The development of siRNA-based therapies for the treatment of severe ocular diseases is being proposed as a promising therapeutic option for the treatment of severe ocular diseases. Unfortunately, the capacity of siRNA molecules to overcome the multiple protective barriers of the eye is very limited. The specific objective of this work was to develop multiplayer protamine NCs loading high amounts of siRNA (up to 5 mg/mL) for ocular topical administration. Different preparation methods and compositions were studied for the development of NCs complying with the requirements of drug loading and release and also in terms of stability. Among the multiple formulations developed, one of them led to acceptable silencing results in vitro and showed the ability to interact efficiently with the rabbits’ corneal epithelium.
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