In situ forming photocrosslinked biodegradable implants for sustained delivery of proteins

Abstract

Purpose : This study investigated the potential of using poly(ethylene glycol) diacrylate (PEGDA) and poly(lactic-co-glycolic acid) (PLGA) based in situ forming photocrosslinked implants for sustained delivery of proteins.

Methods : Gels were formulated by mixing PEGDA, PLGA, photoinitiator and protein – ovalbumin (OVA, 43 kDa), bovine serum albumin (BSA, 67 kDa), or bevacizumab (BEV, 150 kDa). The gels were injected in saline and exposed to UV light for photcrosslinking to form implants. The morphology of the implants was studied by using scanning electron microscopy (SEM). In vitro drug release was performed in phosphate-buffered saline (PBS, pH 7.4). The released BSA/BEV was quantified by a size-exclusion chromatography-high performance liquid chromatography (SEC-HPLC) and OVA was quantified via Micro-BCA assay.

Results : The implants containing 30 w/w % PLGA and crosslinked for 5 min, provided a long-term controlled release of BSA, with nearly 86% BSA released in 200 days. On the other hand, nearly 29% and 60% OVA was released from implants crosslinked for 2.5 min and 30 sec, respectively. The high molecular weight BEV (150 kDa) showed 41% to 100% release from implants crosslinked for 2.5 min and 30 sec, in 140 days (Fig. 1). Likewise, similar trend was observed for OVA release from the implants. The drug release rate of the implants can be adjusted by varying the concentration of the photoinitiator, formulation composition and crosslinking time. In specific, implants prepared with higher concentration of photoinitiator and longer crosslinking time can sustain the drug release for longer periods of time.

Conclusions : The novel in situphotocrosslinked implants can provide sustained release of proteins for 4-6 months. This new platform drug delivery technology has significant potential for sustained intravitreal/intraocular delivery of therapeutic proteins to treat neovascular ocular diseases, such as proliferative diabetic retinopathy and neovascular age-related macular degeneration.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.