Preparation, characterisation, pharmacokinetics and distribution of esculin microspheres administered via intravitreal injection into rabbit brain

Abstract

1. This study explored the distribution of esculin microspheres in rabbit brain tissue following intravitreal injection and investigated the possibility of direct entry of the drug into the brain through the eye, to develop a formulation with enhanced therapeutic efficacy against Parkinson’s disease.

2. Chitosan microspheres of esculin were prepared via an emulsification cross-linking method and their characteristics were evaluated, including angle of repose, bulk density, and swelling ratio. Furthermore, the pharmacokinetic parameters and brain tissue distribution in rabbits were compared among groups administered esculin eye drops, intravitreal esculin solution, and intravitreal esculin microspheres, to determine whether esculin could enter the brain through an ocular route.

3. The results showed that the prepared esculin microspheres were spherical and had good fluidity. Notably, intravitreal administration enhanced the area under the curve (AUC) of esculin in the thalamus. Delivery through microspheres prolonged the drug retention time in both rabbit plasma and brain tissues, as well as the brain-targeting efficiency of esculin.

4. The collective findings indicated that there may be a direct eye-brain pathway facilitating enter of esculin microspheres into brain tissue after intravitreal injection, supporting the utility of intravitreal esculin microspheres as an effective therapeutic formulation for Parkinson’s disease, a long-term chronic condition.

Keywords:

• Esculin
• microspheres
• intravitreal injection
• brain targeting
• Parkinson’s disease

Acknowledgments

The authors gratefully acknowledge support from the Anhui Provincial Natural Science Foundation (grant number 2108085MH312) and thank The Charlesworth Group for providing help with language editing.

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

Data will be made available on request.

Additional information

Funding

This work was supported by the Anhui Provincial Natural Science Foundation (grant number 2108085MH312).