Fabrication and characterisation of implants for intraocular delivery of triamcinolone acetonide

Abstract

Purpose : This study involves fabrication and characterisation of poly(ethylene glycol) diacrylate (PEGDA)-based photocrosslinked implants for sustained ocular delivery of triamcinolone acetonide (TA).

Methods : Gel formulations were optimised to contain 2.5% w/w TA, 10% w/w of pore forming agent and 0.1% w/w photoinitiator in required quantity of PEGDA (250 or 700 Da). Gels were casted into films and photocrosslinked to form implants. Prepared implants were evaluated for dynamic and equilibrium swelling, mechanical strength (namely compressibility) and surface porosity (via scanning electron microscopy, SEM)). And, in vitro drug release in phosphate-buffered saline (PBS).

Results : Decreasing PEGDA M_w resulted in slower drug release from these implants. All PEGDA with M_w of 250 Da showed a significantly slower release rate than those prepared with 700 Da. For example, PEGDA 700 implants exhibited 50% or greater release within first 10 days compared to PEGDA 250 implants that released only 8%. The addition of various pore forming agents results in faster drug release regardless of PEGDA M_w. By Day 10, gelatin provided the fastest release from PEGDA M_w700 implants (97.66%) and sodium bicarbonate provided the greatest release from PEGDA M_w250 implants (25.28%). Release data is supported by SEM images that show increased porosity in implants composed of higher M_w PEGDA and pore forming agents. For e.g., Fig.1 shows the pores formed in M_w700 implant loaded with maltose.
The effect of varying pore former and M_w of PEGDA on implant swelling was also investigated, it was observed that increase in M_w of PEGDA has significantly increased % swelling. Mechanical strength of the implants measured after 24h in PBS, was also affected by PEGDA M_w and pore former loading. For e.g. mannitol loaded M_w250 implants required 8.70N of force compared to M_w700 implants that required only 0.27N of force.

Conclusions : Photocrosslinked PEGDA implants can provide sustained delivery of TA. This study showed varying PEGDA M_w and/or the addition of pore forming agents can affect drug release from the implant system and alter its mechanical and swelling properties. Thus indicating that this delivery system has the capability to control the drug release by varying the implant composition.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Fig. 1 SEM image of pore formation in PEGDA M_w700 implant loaded with maltose taken after 24h in PBS