Versatility of Liposomes for Antisense Oligonucleotide Delivery: A Special Focus on Various Therapeutic Areas

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2023 May 27

PMID 37242677

Authors

Raghav Gupta

Sagar Salave

Dhwani Rana

Bharathi Karunakaran

Arun Butreddy

Derajram Benival

Nagavendra Kommineni

Affiliations

Soon will be listed here.

Abstract

Nucleic acid therapeutics, specifically antisense oligonucleotides (ASOs), can effectively modulate gene expression and protein function, leading to long-lasting curative effects. The hydrophilic nature and large size of oligonucleotides present translational challenges, which have led to the exploration of various chemical modifications and delivery systems. The present review provides insights into the potential role of liposomes as a drug delivery system for ASOs. The potential benefits of liposomes as an ASO carrier, along with their method of preparation, characterization, routes of administration, and stability aspects, have been thoroughly discussed. A novel perspective in terms of therapeutic applications of liposomal ASO delivery in several diseases such as cancer, respiratory disease, ophthalmic delivery, infectious diseases, gastrointestinal disease, neuronal disorders, hematological malignancies, myotonic dystrophy, and neuronal disorders remains the major highlights of this review.

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References

Quemener A, Centomo M, Sax S, Panella R . Small Drugs, Huge Impact: The Extraordinary Impact of Antisense Oligonucleotides in Research and Drug Development. Molecules. 2022; 27(2). PMC: 8781596. DOI: 10.3390/molecules27020536. View

Salave S, Rana D, Benival D . Encapsulation of Anabolic Peptide in Lipid Nano Vesicles for Osteoporosis. Curr Protein Pept Sci. 2022; 23(7):495-503. DOI: 10.2174/1389203723666220822120305. View

Wang Y, Miao L, Satterlee A, Huang L . Delivery of oligonucleotides with lipid nanoparticles. Adv Drug Deliv Rev. 2015; 87:68-80. PMC: 4539950. DOI: 10.1016/j.addr.2015.02.007. View

Wan W, Seth P . The Medicinal Chemistry of Therapeutic Oligonucleotides. J Med Chem. 2016; 59(21):9645-9667. DOI: 10.1021/acs.jmedchem.6b00551. View

Yang J, Luo S, Zhang J, Yu T, Fu Z, Zheng Y . Exosome-mediated delivery of antisense oligonucleotides targeting α-synuclein ameliorates the pathology in a mouse model of Parkinson's disease. Neurobiol Dis. 2020; 148:105218. DOI: 10.1016/j.nbd.2020.105218. View

Yu R, Grundy J, Geary R . Clinical pharmacokinetics of second generation antisense oligonucleotides. Expert Opin Drug Metab Toxicol. 2012; 9(2):169-82. DOI: 10.1517/17425255.2013.737320. View

Lysik M, Wu-Pong S . Innovations in oligonucleotide drug delivery. J Pharm Sci. 2003; 92(8):1559-73. PMC: 7094321. DOI: 10.1002/jps.10399. View

Griffey R, Monia B, Cummins L, Freier S, Greig M, Guinosso C . 2'-O-aminopropyl ribonucleotides: a zwitterionic modification that enhances the exonuclease resistance and biological activity of antisense oligonucleotides. J Med Chem. 1996; 39(26):5100-9. DOI: 10.1021/jm950937o. View

Rinaldi C, Wood M . Antisense oligonucleotides: the next frontier for treatment of neurological disorders. Nat Rev Neurol. 2017; 14(1):9-21. DOI: 10.1038/nrneurol.2017.148. View

10.

Stein C, Mori K, Loke S, Subasinghe C, Shinozuka K, Cohen J . Phosphorothioate and normal oligodeoxyribonucleotides with 5'-linked acridine: characterization and preliminary kinetics of cellular uptake. Gene. 1988; 72(1-2):333-41. DOI: 10.1016/0378-1119(88)90160-6. View

11.

Yadava P, Gibbs M, Castro C, Hughes J . Effect of lyophilization and freeze-thawing on the stability of siRNA-liposome complexes. AAPS PharmSciTech. 2008; 9(2):335-41. PMC: 2976943. DOI: 10.1208/s12249-007-9000-1. View

12.

Salave S, Rana D, Benival D . Dual Targeting Anti-Osteoporotic Therapy through Potential Nanotherapeutic Approaches. Pharm Nanotechnol. 2022; . DOI: 10.2174/2211738510666220902124653. View

13.

Aoki M, Morishita R, Higaki J, Moriguchi A, Kida I, Hayashi S . In vivo transfer efficiency of antisense oligonucleotides into the myocardium using HVJ-liposome method. Biochem Biophys Res Commun. 1997; 231(3):540-5. DOI: 10.1006/bbrc.1996.5762. View

14.

Loke S, Stein C, Zhang X, Mori K, Nakanishi M, Subasinghe C . Characterization of oligonucleotide transport into living cells. Proc Natl Acad Sci U S A. 1989; 86(10):3474-8. PMC: 287160. DOI: 10.1073/pnas.86.10.3474. View

15.

Yu B, Mao Y, Bai L, Herman S, Wang X, Ramanunni A . Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia. Blood. 2012; 121(1):136-47. PMC: 3538326. DOI: 10.1182/blood-2012-01-407742. View

16.

Schlingensiepen K, Schlingensiepen R, Steinbrecher A, Hau P, Bogdahn U, Fischer-Blass B . Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009. Cytokine Growth Factor Rev. 2005; 17(1-2):129-39. DOI: 10.1016/j.cytogfr.2005.09.002. View

17.

Gales L . Tegsedi (Inotersen): An Antisense Oligonucleotide Approved for the Treatment of Adult Patients with Hereditary Transthyretin Amyloidosis. Pharmaceuticals (Basel). 2019; 12(2). PMC: 6631675. DOI: 10.3390/ph12020078. View

18.

Pakunlu R, Wang Y, Saad M, Khandare J, Starovoytov V, Minko T . In vitro and in vivo intracellular liposomal delivery of antisense oligonucleotides and anticancer drug. J Control Release. 2006; 114(2):153-62. DOI: 10.1016/j.jconrel.2006.06.010. View

19.

Saffari M, Moghimi H, Dass C . Barriers to Liposomal Gene Delivery: from Application Site to the Target. Iran J Pharm Res. 2017; 15(Suppl):3-17. PMC: 5242347. View

20.

Geary R, Norris D, Yu R, Bennett C . Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides. Adv Drug Deliv Rev. 2015; 87:46-51. DOI: 10.1016/j.addr.2015.01.008. View