Cationic peptide carriers enable long-term delivery of insulin-like growth factor-1 to suppress osteoarthritis-induced matrix degradation.
Arthritis Res Ther
; 24(1): 172, 2022 07 20.
Article
in En
| MEDLINE
| ID: mdl-35858920
ABSTRACT
BACKGROUND:
Insulin-like growth factor-1 (IGF-1) has the potential to be used for osteoarthritis (OA) treatment but has not been evaluated in clinics yet owing to toxicity concerns. It suffers from short intra-joint residence time and a lack of cartilage targeting following its intra-articular administration. Here, we synthesize an electrically charged cationic formulation of IGF-1 by using a short-length arginine-rich, hydrophilic cationic peptide carrier (CPC) with a net charge of +14, designed for rapid and high uptake and retention in both healthy and arthritic cartilage.METHODS:
IGF-1 was conjugated to CPC by using a site-specific sulfhydryl reaction via a bifunctional linker. Intra-cartilage depth of penetration and retention of CPC-IGF-1 was compared with the unmodified IGF-1. The therapeutic effectiveness of a single dose of CPC-IGF-1 was compared with free IGF-1 in an IL-1α-challenged cartilage explant culture post-traumatic OA model.RESULTS:
CPC-IGF-1 rapidly penetrated through the full thickness of cartilage creating a drug depot owing to electrostatic interactions with negatively charged aggrecan-glycosaminoglycans (GAGs). CPC-IGF-1 remained bound within the tissue while unmodified IGF-1 cleared out. Treatment with a single dose of CPC-IGF-1 effectively suppressed IL-1α-induced GAG loss and nitrite release and rescued cell metabolism and viability throughout the 16-day culture period, while free IGF at the equivalent dose was not effective.CONCLUSIONS:
CPC-mediated depot delivery of IGF-1 protected cartilage by suppressing cytokine-induced catabolism with only a single dose. CPC is a versatile cationic motif that can be used for intra-cartilage delivery of other similar-sized drugs.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoarthritis
/
Cartilage, Articular
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Arthritis Res Ther
Journal subject:
REUMATOLOGIA
Year:
2022
Type:
Article
Affiliation country:
United States