Advancing Medicine with Lipid-Based Nanosystems—The Successful Case of Liposomes
Abstract
:1. Introduction
1.1. A Brief History of Liposomes
1.2. Liposome Properties and Composition
1.3. Classification and Main Applications of Liposomes
2. Liposomes as Nanomedicine Tools
2.1. Liposomes for the Treatment of Fungal Infections
2.2. Liposomes for Cancer Management
2.3. Liposomes for the Delivery of Antibacterial Drugs
2.4. Liposomes for Ophthalmologic Applications
2.5. Liposomes in Analgesia
2.6. Liposomes in Vaccination
2.7. Liposomes for the Delivery of Immunosuppressive Drugs
2.8. Liposomes for Diagnostic Applications
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Classification of Liposomes | Composition and Main Properties |
---|---|
Conventional | Neutral or negatively charged phospholipids and/or cholesterol. |
Long circulating | Surface is coated with inert, biocompatible polymers; displays dose-independent, non-saturable, log-linear kinetics and increased bioavailability. |
pH−sensitive | Include phospholipids such as dioleoyl phosphatidyl ethanolamine (DOPE) with cholesteryl hemisuccinate (CHEMS) or oleic acid (OA); stable at neutral pH. |
Cationic | Composed of cationic lipids appropriate for loading negatively charged macromolecules, such as DNA, RNA, and oligonucleotides. |
Immunoliposomes | Conventional or long circulating liposomes with their surface coated with specific ligands (e.g., antibodies); can be recognized by receptors overexpressed at affected sites. |
Applications | General Features |
---|---|
Drug Delivery | Encapsulation of drugs for in vivo delivery, a major use of these lipid-based nanosystems. Liposomes delay drug clearance, change its biodistribution profile, and minimize potential toxic effects, ultimately enhancing the therapeutic index [36]. |
Vaccines | Liposomes can carry and deliver antigens to antigen-presenting cells, whilst protecting them from degradation. Liposomes that are injected intramuscularly or subcutaneously accumulate in the lymph nodes, which is advantageous for vaccines [11]. |
Gene Therapy | Liposomes can be used as carriers for DNA and nucleic acid-based therapeutics, including anti-sense oligonucleotides and siRNA [11,19,37]. |
Diagnostic | Probes can be encapsulated for imaging applications, such as magnetic resonance imaging [38] |
Supplements | Compounds such as glutathione and various vitamins have been associated to liposomes [39,40]. |
Cosmetics | Liposomes are being utilized to increase the topical delivery of main ingredients included in cosmetics [41]. |
Disease | Therapeutic Agent | Lipid Composition | Main Findings | Ref. | |
---|---|---|---|---|---|
Cancer | Lymphoma | L-asparaginase | EPC:Chol:GM1 EPC:Chol:PI EPC:Chol:SA | Liposomal formulations increased up to 15-fold the half-life of the enzyme in blood circulation, enhanced its antitumor effect, and improved survival rate, with no adverse events. | [30] |
Acylated L-asparaginase | EPC:Chol:PI EPC:Chol:SA | Liposomal formulations increased up to 8-fold the half-life of the enzyme in blood circulation and enhanced the antitumor effect, with no adverse events. | [50] | ||
Lewis lung carcinoma | L-asparaginase | SPC:Chol:DSPE-PEG | Liposomes loading L-asparaginase increased survival rate. | [31] | |
Melanoma | Hybrid molecule (L-tyrosine analogue conjugated with a triazene) | EPC:DSPE-PEG | Liposomes loaded with the hybrid molecule preferentially accumulated at tumor sites and significantly improved antimelanoma effect in subcutaneous and metastatic murine models devoid of toxicity. | [51] | |
Copper(II) complex | DMPC:Chol:DSPE-PEG DMPC:CHEMS:DSPE-PEG | Liposomal formulations greatly enhanced the antimelanoma activity of metal complex with no adverse events. | [52] | ||
Iron(III) complex | DOPE:DOPC:CHEMS:DSPE-PEG | Liposomes loading the metal complex displayed the highest antitumor activity, even when compared with the positive control, TMZ. No toxic effects were reported. | [53] | ||
Colon cancer | Copper(II) complex | DMPC:DOPE:CHEMS:DSPE-PEG | pH-sensitive liposomes loaded with copper(II) complex impaired tumor progression compared to the compound in the free form without toxic effects. | [54] | |
Zinc(II) complex | DOPE:DOPC:CHEMS:DSPE-PEG | pH-sensitive liposomes of zinc(II) complex reduced tumor progression in the same extent as the positive control 5-FU, using a 3-fold lower therapeutic dose and without toxic side effects. | [55] | ||
Inflammation | Rheumatoid arthritis | Superoxide dismutase | EPC:Chol:SA EPC:Chol:PI | Liposomal formulations improved the therapeutic activity of the enzyme. | [42] |
Superoxide dismutase (SOD) or acylated superoxide dismutase (Ac-SOD) | EPC:Chol:DSPE-PEG EPC:Chol:SA | DSPE-PEG liposomes loading SOD and Ac-SOD displayed the highest half-life times in blood circulation. All SOD and Ac-SOD liposomes accumulated at inflammation sites. DSPE-PEG liposomes loading Ac-SOD showed a faster anti-inflammatory effect. | [33] | ||
Infection | Mycobacterium avium | Paromomycin | DPPC:DPPG DMPC:DMPG:DSPE-PEG DPPC:DPPG:DSPE-PEG | Paromomycin-loaded liposomes significantly reduced bacterial loads in all infected organs, showing higher antimycobacterial activity than the positive control rifabutin. | [43] |
Rifabutin | PC:PS | RFB liposomal formulations reduced mycobacterial infection in a higher extent than the antibiotic in the free form both in therapeutic and prophylactic murine models. | [44] | ||
Mycobacterium tuberculosis | Rifabutin | DPPC:DPPG HPC:Chol:DSPE-PEG DPPC:PEG | DPPC:DPPG liposomes promoted a higher accumulation of RFB in liver, spleen and lung. This nanoformulation improved the antimycobacterial effect of RFB in the M. tuberculosis murine model. | [48] | |
Leishmania infantum | Paromomycin | DPPC:DPPG | Paromomycin-loaded liposomes displayed a superior reduction of parasite burden, even when compared with the commercial antileishmanial drug Glucantime®. | [43] | |
Ischemia-reperfusion | Superoxide dismutase | EPC:Chol:DSPE-PEG (SOD liposomes) EPC:Chol:DSPE-PEG:DSPE-PEG-maleimide (SOD enzymosomes) | SOD enzymosomes enhanced the therapeutic effect of the enzyme, compared to SOD liposomes. | [45] | |
Thromboembolism | Streptokinase | DSPC:Chol:DSPE-PEG | Liposomes loaded with streptokinase increased 16-fold the half-life of the protein in blood circulation. | [46] | |
Urokinase | DPPC:DSPE-PEG-NHS:DSPE-mPEG | Liposomal formulation improved the thrombolytic activity of urokinase, being safe. | [47] |
Clinical Application | Trade Name | Active Pharmaceutical Ingredient | Lipid Composition | Year of First Approval |
---|---|---|---|---|
Cancer | DaunoXome® | Daunorubicin | DSPC:Chol | 1996 |
DepoCyt® | Cytarabine | DOPC:DPPG:Chol:triolein | 1999 | |
Doxil®/Caelyx® | Doxorubicin | HSPC:Chol:DSPE-PEG2000 | 1995 | |
Myocet® | PC:Chol | 2001 | ||
Lipodox® | HSPC:Chol:DSPE-PEG2000 | 2012 | ||
Lipusu® | Paclitaxel | PC:Chol | 2006 | |
Mepact® | Mifamurtide | DOPS:POPC | 2009 | |
Marqibo® | Vincristine | Sphingomyelin:Chol | 2012 | |
Onivyde® | Irinotecan | DSPC:Chol:DSPE-PEG2000 | 2015 | |
Vyxeos® | Cytarabine and daunorubicin | DSPC:DSPG:Chol | 2017 | |
Fungal infections | AmBisome® | Amphotericin B | HSPC:Chol:DSPG | 1990 |
Amphocil® | Cholesteryl sulphate | 1993 | ||
Abelcet® | DMPC:DMPG | 1995 | ||
Amphotec® | Cholesteryl sulphate | 1996 | ||
Fungisome® | PC:Chol | 2003 | ||
Bacterial infections | Arikayce® | Amikacin | DPPC:Chol | 2018 |
Ocular disorders | Visudyne® | Verteporfin | DMPC:PG | 2000 |
Analgesia | DepoDur™ | Morphine sulfate | DOPC:DPPG:Chol:triolein | 2004 |
Exparel® | Bupivacaine | DEPC:DPPG:Chol:tricaprylin | 2011 | |
Vaccination | Epaxal® | Hepatitis A virus antigen, strain RGSB | DOPC:DOPE | 1993 |
Inflexal® V | Influenza virus antigen, strains A and B | DOPC:DOPE | 1997 | |
Mosquirix™ | RTS,S antigen | DOPC:Chol | 2015 | |
Shingrix | varicella zoster virus glycoprotein E | Chol:MPL:QS21 | 2017 | |
Comirnaty® | mRNA encoding for the SARS-CoV-2 spike protein | ALC-0315: ALC-015d:Chol:DSPC | 2020 | |
Spikevax™ | SM-102:PEG2000-DMG:Chol:DSPC | 2021 |
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Luiz, H.; Oliveira Pinho, J.; Gaspar, M.M. Advancing Medicine with Lipid-Based Nanosystems—The Successful Case of Liposomes. Biomedicines 2023, 11, 435. https://doi.org/10.3390/biomedicines11020435
Luiz H, Oliveira Pinho J, Gaspar MM. Advancing Medicine with Lipid-Based Nanosystems—The Successful Case of Liposomes. Biomedicines. 2023; 11(2):435. https://doi.org/10.3390/biomedicines11020435
Chicago/Turabian StyleLuiz, Hugo, Jacinta Oliveira Pinho, and Maria Manuela Gaspar. 2023. "Advancing Medicine with Lipid-Based Nanosystems—The Successful Case of Liposomes" Biomedicines 11, no. 2: 435. https://doi.org/10.3390/biomedicines11020435
APA StyleLuiz, H., Oliveira Pinho, J., & Gaspar, M. M. (2023). Advancing Medicine with Lipid-Based Nanosystems—The Successful Case of Liposomes. Biomedicines, 11(2), 435. https://doi.org/10.3390/biomedicines11020435