Liposomal drug delivery in an in vitro 3D bone marrow model for multiple myeloma

Liposomal drug delivery in an in vitro 3D bone marrow model for multiple myeloma

Liposomal drug delivery can improve the therapeutic index of treatments for multiple myeloma. However, an appropriate 3D model for the in vitro evaluation of liposomal drug delivery is lacking. In this study, we applied a previously developed 3D bone marrow (BM) myeloma model to examine liposomal dr...

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Bibliographic Details
Published in:International journal of nanomedicine Vol. 13; pp. 8105 - 8118
Main Authors: Braham, Maaike Vj, Deshantri, Anil K, Minnema, Monique C, Öner, F Cumhur, Schiffelers, Raymond M, Fens, Marcel Ham, Alblas, Jacqueline
Format: Journal Article
Language:English
Published: New Zealand Dove Medical Press Limited 01-01-2018
Taylor & Francis Ltd
Dove Medical Press
Subjects:
Analysis
Anthracyclines
Antibiotics, Antineoplastic - administration & dosage
Antigens
Bone marrow
Bone Marrow - drug effects
Bone Marrow - pathology
Bortezomib
Cancer
Cancer therapies
Cell culture
Cell Proliferation
Chemotherapy
Doxorubicin - administration & dosage
drug delivery
Drug Delivery Systems
Drug resistance
drug sensitivity and resistance testing
Drug therapy
Drugs
Endothelium
Extracellular matrix
Health aspects
Humans
In Vitro Techniques
Integrins
Lipids
liposomes
Liposomes - administration & dosage
Medical research
Models, Biological
Multiple myeloma
Multiple Myeloma - drug therapy
Multiple Myeloma - pathology
Nanoparticles
Original Research
Patients
Peptides
Polyethylene glycol
Pore size
Stem cells
Tumor Cells, Cultured
tumor microenvironment
Tumors
Netherlands
targeted delivery
multiple myeloma
tumor microenvironment
liposomes
drug sensitivity and resistance testing
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Summary:Liposomal drug delivery can improve the therapeutic index of treatments for multiple myeloma. However, an appropriate 3D model for the in vitro evaluation of liposomal drug delivery is lacking. In this study, we applied a previously developed 3D bone marrow (BM) myeloma model to examine liposomal drug therapy. Liposomes of different sizes (~75-200 nm) were tested in a 3D BM myeloma model, based on multipotent mesenchymal stromal cells, endothelial progenitor cells, and myeloma cells cocultured in hydrogel. The behavior and efficacy of liposomal drug therapy was investigated, evaluating the feasibility of testing liposomal drug delivery in 3D in vitro. Intracellular uptake of untargeted and integrin α β (very late antigen-4) targeted liposomes was compared in myeloma and supporting cells, as well as the effectivity of free and liposome-encapsulated chemotherapy (bortezomib, doxorubicin). Either cocultured myeloma cell lines or primary CD138 myeloma cells received the treatments. Liposomes (~75-110 nm) passively diffused throughout the heterogeneously porous (~80-850 nm) 3D hydrogel model after insertion. Cellular uptake of liposomes was observed and was increased by targeting very late antigen-4. Liposomal bortezomib and doxorubicin showed increased cytotoxic effects toward myeloma cells compared with the free drugs, using either a cell line or primary myeloma cells. Cytotoxicity toward supporting BM cells was reduced using liposomes. The 3D model allows the study of liposome-encapsulated molecules on multiple myeloma and supporting BM cells, looking at cellular targeting, and general efficacy of the given therapy. The advantages of liposomal drug delivery were demonstrated in a primary myeloma model, enabling the study of patient-to-patient responses to potential drugs and treatment regimes.
ISSN:1178-2013
1176-9114
1178-2013
DOI:10.2147/IJN.S184262