Enhancement in brain uptake of Vitamin D3 nanoemulsion for treatment of cerebral ischemia: Formulation, Gamma scintigraphy and efficacy study in transient middle cerebral artery occlusion rat models
Journal of Microencapsulation https://doi.org/10.1080/02652048.2020.1801870
Mukesh Kumar,Dhruv Kumar Nishad,Anoop kumar,Aseem Bhatnagar,Ritu Karwasra,Kushagra Khanna, show all
The study used radioactive Vitamin D
Increased Vitamin D to the brain might help prevent/treat:
strokes, Alzheimer's, Parkinson's, Epilepsy, etc.
Normally the blood-brain barrier somewaht restricts Vitamin D from getting to the brain
The nose is directly connected to the brain – no blood-brain barrier
Founder of VitaminDWiki has been inhailing Vitamin D nanoemulsion through his nose and mouth since 2017
The lungs can activate vitamin D locally – a Vitamin D inhaler may help lungs – Aug 2016
Nanoemulsion Vitamin D may be a substantially better form
The nose, in addition to the lung, can activate Vitamin D locally.
A nose, surprisingly, has MORE square meters of surface area than a lung
Aim: For the treatment of cerebral ischemia, Vitamin-D3 loaded nanoemulsion were developed.
Method: Tween 20 and polyethylene glycol were choosen as surfactant/co-surfactant, while oleic acid as oil phase. The formulation was characterized for various in-vitro parameters. Targeting efficiency was investigated through radiometry, gamma scintigraphy and efficacy was studied in transient middle cerebral artery occlusion (MCAo) rat model.
Result: Vitamin D3-Nanoemulsion showed a mean size range of 49.29 ± 10.28 nm with polydispersity index 0.17 ± 0.04 and zeta potential 13.77mV. Formulation was found stable during thermodynamic stability study and permeated within 180 min through sheep nasal mucosa (permeation coefficient 7.873 ± 0.884 cm/h). Gamma scintigraphy and radiometry assay confirmed better percentage deposition (2.53 ± 0.17%) of 99mTc-Vitamin D3-Nanoemulsion through nasal route compared to IV administered 99mTc-Vitamin D3 solution (0.79 ± 0.03%). Magnetic Resonance Imaging (MRI) of the ischemic model confirmed better efficacy of Vitamin D3-Nanoemulsion.
Conclusion: This work demonstrated better permeation, deposition and efficacy of VitaminD3-Nanoemulsion through intranasal route.
- Gupta, A., et al. 2016. Effect of Vitamin D and calcium supplementation on ischaemic stroke outcome: a randomized controlled open-label trial. ... ClinicalPractice. 70(9), 764-770.
- Gupta, R., et al. 2018. Recent Advances in Formulation Strategies for Vitamin D. AAPS PharmSciTech. 20(1), 11.
- Gupta, S., et al. 2017. Neuroprotective effect of lercanidipine in occlusion model of stroke in rats. Experimental Necrology. 288, 25-37 Guttoff, M., et al. 2015. Formation of vitamin D nanoemulsion-ba spontaneous emulsification: factors affecting 117-122.
- Hossmann, K.A., 1994. Viability thresholds and the penumbra of focal Neurology. 36(4), 557-565.
- Illum, L., 2003. Nasal drug delivery一possibilities, problems and solutions. Journal of Controlled Release. 87(1-3), 187-198.
- Kumar, M., et al. 2008. Intranasal nanoemulsion based brain targeting drug delivery system of risperidone. International Journal of Pharmaceutics. 285-291.
- Lakhan, S.E., Kirchgessner, A., Hofer, M., 2009. Inflammatory mechanisms in ischemic stroke: therapeutic approaches. Journal of Translational Medicine. 7(1), 97.
- Lawrence, M. J. and Rees, G. D., 2000.Microemulsion-based media as novel drug delivery systems. Advance Drug Delivery Review. 45(1), 89-121.
- Liu, W., et al. 2018. The anti -Inflammatory Effects of Vitamin D in Tumorigenesis. International Journal of Molecular Sciences. 19(9), 2136.
- Li, J., et al. 2018. Preparation optimization and stirage stability of nanoemulsion based lutein delivery systems. Journal o/micoencapsulation. 35 (6), 570-583.
- Majumdar, V., et al. 2015. Vitamin D status, hypertension and ischemic stroke: a clinical perspective. Journal of Human Hypertension. 29(11), 669-674.
- Marklund, S. and Marklund, G., 19 autoxidation of pyrogallol and a conv of Biochemistry. 47 (3), 469-474.
- Markisic, M., et al. 2017. The Impact of Homocysteine, Vitamin B12, and Vitamin D Levels on Functional Outcome after First-Ever Ischaemic Stroke. Biomed Research /nternational. 2017,1-6.
- Md, S., et al. 2013. Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: Pharmacodynamic, Pharmacokinetic and Scintigraphy study in mice model. European Journal of Pharmaceutical Science. 48 (3), 393-405.
- Milanlioglu, A., et al. 2015. Serum antioxidant enzymes activities and oxidative stress levels in patients with acute ischemic stroke: influence on neurological status and outcome. Wien
- Musa, S.H., et al. 2013. Formulation optimization of palm kernel oil esters nanoemulsion- loaded with chloramphenicol suitable for meningitis treatment.
- Ohkawa, H., et al. 1979. Assay of lipid peroxides in animals tissue by thiobarbituric acid reaction. AnalyticalBiochemistr;y. 95 (2), 351-358.
- Pangeni, R., et al. 2014. Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress. Nanotechnology. 25(48), 485502.
- Note: Resveratrol increases the activation of the Vitamin D Receptor
- Punj, A., et al. 2017. Estimation of Antioxidant Levels in Saliva and Serum of Chronic Periodontitis Patients with and without Ischemic Heart Disease. International Journal of Dentistry. 1-9.
- Sharma, N., et al. 2018. Development a] graecum (Fenugreek) polysaccharid 2571.
- • Shi, Y., et al. 2015. Development optimization and evaluation of emodin loaded nanoemulsion prepared by ultrasonic emulsification. Journal of Drug Delivery Science and Technology. 27, 46-55.
- Silva, H.D., et al.2011. Nanoemulsions for Food Applications: Development and Characterization. FoodBio ocess Technology. 5(3), 854-867.
- Thakkar, H.P., et al. 2015. Formulation and evaluation of Itraconazole nanoemulsion for enhanced oral bioavailability. Journal of microencapsulation. 32 (6) 559-569.
- Tran, T.H., et al. 2014. Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability. Journal of Pharmaceutical Sciences. 103(3), 840-852.
- Note: Quercetin increases the activation of the Vitamin D Receptor
- Vyas, T., et al. 2005. Intranasal Drug Delivery for Brain Targeting. Current Drug Delivery.
- Wei, Z.N. and Kuang, J.G., 2018. Vitamin D deficiency in relation to the poor functional outcomes in nondiabetic patients with ischemic stroke. Bioscience Reports. 38(2), 1-32.
- Yu, H.L.et al. 2019. ESE1 expression correlates with neuronal apoptosis in the hippocampus after cerebralischemia/reperfusion injury. Neural Regeneration Research. 14(5), 41-849.
- Zhou, R.et al. 2018. Lower Vitamin D Status Is Associated with an Increased Risk of Ischemic Stroke: A Systematic Review and Meta-Analysis. Nutrients. 10(3) 277.