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Cited by 1,334Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsDrug Solubulity and Delivery Systems

The DOI matches its Crossref record; 129 of the 131 references it cites were found in a registry or an index.

A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives

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Liu, Peng, Chen, Guiliang, Zhang, Jingchen·2022·Molecules
DOI 10.3390/molecules27041372PMC PMC8879473
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Abstract

Liposomes have been considered promising and versatile drug vesicles. Compared with traditional drug delivery systems, liposomes exhibit better properties, including site-targeting, sustained or controlled release, protection of drugs from degradation and clearance, superior therapeutic effects, and lower toxic side effects. Given these merits, several liposomal drug products have been successfully approved and used in clinics over the last couple of decades. In this review, the liposomal drug products approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) are discussed. Based on the published approval package in the FDA and European public assessment report (EPAR) in EMA, the critical chemistry information and mature pharmaceutical technologies applied in the marketed liposomal products, including the lipid excipient, manufacturing methods, nanosizing technique, drug loading methods, as well as critical quality attributions (CQAs) of products, are introduced. Additionally, the current regulatory guidance and future perspectives related to liposomal products are summarized. This knowledge can be used for research and development of the liposomal drug candidates under various pipelines, including the laboratory bench, pilot plant, and commercial manufacturing.

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Crossref · 10.3390/molecules27041372

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Figures

Figure 1 Categories and structures of liposomal drug delivery system. (a) Structural illustration of liposome composition. The size of a typical phospholipid bilayer is 4.5 nm, which is much smaller than the one of the inner aqueous core; (b) Classification of liposomal vesicles according to their lamellarity/compartment and particle size; (c) The size and lamellarity of different types of liposomes; (d,e) The cryo-transmission electron microscopy of Doxil [35] and Vyxeos [36]; (f,g) The electron micrographs of DepoFoamTM particles with a typical diameter of 1–100 μm (e.g., DepoCyt) and MLVs with a typical diameter of 0.2–5 μm (e.g., Mepact) [37].
Figure 1 Categories and structures of liposomal drug delivery system. (a) Structural illustration of liposome composition. The size of a typical phospholipid bilayer is 4.5 nm, which is much smaller than the one of the inner aqueous core; (b) Classification of liposomal vesicles according to their lamellarity/compartment and particle size; (c) The size and lamellarity of different types of liposomes; (d,e) The cryo-transmission electron microscopy of Doxil [35] and Vyxeos [36]; (f,g) The electron micrographs of DepoFoamTM particles with a typical diameter of 1–100 μm (e.g., DepoCyt) and MLVs with a typical diameter of 0.2–5 μm (e.g., Mepact) [37].CC BY · PubMed Central
Figure 2 (a) Structural illustration of glycerolphospholipid. R1 and R2 can be saturated or unsaturated fatty acids, such as decanoic acid, lauric acid, palmitic acid, oleic acid, myristic acid, stearic acid, and erucic acid. R3 can be phosphatidylcholine (PC), phosphatidyl ethanolamine (PE), phosphatidyl serine (PS), phosphatidyl inositols (PI), phosphatidic acid (PA), phosphatidylglycerol (PG), and cardiolipin; (b) Structure of sphingomyelin. (c) Structure of cholesterol.
Figure 2 (a) Structural illustration of glycerolphospholipid. R1 and R2 can be saturated or unsaturated fatty acids, such as decanoic acid, lauric acid, palmitic acid, oleic acid, myristic acid, stearic acid, and erucic acid. R3 can be phosphatidylcholine (PC), phosphatidyl ethanolamine (PE), phosphatidyl serine (PS), phosphatidyl inositols (PI), phosphatidic acid (PA), phosphatidylglycerol (PG), and cardiolipin; (b) Structure of sphingomyelin. (c) Structure of cholesterol.CC BY · PubMed Central
Figure 3 The potential manufacturing processes of the marketed liposomal products, summarized based on the related patents or publications.
Figure 3 The potential manufacturing processes of the marketed liposomal products, summarized based on the related patents or publications.CC BY · PubMed Central
Figure 4 Different mechanisms of remote drug loading. (a) Doxil: DOX-loaded by transmembrane gradient of (NH4)2SO4 concentration [35]; (b) Myocet, Marqibo, and DaunoXome: drug loaded by transmembrane gradient of pH; (c) Mepact: MDP chemically conjugated to PE through a peptide spacer, then formed liposomes with other phospholipids. (d) Onivyde: irinote can loaded by transmembrane gradient of the concentration of sucrosofate triethylammonium salt (TEA-SOS). One molecule of SOS can bind 8 molecules of irinotecan.
Figure 4 Different mechanisms of remote drug loading. (a) Doxil: DOX-loaded by transmembrane gradient of (NH4)2SO4 concentration [35]; (b) Myocet, Marqibo, and DaunoXome: drug loaded by transmembrane gradient of pH; (c) Mepact: MDP chemically conjugated to PE through a peptide spacer, then formed liposomes with other phospholipids. (d) Onivyde: irinote can loaded by transmembrane gradient of the concentration of sucrosofate triethylammonium salt (TEA-SOS). One molecule of SOS can bind 8 molecules of irinotecan.CC BY · PubMed Central
Figure 5 The phase transition of liposomal bilayer dispersed in aqueous solution. Heating above the melting temperature (Tm), the phase of bilayer transits from “solid” gel phase (Lβ: hexagonal lattice untitled chain or Lβ’: quasi hexagonal array with titled chain) (ordered state) to liquid crystalline phase (Lα) (disordered state). Cooling below Tc, the phase of bilayer transits from “solid” gel phase (Lβ or Lβ’) (ordered state) to subgel phase or crystalline phase (Lc) (ordered state).
Figure 5 The phase transition of liposomal bilayer dispersed in aqueous solution. Heating above the melting temperature (Tm), the phase of bilayer transits from “solid” gel phase (Lβ: hexagonal lattice untitled chain or Lβ’: quasi hexagonal array with titled chain) (ordered state) to liquid crystalline phase (Lα) (disordered state). Cooling below Tc, the phase of bilayer transits from “solid” gel phase (Lβ or Lβ’) (ordered state) to subgel phase or crystalline phase (Lc) (ordered state).CC BY · PubMed Central
Figure 6 The comparison profiles of publications using setting TITLE-ABS-KEY as “liposome”, “(liposome AND medicine) or (liposome AND drug)”, “(nano AND liposomes AND medicine) or (nano AND liposomes AND drug) and “(nano AND medicine) or (nano AND drug)” in the year range between 1970 and 2020 in Scopus.
Figure 6 The comparison profiles of publications using setting TITLE-ABS-KEY as “liposome”, “(liposome AND medicine) or (liposome AND drug)”, “(nano AND liposomes AND medicine) or (nano AND liposomes AND drug) and “(nano AND medicine) or (nano AND drug)” in the year range between 1970 and 2020 in Scopus.CC BY · PubMed Central

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Research works printed but not linked: 1

  1. Sakamoto, K., Lochhead, R.Y., Maibach, H.I., and Yamashita, Y. (2017). Liposomes for Cosmetics. Cosmetic Science and Technology, Elsevier.

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Metadata

Authors
Liu, P., Chen, G., & Zhang, J.
Affiliations
Shanghai Center for Drug Evaluation and Inspection, Haiqu Road 58, Shanghai 201210, China
Corresponding author
  • Liu, Peng
  • Zhang, Jingchen
ORCID
Venue
Molecules
Publisher
MDPI AG
Published
2022-02-17
Volume
27
Issue
4
Pages
1372
ISSN
1420-3049 (ISSN-L)
DOI
10.3390/molecules27041372
PMC
PMC8879473
OpenAlex
W4212801432
Cited by
1,334
References
130
Citations by year
2026: 243 · 2025: 455 · 2024: 361 · 2023: 222 · 2022: 52
FWCI
18.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecules (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Keywords
liposomes, liposomal drug delivery, regulatory guidelines, lipid excipients, nanosizing, drug loading methods, critical quality attributes, pharmaceutical manufacturing, sustained drug release
MeSH terms
Consumer Product Safety, Drug and Narcotic Control, Drug Carriers, Europe, Humans, Liposomes, United States, United States Food and Drug Administration, Molecular Structure, Drug Delivery Systems, Drug Approval

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