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ApoE3 Anchored Liposomal Delivery of Rivastigmine for Brain Delivery: Formulation, Characterization, and In Vivo Pharmacokinetic Evaluation

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Abstract

Rivastigmine hydrogen tartrate (RHT) is an acetylcholinesterase (AChE) inhibitor used in the management of Alzheimer’s disease (AD). RHT is a BCS class-I drug that undergoes significant first-pass metabolism. Permeating a hydrophilic drug through the brain remains a major challenge in brain delivery. In this study, the RHT was incorporated inside the hydrophilic core of liposomes (LPS) and then coated with the ApoE3. ApoE3-coated RHT-loaded liposomes (ApoE3-RHT-LPS) were fabricated through the thin film hydration method using DSPE-PEG. The coating of LPS with ApoE3 enhances brain uptake and improves Aβ clearance. The results obtained from the physicochemical characterization demonstrated that ApoE3-RHT-LPS shows a particle size of 128.6 ± 2.16 nm and a zeta potential of 16.6 ± 1.19. The % entrapment efficiency and % drug loading were found to be 75% and 17.84%, respectively. The data obtained from TEM and SEM studies revealed that the particle size of the LPS was less than 200 nm. An in vitro AChE assay was performed, and the results demonstrated the AChE inhibitory potential of ApoE3-RHT-LPS. Through the intravenous route, an in vivo pharmacokinetic study of formulation displayed improved brain uptake of RHT by ~ 1.3-fold than pure RHT due to ApoE3 coating. In vivo, biodistribution studies in vital organs suggested that the biodistribution of RHT to the liver was significantly reduced (p < 0.001), signifying an increase in the drug’s half-life and blood circulation time. All research findings suggested that ApoE3 coating and LPS strategy are proven effective for improving the brain uptake of RHT designed for the management of AD.

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Data Availability

The data that support the findings of this study are openly available with the author in the repository.

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Acknowledgements

The authors would like to acknowledge the research funding support by the Department of Pharmaceuticals (DoP), Ministry of Chemicals and Fertilizers, Govt. of India, to National Institute of Pharmaceutical Education and Research (NIPER) Raebareli, India. The Institutional Animal Ethics Committee No is NIPER/RBL/118/AUG 2023. The NIPER-R communication number for the research article is NIPER-R/Communication/465. 

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Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Raebareli, Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, Lucknow, 226002, India

    Pooja Khairnar, Ajit Singh, Kailash Ahirwar & Rahul Shukla

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  1. Pooja Khairnar
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  2. Ajit Singh
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Contributions

Dr. Rahul Shukla: supervision, conceptualization, methodology, and investigation; Pooja khairnar: writing original draft, methodology, validation, visualization, data curation, analysis, and data interpretation; Ajit Singh: editing and investigation; and Kailash Ahirwar: editing and investigation.

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Correspondence to Rahul Shukla.

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Khairnar, P., Singh, A., Ahirwar, K. et al. ApoE3 Anchored Liposomal Delivery of Rivastigmine for Brain Delivery: Formulation, Characterization, and In Vivo Pharmacokinetic Evaluation. AAPS PharmSciTech 24, 223 (2023). https://doi.org/10.1208/s12249-023-02684-8

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