Synthesis and Characterisation of Photocrosslinked poly(ethylene glycol) diacrylate Implants for Sustained Ocular Drug Delivery

• Published in: Pharmaceutical research Vol. 35; no. 2; pp. 36 - 17
• Main Authors: McAvoy, Kathryn, Jones, David, Thakur, Raghu Raj Singh
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2018; Springer; Springer Nature B.V
• Subjects: Adaptation; Administration, Ophthalmic; Albumin; Analytical methods; Biochemistry; Biocompatibility; Biological activity; Biological Products - administration & dosage; Biological Products - pharmacokinetics; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cell Line; Corticosteroids; Diabetic Retinopathy - drug therapy; Drug Compounding - methods; Drug delivery; Drug delivery systems; Drug Delivery Systems - methods; Drug Implants; Drug Liberation; Drugs; Enzyme-linked immunosorbent assay; Epithelial cells; Ethylene glycol; Fluocinolone; Fluocinolone acetonide; Glucocorticoids - administration & dosage; Glucocorticoids - pharmacokinetics; High-performance liquid chromatography; Humans; Liquid chromatography; Macular Degeneration - drug therapy; Materials Testing; Medical Law; Molecular Weight; Ophthalmic drugs; Ovalbumin; Ovalbumin - administration & dosage; Ovalbumin - pharmacokinetics; Pharmacology/Toxicology; Pharmacy; Polyethylene glycol; Polyethylene Glycols - chemical synthesis; Polymers; Pore formation; Porosity; Research Paper; Retina; Retinal Pigment Epithelium - cytology; Retinal Pigment Epithelium - drug effects; Systems analysis; Transplants & implants; Triamcinolone; Triamcinolone acetonide; Triamcinolone Acetonide - administration & dosage; Triamcinolone Acetonide - pharmacokinetics; Vehicles; ocular drug delivery; poly(ethylene glycol) diacrylate; triamcinolone acetonide; protein delivery; photocrosslinked
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-017-2298-9

Purpose To investigate the sustained ocular delivery of small and large drug molecules from photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) implants with varying pore forming agents. Methods Triamcinolone acetonide and ovalbumin loaded photocrosslinked PEGDA implants, with or without pore-forming agents, were fabricated and characterised for chemical, mechanical, swelling, network parameters, as well as drug release and biocompatibility. HPLC-based analytical methods were employed for analysis of two molecules; ELISA was used to demonstrate bioactivity of ovalbumin. Results Regardless of PEGDA molecular weight or pore former composition all implants loaded with triamcinolone acetonide released significantly faster than those loaded with ovalbumin. Higher molecular weight PEGDA systems (700 Da) resulted in faster drug release of triamcinolone acetonide than their 250 Da counterpart. All ovalbumin released over the 56-day time period was found to be bioactive. Increasing PEGDA molecular weight resulted in increased system swelling, decreased crosslink density (Ve), increased polymer-water interaction parameter (χ), increased average molecular weight between crosslinks (Mc) and increased mesh size (ε). SEM studies showed the porosity of implants increased with increasing PEGDA molecular weight. Biocompatibility showed both PEGDA molecular weight implants were non-toxic when exposed to retinal epithelial cells over a 7-day period. Conclusion Photocrosslinked PEGDA implant based systems are capable of controlled drug release of both small and large drug molecules through adaptations in the polymer system network. We are currently continuing evaluation of these systems as potential sustained drug delivery devices.