Innovations in Breaking Barriers: Liposomes as Near-Perfect Drug Carriers in Ischemic Stroke Therapy

Abstract

Liposomes, noted for their tunable particle size, surface customization, and varied drug delivery capacities, are increasingly acknowledged in therapeutic applications. These vesicles exhibit surface flexibility, enabling the incorporation of targeting moieties or peptides to achieve specific targeting and avoid lysosomal entrapment. Internally, their adaptable architecture permits the inclusion of a broad spectrum of drugs, contingent on their solubility characteristics. This study thoroughly reviews liposome fabrication, surface modifications, and drug release mechanisms post-systemic administration, with a particular emphasis on drugs crossing the blood-brain barrier (BBB) to address lesions. Additionally, the review delves into recent developments in the use of liposomes in ischemic stroke models, offering a comparative evaluation with other nanocarriers like exosomes and nano-micelles, thereby facilitating their clinical advancement.

Graphical Abstract

Keywords:

• liposome
• BBB
• ischemic stroke
• drug carrier
• liposome-based engineering

Abbreviations

ABC, Accelerated blood clearance; AEPO, Asialo-erythropoietin; AMPA, Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ATP, Adenosine Triphosphate; BBB, Blood-brain barrier; Bcl-2, B-cell lymphoma-2; BECs, Brain endothelial cells; bFGF, Basic Fibroblast Growth Factor; CDPC, Cytidine-5’-diphosphocholine; CREKA, Cysteinyl-arginyl-glutamyl-lysyl-alanyl; CsPLTs, Cryo-shocked platelets; DC-Cholesterol, 3-[N-(N’,N’-dimethylaminoethane)-carbamoyl]cholesterol hydrochloride; DHA, Docosahexaenoic acid; DSPE, Dioleoyl phosphatidylethanolamine; DSPE-PEG, 1.2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; EPO, Erythropoietin; FBP, Fibrin-binding peptide; GB, Ginkinolide B; GM1, Monosialoganglioside; Hb, Hemoglobin; HT, Hemorrhagic transformation; HYD, Hydroxyurea; I/R, Ischemia/reperfusion; ICH, Intracerebral hemorrhage; IL-1, Interleukin-1; IL-5, Interleukin-5; IONPs, Iron Oxide Nanoparticles; LCST, Lower critical solution temperature; mtDNA, Mitochondrial DNA; mtROS, Mitochondrial reactive oxygen species; M / Ns, Monocytes and neutrophils; MCAO, Middle cerebral artery occlusion; MMP, Matrix metalloproteinase; MMP-2, Matrix Metalloproteinase 2; MMPs, Matrix metalloproteinases; NADH, Nicotinamide adenine dinucleotide; NMDA, N-methyl-D-aspartate; NMDARs, N-methyl-D-aspartate receptors; NOX, Nicotinamide adenine dinucleotide phosphate oxidase; NLRP1, NLR family pyrin-domain-containing protein 1; NLR, NLRP3 family pyrin-domain-containing protein 3; Nrf2, Nuclear Factor E2-Related Factor 2; OGD, Oxygen glucose deprivation; P2X4, Purinergic Receptor P2X, Ligand-Gated Ion Channel, 4; PBP, Platelet-binding peptide; p-DBSN, Dodecylbenzene sulfonamide; PDTC, Pyrrolidine dithiocarbamate; PEG, Polyethylene glycol; PEG-Lip, PEGylated liposomes; PEG-PNIPAM, Polyethylene glycol-poly(N-isopropylacrylamide); pH, Potential of hydrogen; PirB, Paired immunoglobulin-like receptor B; PPC, Peptide/cholesterol; PS, Phosphatidylserine; ROS, Reactive oxygen species; SHp, Strokehoming peptide; sPirB, Soluble Paired immunoglobulin-like receptor B; TF, Transferrin; TGF-β, Transforming Growth Factor beta; TJ, Tight junction; TNF-α, Tumor Necrosis Factor-alpha; tPA, Tissue plasminogen activator; VCAM-1, Vascular Cell Adhesion Molecule-1; VLA-4, Very Late Antigen-4; 5BDBD, 5-(3-Bromophenyl)-1,3-dihydro-2H-Benzofuro[3,2-e]-1,4-diazepin-2-one.

Acknowledgment

We thank Fig.Draw (https://www.figdraw.com/) for editing Figures 2 and 6. Graphical abstract, Figures 1, 3, 4 and 5 were created with Biorender.com. We thank Dr. Yifan Bao for helping us obtain the copyright for the images drawn on the Biorender.com. Also we thank Dr. Ahmed Waqas for professional language polishing.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

This work was funded by the National Key R&D Program of China (2022YFA1104900 & 2022YFA1104904), the Innovation Team Project (2023KCXTD007) and the Special project in key areas of Guangdong Province (2021ZDZX2011), and the President Foundation of the Integrated Hospital of Traditional Chinese Medicine of Southern Medical University (1202101003).