Focal drug administration via heparin-containing cryogel microcarriers reduces cancer growth and metastasis.
Animals
Antibiotics, Antineoplastic
/ administration & dosage
Breast Neoplasms
/ drug therapy
Cell Survival
/ drug effects
Cryogels
/ administration & dosage
Doxorubicin
/ administration & dosage
Drug Carriers
/ administration & dosage
Drug Liberation
Female
Heparin
/ administration & dosage
Humans
MCF-7 Cells
Mice
Mice, Inbred NOD
Mice, SCID
Molecular Dynamics Simulation
Neoplasm Metastasis
/ drug therapy
Static Electricity
Tumor Burden
/ drug effects
Xenograft Model Antitumor Assays
Alexa Fluor™ 647 CID: 102227060
Cancer
Dimethyl sulfoxide (DMSO) CID: 679
Doxorubicin
Doxorubicin, hydrochloride salt CID: 443939
Heparin
Local drug delivery system
N-Ethyl-N′-(3-dimethylaminopropyl)carbodiimide (EDC) CID: 15908
N-Hydroxysulfosuccinimide (NHS) sodium salt CID: 133909
Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (Synperonic® PEP105) SID: 24888568
Sodium heparin CID: 22833565
Sulfated microcarrier
Toluene (≥99.5%) CID: 1140
Journal
Carbohydrate polymers
ISSN: 1879-1344
Titre abrégé: Carbohydr Polym
Pays: England
ID NLM: 8307156
Informations de publication
Date de publication:
01 Oct 2020
01 Oct 2020
Historique:
received:
02
04
2020
revised:
11
05
2020
accepted:
21
05
2020
entrez:
29
7
2020
pubmed:
29
7
2020
medline:
7
4
2021
Statut:
ppublish
Résumé
Developing drug delivery systems that release anticancer drugs in a controlled and sustained manner remains challenging. We hypothesized that highly sulfated heparin-based microcarriers would allow electrostatic drug binding and controlled release. In silico modelling showed that the anticancer drug doxorubicin has affinity for the heparin component of the microcarriers. Experimental results showed that the strong electrostatic interaction was reversible, allowing both doxorubicin loading and a subsequent slow release over 42 days without an initial burst release. The drug-loaded microcarriers were able to reduce cancer cell viability in vitro in both hormone-dependent and highly aggressive triple-negative human breast cancer cells. Focal drug treatment, of an in vivo orthotopic triple-negative breast cancer model significantly decreased tumor burden and reduced cancer metastasis, whereas systemic administration of an equivalent drug dose was ineffective. This study proves that heparin-based microcarriers can be used as drug delivery platforms, for focal delivery and sustained long-term drug release.
Identifiants
pubmed: 32718615
pii: S0144-8617(20)30678-0
doi: 10.1016/j.carbpol.2020.116504
pii:
doi:
Substances chimiques
Antibiotics, Antineoplastic
0
Cryogels
0
Drug Carriers
0
Doxorubicin
80168379AG
Heparin
9005-49-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
116504Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.