A Cell-Based Drug Delivery System Using Collagen-Alginate Composite Matrix: In Vitro And In Vivo Studies

1. Amy Lo^1,2
2. Chi-Hung Wong¹
3. Shen Nian¹
4. Pik-To Cheung³
5. Barbara Chan⁴
6. David Wong^1,2

¹Eye Institute, The University of Hong Kong, Hong Kong
²Research Center of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong
³Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
⁴Department of Mechanical Engineering, The University of Hong Kong, Hong Kong

Purpose: Diseases such as diabetic retinopathy are leading causes of blindness and clinically effective neuroprotective drugs are much desired. Glial-derived neurotrophic factor (GDNF) is highly promising with proven neuroprotective properties. A challenge is how to bring this large molecule across blood-ocular barrier. One delivery method is intravitreal injection; yet, GDNF's short half life (30-60min) means repeated injection, which is not feasible. Another is by GDNF-loaded biodegradable micro-spheres, but in a non-sustainable manner. As eye diseases are often chronic, a prolonged neuroprotection is preferred. We aimed to engineer a cell-based device for sustained drug delivery using collagen-alginate composite matrix and investigate GDNF secretion from the encapsulated cells in vitro and in vivo.

Methods: Collagen-alginate composite matrix encapsulating GDNF-secreting human embryonic kidney (HEK293) cells was maintained with culture medium. For in vitro measurements, the medium was harvested 7 or 14 days later. For in vivo investigation, the matrix was injected into vitreous cavity of Sprague-Dawley rat eyes which was harvested 7 and 14 days later. The amount of GDNF present in culture medium and vitreous were quantified by ELIZA.

Results: The levels of GDNF secreted in vitro and in vivo were comparable. A sustainable, stable GDNF secretion was attained in both conditions with the amount reaching a therapeutic level. Cells were found immobilized inside collagen-alginate matrix.

Conclusion: Our cell-based device delivered GDNF at a therapeutic level continuously for up to 2 weeks without cell leakage. This study contributes to development of intraocular drug delivery device for future therapeutics.