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Mefenamic Acid Loaded and TPGS Stabilized Mucoadhesive Nanoemulsion for the Treatment of Alzheimer's Disease:
Anmol Dogra1,2, Ramandeep Singh Narang3, Tajpreet Kaur4
1I.K.G Punjab Technical University, Kapurthala, Punjab, India.
Abstract:
Alzheimer's disease (AD) is a very common disorder that affects the elderly. There are relatively few medications that can be used orally or as a suspension to treat AD. A mucoadhesive (o/w) nano emulsion of mefenamic acid was made by adding Carbopol 940P to the optimised drug nanoemulsion using distilled water as the aqueous phase (6%); Solutol HS: tween 20 (3.6%) as the surfactant and co-surfactant; and clove oil: TPGS (0.4%) as the oil phase and mefenamic acid as the drug (2.8 mg/ml). The mucoadhesive nanoemulsion (S40.5%w/v) had a particle size of 91.20 nm, polydispersity index of 0.270, and surface charge of - 12.4 mV. Significantly higher (p < 0.001) drug release (89.37%) was observed for mucoadhesive drug formulation in comparison to mucoadhesive drug suspension (25.64%) at 8 h. The ex vivo nasal permeation of 83.03% in simulated nasal fluid and 85.71% in artificial cerebrospinal fluid was observed. The percent inhibition and inhibitory concentration (IC50) of mucoadhesive drug nanoemulsion were found to be 91.57 ± 2.69 and 6.76 respectively. Higher cell viability on glioblastoma cells (85-80%) was researched for mucoadhesive nanoemulsion as compared to drug suspension (80-70%). Significantly higher (p < 0.001) drug absorption and Cmax (491.94 ± 24.13 ng/ml) of mucoadhesive drug nanoemulsion were observed than mucoadhesive drug suspension (107.46 ± 11.46 ng/ml) at 8 h. The stability studies confirmed that the formulation was stable at 40°C ± 2°C and 75 ± 5% RH. The authors concluded that the mucoadhesive mefenamic acid-loaded nanoemulsion may be an effective technique for treating Alzheimer's disease by intranasal route.
Insights
This study developed a novel mucoadhesive nanoemulsion for mefenamic acid delivery to treat Alzheimer's disease (AD). The nanoemulsion showed enhanced drug release, nasal permeation, and absorption compared to suspension, suggesting a promising intranasal treatment strategy for AD.
Area of Science:
- Pharmaceutical Sciences
- Nanotechnology
- Neuroscience
Background:
- Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the elderly population.
- Limited oral and suspension formulations exist for AD treatment.
- Developing novel drug delivery systems is crucial for improving therapeutic efficacy.
Purpose of the Study:
- To formulate and characterize a mucoadhesive nanoemulsion of mefenamic acid for potential Alzheimer's disease treatment.
- To evaluate the in vitro and ex vivo performance of the nanoemulsion.
- To assess the safety and efficacy of the nanoemulsion compared to a drug suspension.
Main Methods:
- Preparation of an oil-in-water (o/w) nanoemulsion using mefenamic acid, Carbopol 940P, Solutol HS, Tween 20, clove oil, and TPGS.
- Characterization of nanoemulsion properties including particle size, polydispersity index, and surface charge.
- In vitro drug release studies, ex vivo nasal permeation assays, and cell viability tests on glioblastoma cells.
- In vivo pharmacokinetic studies to determine drug absorption and Cmax.
Main Results:
- The mucoadhesive nanoemulsion exhibited a particle size of 91.20 nm and a negative surface charge (-12.4 mV).
- Significantly higher drug release (89.37%) and nasal permeation (83.03% in SBF, 85.71% in aCSF) were observed for the nanoemulsion compared to suspension.
- The nanoemulsion demonstrated potent anti-inflammatory activity (91.57% inhibition) and superior cell viability (85-80%) on glioblastoma cells.
- Drug absorption and Cmax were significantly higher (491.94 ng/ml) for the nanoemulsion than the suspension (107.46 ng/ml).
Conclusions:
- The developed mucoadhesive mefenamic acid nanoemulsion is a stable and effective formulation.
- Intranasal delivery of this nanoemulsion offers a promising therapeutic approach for Alzheimer's disease.
- This novel nanoemulsion system enhances drug bioavailability and therapeutic potential for AD treatment.
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