Avidin grafted dextran nanostructure enables a month-long intra-discal retention.
Animals
Avidin
/ administration & dosage
Cattle
Dextrans
/ administration & dosage
Drug Delivery Systems
/ methods
Glycosaminoglycans
Half-Life
Injections
Intervertebral Disc
/ drug effects
Intervertebral Disc Degeneration
/ drug therapy
Low Back Pain
/ drug therapy
Nanostructures
/ administration & dosage
Nucleus Pulposus
/ drug effects
Static Electricity
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 07 2020
21 07 2020
Historique:
received:
24
02
2020
accepted:
17
06
2020
entrez:
23
7
2020
pubmed:
23
7
2020
medline:
22
12
2020
Statut:
epublish
Résumé
Low back pain is often the direct result of degeneration of the intervertebral disc. A wide range of therapeutics including anti-catabolic, pro-anabolic factors and chemo-attractants that can stimulate resident cells and recruit endogenous progenitors are under consideration. The avascular nature and the dense matrix of this tissue make it challenging for systemically administered drugs to reach their target cells inside the nucleus pulposus (NP), the central gelatinous region of the intervertebral disc (IVD). Therefore, local intra-discal injection of therapeutic drugs directly into the NP is a clinically relevant delivery approach, however, suffers from rapid and wide diffusion outside the injection site resulting in short lived benefits while causing systemic toxicity. NP has a high negative fixed charge density due to the presence of negatively charged aggrecan glycosaminoglycans that provide swelling pressures, compressive stiffness and hydration to the tissue. This negative fixed charge density can also be used for enhancing intra-NP residence time of therapeutic drugs. Here we design positively charged Avidin grafted branched Dextran nanostructures that utilize long-range binding effects of electrostatic interactions to bind with the intra-NP negatively charged groups. The binding is strong enough to enable a month-long retention of cationic nanostructures within the NP following intra-discal administration, yet weak and reversible to allow movement to reach cells dispersed throughout the tissue. The branched carrier has multiple sites for drug conjugation and can reduce the need for multiple injections of high drug doses and minimize associated side-effects, paving the way for effective clinical translation of potential therapeutics for treatment of low back pain and disc degeneration.
Identifiants
pubmed: 32694557
doi: 10.1038/s41598-020-68351-1
pii: 10.1038/s41598-020-68351-1
pmc: PMC7374582
doi:
Substances chimiques
Dextrans
0
Glycosaminoglycans
0
Avidin
1405-69-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
12017Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR069668
Pays : United States
Organisme : NIH HHS
ID : R01AR069668
Pays : United States
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