of the American Society of Gene Therapy. 2006;13(S1):S71-S.

Aberle AM, Tablin F, Zhu J, Walker NJ, Gruenert DC, Nantz MH. A novel tetraester construct that reduces cationic lipid-associated cytotoxicity. Implications for the onset of cytotoxicity. Biochemistry. 1998;37(18):6533-40.

Bottega R, Epand RM. Inhibition of protein kinase C by cationic amphiphiles. Biochemistry. 1992;31(37):9025-30.

Omidi Y, Hollins AJ, Benboubetra M, Drayton R, Benter IF, Akhtar S. Toxicogenomics of non-viral vectors for gene therapy: a microarray study of lipofectin- and oligofectamine-induced gene expression changes in human epithelial cells. Journal of drug targeting. 2003;11(6):311-23.

Kongkaneramit L, Sarisuta N, Azad N, Lu Y, Iyer AK, Wang L, et al. Dependence of reactive oxygen species and FLICE inhibitory protein on lipofectamine-induced apoptosis in human lung epithelial cells. The Journal of pharmacology and experimental therapeutics. 2008;325(3):969-77.

Vhora I, Lalani R, Bhatt P, Patil S, Misra A. Lipid-nucleic acid nanoparticles of novel ionizable lipids for systemic BMP-9 gene delivery to bone-marrow mesenchymal stem cells for osteoinduction. International Journal of Pharmaceutics. 2019;563:324-36.

Vhora I, Lalani R, Bhatt P, Patil S, Patel H, Patel V, et al. Colloidally Stable Small Unilamellar Stearyl Amine Lipoplexes for Effective BMP-9 Gene Delivery to Stem Cells for Osteogenic Differentiation. 2018.

Aramaki Y, Takano S, Arima H, Tsuchiya S. Induction of Apoptosis in WEHI 231 Cells by Cationic Liposomes. Pharmaceutical research. 2000;17(5):515-20.

Aramaki Y, Takano S, Tsuchiya S. Induction of apoptosis in macrophages by cationic liposomes. FEBS letters. 1999;460(3):472-6.

Hickerson RP, Vlassov AV, Wang Q, Leake D, Ilves H, Gonzalez-Gonzalez E, et al. Stability Study of Unmodified siRNA and Relevance to Clinical Use. Oligonucleotides. 2008;18(4):345-54.

Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R, Donoghue M, et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature. 2004;432(7014):173-8.

Belting M, Petersson P. Intracellular Accumulation of Secreted Proteoglycans Inhibits Cationic Lipid-mediated Gene Transfer: CO-TRANSFER OF GLYCOSAMINOGLYCANS TO THE NUCLEUS. J Biol Chem. 1999;274(27):19375-82.

Labat-Moleur F, Steffan AM, Brisson C, Perron H, Feugeas O, Furstenberger P, et al. An electron microscopy study into the mechanism of gene transfer with lipopolyamines. Gene therapy. 1996;3(11):1010-7.

Behr JP, Demeneix B, Loeffler JP, Perez-Mutul J. Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA. Proceedings of the National Academy of Sciences of the United States of America. 1989;86(18):6982-6.

Plank C, Mechtler K, Szoka FC, Jr., Wagner E. Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery. Human gene therapy. 1996;7(12):1437-46.

Vitiello L, Bockhold K, Joshi PB, Worton RG. Transfection of cultured myoblasts in high serum concentration with DODAC:DOPE liposomes. Gene therapy. 1998;5(10):1306-13.

Ross PC, Hui SW. Lipoplex size is a major determinant of in vitro lipofection efficiency. Gene therapy. 1999;6(4):651-9.

Li S, Rizzo MA, Bhattacharya S, Huang L. Characterization of cationic lipid-protamine-DNA (LPD) complexes for intravenous gene delivery. Gene therapy. 1998;5(7):930-7.

Tros de Ilarduya C, Düzgüne? N. Efficient gene transfer by transferrin lipoplexes in the presence of serum. Biochim Biophys Acta - Biomembranes. 2000;1463(2):333-42.

Kolate A, Baradia D, Patil S, Vhora I, Kore G, Misra A. PEG - a versatile conjugating ligand for drugs and drug delivery systems. Journal of controlled release : official journal of the Controlled Release Society. 2014;192:67-81.

Shahiwala A, Misra A. In-Vitro and In-Vivo Tools in Drug Delivery Research for Optimum Clinical Outcomes2018.

Alemán LM, Doench J, Sharp PA. Comparison of siRNA-induced off-target RNA and protein effects. RNA. 2007;13(3):385-95.

Jackson AL, Linsley PS. Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application. Nat Rev Drug Discov. 2010;9(1):57-67.

Oliveira S, Storm G, Schiffelers RM. Targeted Delivery of siRNA. J Biomed Biotechnol. 2006;2006:63675.

Bunuales M, Duzgunes N, Zalba S, Garrido MJ, de Ilarduya CT. Efficient gene delivery by EGF-lipoplexes in vitro and in vivo. Nanomedicine (London, England). 2011;6(1):89-98.

Khatri N, Rathi M, Baradia D, Misra A. cRGD Grafted siRNA Nano-constructs for Chemosensitization of Gemcitabine Hydrochloride in Lung Cancer Treatment. Pharmaceutical research. 2014.

Khatri N, Baradia D, Vhora I, Rathi M, Misra A. cRGD grafted liposomes containing inorganic nano-precipitate complexed siRNA for intracellular delivery in cancer cells. Journal of controlled release : official journal of the Controlled Release Society. 2014;182:45-57.

Cardoso A, Trabulo S, Moreira JN, Düzgüne? N, de Lima MCP. Chapter 14 Targeted Lipoplexes for siRNA Delivery. In: Nejat D, editor. Methods Enzymol. Volume 465: Academic Press; 2009. p. 267-87.

Patel J, Amrutiya J, Bhatt P, Javia A, Jain M, Misra A. Targeted delivery of monoclonal antibody conjugated docetaxel loaded PLGA nanoparticles into EGFR overexpressed lung tumour cells. Journal of microencapsulation. 2018;35(2):204-17.

Vhora I, Patil S, Bhatt P, Gandhi R, Baradia D, Misra A. Receptor-targeted drug delivery: current perspective and challenges. Ther Deliv. 2014;5(9):1007-24.

Published

2021-03-31
Statistics
16 Views | 34 Downloads
Citatons

How to Cite

Miteshkumar Malaviya, and Milankumar Shiroya. “Systemic Gene Delivery Using Lipid Envelope Systems and Its Potential in Overcoming Challenges”. International Journal of Pharmaceutics and Drug Analysis, vol. 9, no. 1, Mar. 2021, pp. 46-55, doi:10.47957/ijpda.v9i1.458.

Issue

Section

Review Articles
Share |