Intranasal Delivery of a Silymarin Loaded Microemulsion for the Effective Treatment of Parkinson's Disease in Rats: Formulation, Optimization, Characterization, and In Vivo Evaluation

Mohd Imran; Mazen Almehmadi; Ahad Amer Alsaiari; Mehnaz Kamal; Mohammed Kanan Alshammari; Mohammed Omar Alzahrani; Faisal Khaled Almaysari; Abdulrahman Omar Alzahrani; Ahmed Faraj Elkerdasy; Sachin Kumar Singh

doi:10.3390/pharmaceutics15020618

Intranasal Delivery of a Silymarin Loaded Microemulsion for the Effective Treatment of Parkinson's Disease in Rats: Formulation, Optimization, Characterization, and In Vivo Evaluation

Pharmaceutics. 2023 Feb 12;15(2):618. doi: 10.3390/pharmaceutics15020618.

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.
² Department of Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁴ Department of Pharmaceutical Care, Rafha Central Hospital, North Zone, Rafha 76312, Saudi Arabia.
⁵ Faculty of Pharmacy, King Abdulaziz University, Jeddah 42210, Saudi Arabia.
⁶ Faculty of Medicine, King Abdulaziz University, Jeddah 42210, Saudi Arabia.
⁷ Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, University of Sadat City, Sadat City 32897, Egypt.
⁸ School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India.
⁹ Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia.

Abstract

A mucoadhesive microemulsion of lipophilic silymarin (SLMMME) was developed to treat Parkinson's disease (PD). Optimization of the SLM microemulsion (ME) was performed using Central Composite Design (CCD). The composition of oil, surfactant, co-surfactant, and water was varied, as per the design, to optimize their ratio and achieve desirable droplet size, zeta potential, and drug loading. The droplet size, zeta potential, and drug loading of optimized SLMME were 61.26 ± 3.65 nm, -24.26 ± 0.2 mV, and 97.28 ± 4.87%, respectively. With the addition of chitosan, the droplet size and zeta potential of the developed ME were both improved considerably. In vitro cell toxicity investigations on a neuroblastoma cell line confirmed that SLMMME was non-toxic and harmless. In comparison to ME and drug solution, mucoadhesive ME had the most flow through sheep nasal mucosa. Further, the in vitro release showed significantly higher drug release, and diffusion of the SLM loaded in MEs than that of the silymarin solution (SLMS). The assessment of behavioral and biochemical parameters, as well as inflammatory markers, showed significant (p < 0.05) amelioration in their level, confirming the significant improvement in neuroprotection in rats treated with SLMMME compared to rats treated with naïve SLM.

Keywords: central composite design; lipophilic drug; microemulsion; mucoadhesion; neurodegenerative disease; zeta potential.

Grants and funding

This study is supported via funding from Prince Sattam bin Abdulaziz University project number (PSAU/2023/R/1444).