Homing of liposomes to target cells

doi:10.1016/S0006-291X(75)80180-X

Biochemical and Biophysical Research Communications

Volume 65, Issue 2, 22 July 1975, Pages 537-544

https://doi.org/10.1016/S0006-291X(75)80180-X Get rights and content

Summary

The possibility of homing liposomes to target cells was investigated. Liposomes containing an antitumour drug and associated with molecular probes which exhibit a specific affinity for the surface of a variety of normal and malignant cells were prepared. In vitro and in vivo experiments suggested that such probes were capable of mediating selective cellular uptake of the associated liposomes and the entrapped drug. It is anticipated that liposomes designed to home may become important tools in the control of cell behaviour.

References (23)

GregoriadisG. et al.
FEBS Lett.
(1974)
JulianoR.L. et al.
Biochem. Biophys. Res. Comm.
(1975)
GregoriadisG.
FEBS Lett.
(1973)
GregoriadisG. et al.
Lancet
(1974)
MorellA.G. et al.
J. biol. Chem.
(1971)
RamsdenD.B. et al.
Journal of Chromatography
(1973)
LowryO.H. et al.
J. Biol. Chem.
(1951)
WarrenL.
J. biol. Chem.
(1959)
EylarE.H. et al.
GregoriadisG. et al.
J. Biol. Chem.
(1970)

KimelbergH.K. et al.

Biochim. Biophys. Acta

(1971)

Cited by (234)

Liposome-based delivery of biological drugs
2022, Chinese Chemical Letters
Citation Excerpt :
The ILs concept was developed as a way to synergize the actions of antibodies and liposomes. Gregoriadis et al. [107] first investigated the utilization of IgGs produced against different cells and found that they could selectively ingest liposomes. Leserman et al. [108] showed that antibodies coupled to the surface of liposomes resulted in particular contact with target cells.
Biological drugs are attracting tremendous attention in disease treatment. However, their application is significantly limited by their inherent properties, such as high hydrophilicity, poor membrane-permeability, low stability, and larger size. Liposome-based drug delivery systems are emerging as promising tools to improve their delivery, owing to their ability to reduce toxicity, improve bioavailability, and enhance the therapeutic efficacy of the drug by optimizing delivery to the specific target site. Here, we reviewed the types of liposomes and their applications as carriers for biological drugs to treat various diseases, emphasized the commercial products, and ultimately provided perspectives in this field.
Drug delivery systems for rheumatoid arthritis treatment
2022, Photophysics and Nanophysics in Therapeutics
Rheumatoid arthritis (RA), once considered a benign and nonprogressive disease, is a debilitating condition with serious physical, emotional, and economic consequences. Worldwide, the annual incidence of RA is approximately three cases per 10,000 populations, and the prevalence rate is approximately 1%. The incidence of RA increases with age and can be seen high between the ages of 35 and 50 years. NSAIDs, steroids and disease modifying anti rheumatic drugs (DMARD) are mainstay of therapy. Due to chronic nature of treatment it is needed to improve the drug delivery using different carriers. The special pathophysiological conditions prevailing in inflamed synovium can be utilized to target the drug. The identification of inflammatory mediators and specific targeting of DMARDs to reduce their secretion has great role in halting the progression of disease and improving quality of life. Various target receptors have been identified, the use novel nanocarriers such as liposomes, nanoparticles, dendrimers has been effectively done and reported. Selective expression of various receptors such as folate, CD 44 in such inflammatory conditions is used to effectively target these carriers. Finally effective use of monoclonal antibodies to target NFKB, beta cells, and IL has given a boost to treatment of RA.
Drug Delivery Systems
2020, Biomaterials Science: An Introduction to Materials in Medicine
Over the past 60 years of development, biomaterials have demonstrated outstanding versatility to ensure controlled, reproducible drug delivery. These drug delivery systems (DDS) have enhanced and/or enabled superior delivery for both traditional small molecule drugs and new classes of drugs, such as nucleic acids and proteins, which suffer from delivery challenges associated with instability and poor tissue localization. This chapter overviews DDS development, first by delving into historical perspectives and motivations for the continuous evolution of DDS from macro- to nano-scale followed by summaries of various drug delivery routes and challenges, design and formulation concepts, and regulatory considerations. Finally, notable developments in DDS-mediated disease treatments to date are detailed, and perspectives for future opportunities driven by innovations in biomaterials development are offered.
When liposomes met antibodies: Drug delivery and beyond
2020, Advanced Drug Delivery Reviews
Citation Excerpt :
The immunoliposome (IL) idea was proposed to combine the functions of antibodies and liposomes for synergistic effects. Gregoriadis et al. first explored the use of IgGs raised against different cells and observed selective liposome uptake [24]. Leserman et al. demonstrated that antibodies coupling on liposome surface led to specific interaction with target cells [25].
Drug encapsulated liposomes and monoclonal antibodies (Mabs) are two distinctively different classes of therapeutics, but both aim to become the ultimate “magic bullet”. While PEGylated liposomes rely on the enhanced permeability and retention (EPR) effect for accumulation in solid tumor tissues, Mabs are designed to bind tightly to specific surface antigens on target cells to exert effector functions. Immunoliposome (IL) refers to the structural combination of liposomes and antibodies, whereas the antibodies are usually decorated on the liposome surface. ILs can therefore take advantage of interactions between antibodies and cancer cells for more efficient endocytosis and intracellular drug delivery. The antibody structure, affinity, density, as well as the liposome surface properties and drug to lipid ratios all contribute to the IL pharmacokinetic(PK) and pharmacodynamic(PD) behaviors. The optimal formulation parameters may vary for different target cells and tissues. Furthermore, besides the delivery of cytotoxic drugs to cancer cells, new ILs are being developed to interact with multiple target receptors, multiple target cells and trigger multiple therapeutic effects. We envision that the IL format can be a great platform for the molecular engineering of multi-valent, multi-specific interactions to achieve complex biological functions for therapeutic benefits, especially in the area of cancer immunotherapy.
Sortaggable liposomes: Evaluation of reaction conditions for single-domain antibody conjugation by Sortase-A and targeting of CD11b <sup>+</sup> myeloid cells
2018, European Journal of Pharmaceutics and Biopharmaceutics
Citation Excerpt :
The conjugation reaction between labile ligands and liposomes should be feasible under mild conditions in aqueous environment, it should conjugate expensive proteins with high yields and deliver homogenous reaction products that are reliably anchored in the bilayer. First attempts attached targeting motifs in an adsorptive fashion [5,6], followed by covalent IgG coupling with unspecific amine-cross linkers [7], disulfide [8] and thiol-maleimide chemistry [9] or more sophisticated methods, as reviewed by Marques-Gallego et al. [4]. Although conjugation methods evolved towards regio-specific reactions [10], these strategies are still not routinely used for ligand attachment in current scientific reports.
Active targeting with ligand coated liposomal drug delivery systems is a means to increase the therapeutic index of drugs. Stable ligand coating requires bilayer anchorage of the commonly proteinaceous ligands and hence a conjugation of lipid structures towards amino acids. This often leads to heterogeneous reaction products especially when chemical coupling methods are employed. Chemoenzymatic Sortase-A mediated transpeptidation (sortagging) is a useful tool to avoid this protein heterogeneity through its site-specific, bioorthogonal ligation mechanism. Manufacturing of such sortaggable, pentaglycine modified liposomes was developed by adaption of a scalable solvent injection technique. The pentaglycine liposomes were prepared with different degrees of PEGylation and steric accessibility of the pentaglycine motif. Comparable hydrodynamic diameters (146–188 nm) of the different formulations were obtained after a flow rate screening. The sortagging reactivity of a single-domain antibody (VHH) towards the pentaglycine liposomes was strongly dependent on the steric accessibility of the pentaglycine nucleophile. Adjusting the pentaglycine to ligand ratio improved conversion rates up to 80%. The liposome bound VHH was accessible for its soluble antigen as shown by a chromatography-based binding assay. Mono- and granulocytes could be selectively targeted in vitro by conjugation of BMX1, a VHH directed towards human myeloid cell surface marker CD11b. Confocal microscopy revealed intracellular localization of the targeted liposomes. The developability of those pentaglycine liposomes as well as their proof of principle for targeted drug delivery shows their potential for further investigation, for example as delivery platform for diagnostics or drugs into the tumor microenvironment.
Sandy Florence: The renaissance man
2016, International Journal of Pharmaceutics

View all citing articles on Scopus

View full text

Homing of liposomes to target cells

Summary

FEBS Lett.

Biochem. Biophys. Res. Comm.

FEBS Lett.

Lancet

J. biol. Chem.

Journal of Chromatography

J. Biol. Chem.

J. biol. Chem.

J. Biol. Chem.

Biochim. Biophys. Acta