A biocompatible reverse thermoresponsive polymer for ocular drug delivery

Autor: Elsa C. Chan, Joseph Paul, Sze Ng, Roshan T. A. Mayadunne, Steven Ngo, Asitha Indaka Balachandra, Peter van Wijngaarden, Vicki Chrysostomou
Rok vydání: 2020
Předmět:
Male
Intraocular pressure
Time Factors
genetic structures
Polymers
Pharmaceutical Science
Angiogenesis Inhibitors
02 engineering and technology
Pharmacology
030226 pharmacology & pharmacy
ocular drug delivery
chemistry.chemical_compound
0302 clinical medicine
Drug Delivery Systems
media_common
Aflibercept
Temperature
intravitreal injection
General Medicine
021001 nanoscience & nanotechnology
Vascular endothelial growth factor
Bevacizumab
Drug delivery
Intravitreal Injections
0210 nano-technology
medicine.drug
Research Article
Drug
macular degeneration
media_common.quotation_subject
Recombinant Fusion Proteins
Retina
Cell Line
03 medical and health sciences
In vivo
medicine
Animals
Humans
Rats
Long-Evans
anti-vascular endothelial growth factor
Intraocular Pressure
business.industry
lcsh:RM1-950
Macular degeneration
medicine.disease
eye diseases
Rats
Drug Liberation
Receptors
Vascular Endothelial Growth Factor
lcsh:Therapeutics. Pharmacology
chemistry
Delayed-Action Preparations
reverse thermoresponsive polymer
sense organs
business
Zdroj: Drug Delivery, Vol 26, Iss 1, Pp 343-353 (2019)
Drug Delivery
DOI: 10.6084/m9.figshare.7886093
Popis: Age-related macular degeneration (AMD) is a leading cause of vision loss, the treatment of which may require monthly intravitreal injections. This is a burden on patients and health services, and new delivery modalities that reduce injection frequency are required. To that end, we investigated the suitability of a novel reverse thermoresponsive polymer (RTP) as an ocular drug-delivery vehicle. In this work, we detail the structure and synthesis of a novel RTP, and determine drug release curves for two drugs commonly used in the treatment of AMD, bevacizumab and aflibercept. Biocompatibility of the RTP was assessed in vitro in human and rat cell lines and in vivo following intravitreal injection in rats. Bevacizumab demonstrated a more appropriate release profile than aflibercept, with 67% released within 14 days and 78% released in total over a 183-day period. No toxic effects of RTP were seen in human or rat cells in up to 14 days of co-culture with RTP. Following intravitreal injection, intraocular pressure was unaffected by the presence of RTP and no changes in retinal function or structure were observed at 1 week or 1 month post-injection. RTP injection did not cause inflammation, gliosis or apoptosis in the retina. This work demonstrates the potential suitability of the novel RTP as a sustained-release vehicle for ocular drug delivery for anti-neovascular therapies. Optimization of polymer chemistry for optimal drug loading and release is needed.
Databáze: OpenAIRE
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