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

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.

Investigation of the Pro-active Role of Alpha Amyrin Nanoemulsions in Quashing Neurodegeneration, Excitotoxicity, and Neuronal Inflammation-A Combined in vivo and in silico Approach

“…28 The animals were tested using an elevated plus maze for their neurobehavioral changes on day 21 and day 42. The dose and route, 29,30 of administration of isolated alpha amyrin were selected based on a pilot study and earlier literature.…”

Fabricating Polymer/Surfactant/Cyclodextrin Hybrid Particles for Possible Nose-to-Brain Delivery of Ropinirole Hydrochloride: In Vitro and Ex Vivo Evaluation

“…In recent years, researchers have explored the potential of the nasal route of administration as an alternative approach for managing Parkinson's disease [11][12][13][14][15]. Lin et al [13] fabricated a thermoresponsive gel containing 20% P407, 18% poloxamer 188, 1% polyethylene glycol 6000 and 3% hydroxypropyl-β-CD (HPβCD) for the intranasal administration of an antiparkinsonian drug, rhynchophylline.…”

“…Lin et al [13] fabricated a thermoresponsive gel containing 20% P407, 18% poloxamer 188, 1% polyethylene glycol 6000 and 3% hydroxypropyl-β-CD (HPβCD) for the intranasal administration of an antiparkinsonian drug, rhynchophylline. Imran et al [12] developed a mucoadhesive microemulsion for the efficient delivery of silymarin, enhancing behavioral and biochemical parameters and reducing inflammatory markers in treated rats. Kim et al [14] presented an innovative approach to enhance mitochondrial function and provide protection against Parkinson's disease through the nasal route of administration.…”

Chitosan Biomaterials: Advances and Challenges

“…A challenging topic studied lately has been the intranasal administration of drugs, due to its advantages. Many drug administration systems are based on chitosan or its derivatives, such as gels for the intranasal administration of antihistamines (loratadine and chlorpheniramine) [10]; insulin [11]; liposomes and nanoemulsions for the administration of a derivative of Dehydroepiandrosterone (DHEA) [12]; microemulsion with silymarin for the treatment of Parkinson's disease [13]; nanoparticles with galantamine [14] or ropinirole [15]; and nanocrystals with memantine for the treatment of Alzheimer's disease [16].…”