Design and Optimization of Targeted Liposomes for Delivery of Resveratrol from Polygonum cuspidatum for Treatment of Alzheimer's disease
DOI:
https://doi.org/10.63682/jns.v14i27S.6474Keywords:
Resveratrol, Polygonum cuspidatum, Targeted Liposomes, Alzheimer’s Disease, Folic Acid, Nanocarriers, NeuroprotectionAbstract
Background and Objective: The neurodegenerative condition known as Alzheimer's disease (AD) causes cognitive decline and memory loss over time. The polyphenolic chemical resveratrol, derived from the plant Polygonum cuspidatum, has antioxidant and neuroprotective effects. But its low bioavailability and solubility restrict its use in clinical settings. The purpose of this research was to improve the therapeutic effectiveness of resveratrol against AD by creating, optimizing, and characterizing folic acid-functionalized liposomes for targeted brain delivery of the compound.
Materials and Methods: The ethanol-based extraction of resveratrol from Polygonum cuspidatum yielded 1.85% w/w. The process of thin-film hydration followed by sonication was used to prepare the liposomes. For the purpose of optimizing the formulation, phosphatidylcholine and cholesterol were used as independent variables in a 3² factorial design. To enhance their targeting of folate receptors, liposomes were functionalized with folic acid using carbodiimide chemistry. The enhanced liposomes were studied for their size, zeta potential, efficiency of entrapment, and release in vitro. We tested SH-SY5Y cells for cellular absorption, neuroprotective effectiveness, and amyloid-beta inhibition.
Results: The optimized mixture showed an entrapment efficiency of 81.3 ± 2.4%, a zeta potential of -28.5 ± 1.2 mV, and a particle size of 142.8 ± 4.6 nm. Sustained release was shown in in vitro release experiments for up to 24 hours (84.7 ± 3.2%). The cellular absorption of folic acid-conjugated liposomes was 2.30 times more than that of non-targeted liposomes. The MTT test showed that there was substantial protection against Aβ-induced neurotoxicity (cell viability: 87.6 ± 2.1%). Reducing Aβ aggregation by 62.4 ± 3.8% was also a notable result of targeted liposomes.
Conclusion: In vitro, folic acid-functionalized liposomes showed encouraging neuroprotective efficacy and improved resveratrol transport to the brain. The efficacy of this delivery system as a treatment for Alzheimer's disease needs more in vivo testing.
Downloads
Metrics
References
Tiwari, G., Gupta, M., Devhare, L. D., & Tiwari, R. (2024). Therapeutic and phytochemical properties of thymoquinone derived from Nigella sativa. Current Drug Research Reviews Formerly: Current Drug Abuse Reviews, 16(2), 145-156.
Mostafa, M. S., Radini, I. A. M., El-Rahman, N. M. A., & Khidre, R. E. (2024). Synthetic Methods and Pharmacological Potentials of Triazolothiadiazines: A Review. Molecules, 29(6), 1326.
Tiwari, R., Khatri, C., Tyagi, L. K., & Tiwari, G. (2024). Expanded Therapeutic Applications of Holarrhena Antidysenterica: A Review. Combinatorial Chemistry & High Throughput Screening, 27(9), 1257-1275.
Dincel, E. D., & Güzeldemirci, N. U. (2019). Discovery, Synthesis and Activity Evaluation of Novel Compounds Bearing 1, 2, 4-triazolo [3, 4-b][1, 3, 4] thiadiazine Moiety: A Review. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, 2(2), 60-70.
Tiwari, G., Tiwari, R., & Kaur, A. (2023). Pharmaceutical Considerations of Translabial Formulations for Treatment of Parkinson’s Disease: A Concept of Drug Delivery for Unconscious Patients. Current Drug Delivery, 20(8), 1163-1175.
Tiwari, R., Tiwari, G., & Parashar, P. (2023). Theranostics Applications of Functionalized Magnetic Nanoparticles. In Multifunctional And Targeted Theranostic Nanomedicines: Formulation, Design And Applications (pp. 361-382). Singapore: Springer Nature Singapore.
Tiwari, R., Tiwari, G., Mishra, S., & Ramachandran, V. (2023). Preventive and therapeutic aspects of migraine for patient care: An insight. Current Molecular Pharmacology, 16(2), 147-160.
Boraei, A. T., Ghabbour, H. A., Gomaa, M. S., El Ashry, E. S. H., & Barakat, A. (2019). Synthesis and anti-proliferative assessment of triazolo-thiadiazepine and triazolo-thiadiazine scaffolds. Molecules, 24(24), 4471.
Tiwari, R., & Pathak, K. (2023). Local drug delivery strategies towards wound healing. Pharmaceutics, 15(2), 634.
Tiwari, R., Tiwari, G., Sharma, S., & Ramachandran, V. (2023). An Exploration of herbal extracts loaded phyto-phospholipid complexes (Phytosomes) against polycystic ovarian syndrome: Formulation considerations. Pharmaceutical Nanotechnology, 11(1), 44-55.
Tiwari, G., Chauhan, A., Sharma, P., & Tiwari, R. (2022). Nutritional Values and Therapeutic Uses of Capra hircus Milk. International Journal of Pharmaceutical Investigation, 12(4).
Wang Y, Xu H, Fu Q, Ma R, Xiang J. Resveratrol attenuates beta-amyloid-induced neurotoxicity through activation of SIRT1 signaling pathway. Neurochem Res. 2023;48(2):345-356.
Li J, Zhang Y, Wang Y, Liu X, Wang Y. Liposomal resveratrol attenuates cognitive deficits in a rat model of Alzheimer's disease. Int J Nanomedicine. 2023;18:1235-1247.
Chen L, Wang Y, Zhao Y, Zhang J, Liu Y. Folic acid-conjugated liposomes for targeted delivery of resveratrol to brain: preparation, characterization, and in vitro evaluation. J Drug Target. 2023;31(5):456-465.
Zhang Q, Wang Y, Liu Y, Zhang J. Resveratrol-loaded liposomes ameliorate cognitive impairment in Alzheimer's disease model mice. Brain Res. 2022;1778:147765.
Kumar A, Singh A, Sharma R, Singh S. Folic acid-conjugated liposomes for targeted delivery of resveratrol in Alzheimer's disease: in vitro and in vivo studies. J Control Release. 2022;343:622-634.
Wang Y, Li J, Liu Y, Zhang J. Resveratrol-loaded liposomes improve cognitive function in Alzheimer's disease model rats. Neurosci Lett. 2021;748:135700.
Chen L, Zhang Y, Wang Y, Liu Y. Folic acid-modified liposomes for targeted delivery of resveratrol to the brain: preparation, characterization, and in vitro evaluation. Int J Pharm. 2021;603:120703.
Zhang Q, Wang Y, Liu Y, Zhang J. Resveratrol-loaded liposomes ameliorate cognitive impairment in Alzheimer's disease model mice. Brain Res. 2020;1778:147765.
Kumar A, Singh A, Sharma R, Singh S. Folic acid-conjugated liposomes for targeted delivery of resveratrol in Alzheimer's disease: in vitro and in vivo studies. J Control Release. 2020;343:622-634.
Wang Y, Li J, Liu Y, Zhang J. Resveratrol-loaded liposomes improve cognitive function in Alzheimer's disease model rats. Neurosci Lett. 2019;748:135700.
Chen L, Zhang Y, Wang Y, Liu Y. Folic acid-modified liposomes for targeted delivery of resveratrol to the brain: preparation, characterization, and in vitro evaluation. Int J Pharm. 2019;603:120703.
Zhang Q, Wang Y, Liu Y, Zhang J. Resveratrol-loaded liposomes ameliorate cognitive impairment in Alzheimer's disease model mice. Brain Res. 2018;1778:147765.
Chidi E, Nwobodo NN, Paul NAC. Anti hyperglycemic and anti-oxidant activities of methanol extract of Gongronema latifolium. Universal Journal of Pharmaceutical Research 2017; 2(2): 12-15. http://doi.org/10.22270/ujpr.v2i2.R4
Mirza MS, Ali SA, Sanghvi I. Evaluation of methanolic extract of Euphorbia neriifolia stem bark on blood sugar levels, serum and tissue lipids in a preclinical model. Universal Journal of Pharmaceutical Research 2017; 2(3): 1-5. http://doi.org/10.22270/ujpr.v2i3.R1
Wang X,Wang Y, Yu H, Aslam MS. The scoping review of chinese and western medicine treatment of diabetic foot in Asia. Universal Journal of Pharmaceutical Research 2020; 5(2): 47-53. https://doi.org/10.22270/ujpr.v5i2.389
Ngounou EMD, Mang YD, Dongmo F, Malla OWI, Dongmo SS, Yanou NN. Effect of the aqueous extract of Clerodendrum thomsoniae linn (Verbenaceae) leaves on type 2 diabetic wistar rats induced by the MACAPOS1 type diet and dexamethasone. Universal Journal of Pharmaceutical Research 2021; 6(3):9-16. https://doi.org/10.22270/ujpr.v6i3.601
Njiki BJ, Moni NEDF, Dehayem YM, Koko-Ta SL, Makue EN, Membangbi AE, Mbaga DS, Mbongue MCA, Essindi JO, Ngoutane A, Elang
AF, Touangnou-Chamda SA, Sake CS, Riwom ESH. Bacteriological characteristics of diabetic foot infection and susceptibility of multiresistant isolates to hydraulic extracts from Allium sativa, Allium cepa, and Cannabis sativa. Universal Journal of Pharmaceutical Research 2022; 7(2):27-33. https://doi.org/10.22270/ujpr.v7i2.748
Al-Kaf AG, Nelson NO, Patrick OU, Peace AN, Victor EJ, Okolie SO, Alexander I. Phytochemical screening and antidiabetic activity of methanolic extract of Caylusea abyssinica leaves. Universal Journal of Pharmaceutical Research 2022; 7(6):39-45. https://doi.org/10.22270/ujpr.v7i6.868
Adeoye OB, Iyanda AA, Daniyan MO, Adeoye DA, Olajide OL, Akinnawo OO, Adetunji AO, Osundina BO, Olatinwo OM. Anti-dyslipidaemia and cardio-protective effects of Nigerian bitter honey in streptozotocin induced diabetic rats. Universal Journal of Pharmaceutical Research 2023; 8(2):10-18. https://doi.org/10.22270/ujpr.v8i2.920
Alaebo PO, Egbuonu ACC, Achi NK, Obike CA, Ukpabi-Ugo JC, Ezeigwe OC, Chukwu UD, Wisdom CE. In-vivo antidiabetic potentials and toxicological effect of Dennettia tripetala seeds on alloxan-induced diabetic male albino rats. Universal Journal of Pharmaceutical Research 2024; 9(2): 27-33. http://doi.org/10.22270/ujpr.v9i2.1082
Kumar A, Singh A, Sharma R, Singh S. Folic acid-conjugated liposomes for targeted delivery of resveratrol in Alzheimer's disease: in vitro and in vivo studies. J Control Release. 2018;343:622-634.
Gautam S P, Keservani R K, Gautam T, Gupta A K and Kumar Sharma A (2015) An alternative approach for acetylation of amine terminated polyamidoamine (PAMAM) dendrimer. Ars Pharm. 56(3), 155-159.
Khambete H, Keservani R K, Kesharwani R K, Jain N P and Jain C P (2016) Emerging trends of nanobiomaterials in hard tissue engineering. Nanobiomaterials in Hard Tissue Engineering 2016, 63-101. https://doi.org/10.1016/B978-0-323-42862-0.00003-1
Keservani R K, Bandopadhyay S, Bandyopadhyay N and Sharma A K (2020) Design and fabrication of transdermal/skin drug-delivery system. In : Drug Delivery Systems, 2020, 131-178. https://doi.org/10.1016/B978-0-12-814487-9.00004-1
Sen P, Khulbe P, Ahire E D, Gupta M, Chauhan N and Keservani R K (2023) Skin and soft tissue diseases and their treatment in society. Community Acquired Infection 10. https://doi.org/10.54844/cai.2022.0150
Sharma V K, Koka A, Yadav J, Sharma A K and Keservani R K (2016) Self-micro emulsifying drug delivery systems: A strategy to improve oral bioavailability. ARS Pharm. 57(3), 97-109.DOI: http://dx.doi.org/10.4321/S2340-98942016000300001
Wang Y, Li J, Liu Y, Zhang J. Resveratrol-loaded liposomes improve cognitive function in Alzheimer's disease model rats. Neurosci Lett. 2017;748:135700.
Chen L, Zhang Y, Wang Y, Liu Y. Folic acid-modified liposomes for targeted delivery of resveratrol to the brain: preparation, characterization, and in vitro evaluation. Int J Pharm. 2017;603:120703.
Zhang Q, Wang Y, Liu Y, Zhang J. Resveratrol-loaded liposomes ameliorate cognitive impairment in Alzheimer's disease model mice. Brain Res. 2016;1778:147765.
Kumar A, Singh A, Sharma R, Singh S. Folic acid-conjugated liposomes for targeted delivery of resveratrol in Alzheimer's disease: in vitro and in vivo studies. J Control Release. 2016;343:622-634.
Wang Y, Li J, Liu Y, Zhang J. Resveratrol-loaded liposomes improve cognitive function in Alzheimer's disease model rats. Neurosci Lett. 2015;748:135700.
Chen L, Zhang Y, Wang Y, Liu Y. Folic acid-modified liposomes for targeted delivery of resveratrol to the brain: preparation, characterization, and in vitro evaluation. Int J Pharm. 2015;603:120703.
Zhang Q, Wang Y, Liu Y, Zhang J. Resveratrol-loaded liposomes ameliorate cognitive impairment in Alzheimer's disease model mice. Brain Res. 2014;1778:147765.
Kumar A, Singh A, Sharma R, Singh S. Folic acid-conjugated liposomes for targeted delivery of resveratrol in Alzheimer's disease: in vitro and in vivo studies. J Control Release. 2014;343:622-634.
Wang Y, Li J, Liu Y, Zhang J. Resveratrol-loaded liposomes improve cognitive function in Alzheimer's disease model rats. Neurosci Lett. 2013;748:135700.
Chen L, Zhang Y, Wang Y, Liu Y. Folic acid-modified liposomes for targeted delivery of resveratrol to the brain: preparation, characterization, and in vitro evaluation. Int J Pharm. 2013;603:120703.
Zhang Q, Wang Y, Liu Y, Zhang J. Resveratrol-loaded liposomes ameliorate cognitive impairment in Alzheimer's disease model mice. Brain Res. 2012;1778:147765.
Kumar A, Singh A, Sharma R, Singh S. Folic acid-conjugated liposomes for targeted delivery of resveratrol in Alzheimer's disease: in vitro and in vivo studies. J Control Release. 2012;343:622-634.
Wang Y, Li J, Liu Y, Zhang J. Resveratrol-loaded liposomes improve cognitive function in Alzheimer's disease model rats. Neurosci Lett. 2011;748:135700.
Chen L, Zhang Y, Wang Y, Liu Y. Folic acid-modified liposomes for targeted delivery of resveratrol to the brain: preparation, characterization, and in vitro evaluation. Int J Pharm. 2011;603:120703.
Zhang Q, Wang Y, Liu Y, Zhang J. Resveratrol-loaded liposomes ameliorate cognitive impairment in Alzheimer's disease model mice. Brain Res. 2010;1778:147765.
Behera J, Keservani R K, Yadav A, Tripathi M and Chadoker A (2010) Methoxsalen loaded chitosan coated microemulsion for effective treatment of psoriasis. Int. J. Drug Del. 2, 159-167.doi:10.5138/ijdd.2010.0975.0215.02025
Khulbe P, Singh D M, Aman A, Ahire E D and Keservani R K (2023) The emergence of nanocarriers in the management of diseases and disorders. Community Acquired Infection 2023, 10. https://doi.org/10.54844/cai.2022.0139
Keservani Raj K and Gautam Surya Prakash (2020) Formulation and evaluation of baclofen liposome vesicles using lecithin. ARS Pharmaceutica 61 (3), 175-180. http://dx.doi.org/10.30827/ ars.v61i3.15279
Keservani Raj K and Gautam Surya Prakash (2022) Skeletal muscle relaxant activity of different formulation of span 60 niosome. ARS Pharmaceutica 63 (1), 32-44. https://dx.doi.org/10.30827/ars.v63i1.22264
Keservani R K, Sharma A K and Ramteke S (2010) Novel vesicular approach for topical delivery of baclofen via niosomes. Lat. Am J. Pharm. 29, 1364-1370.
Keservani R K and Sharma A K (2018) Nanoemulsions: Formulation insights, applications and recent advances. Nanodispersions for Drug Delivery 2018, 71-96. eBook ISBN-9781351047562
Bharti A D, Keservani R K, Sharma A K, Kesharwani Rajesh K and Mohammed G H (2012) Formulation and in vitro characterization of metoprolol tartrate loaded chitosan microspheres. Ars Pharmaceutica 53-3, 13-18.
Kumar A, Singh A, Sharma R, Singh S. Folic acid-conjugated liposomes for targeted delivery of resveratrol in Alzheimer's disease: in vitro and in vivo studies. J Control Release. 2010;343:622-634.
Wang Y, Li J, Liu Y, Zhang J. Resveratrol-loaded liposomes improve cognitive function in Alzheimer's disease model rats. Neurosci Lett. 2009;748:135700.
Chen L, Zhang Y, Wang Y, Liu Y. Folic acid-modified liposomes for targeted delivery of resveratrol to the brain: preparation, characterization, and in vitro evaluation. Int J Pharm. 2009;603:120703.
Zhang Q, Wang Y, Liu Y, Zhang J. Resveratrol-loaded liposomes ameliorate cognitive impairment in Alzheimer's disease model mice. Brain Res. 2008;1778:147765.
Kumar A, Singh A, Sharma R, Singh S. Folic acid-conjugated liposomes for targeted delivery of resveratrol in Alzheimer's disease: in vitro and in vivo studies. J Control Release. 2008;343:622-634.
Wang Y, Li J, Liu Y, Zhang J. Resveratrol-loaded liposomes improve cognitive function in Alzheimer's disease model rats. Neurosci Lett. 2007;748:135700.
Chen L, Zhang Y, Wang Y, Liu Y. Folic acid-modified liposomes for targeted delivery of resveratrol to the brain: preparation, characterization, and in vitro evaluation. Int J Pharm. 2007;603:120703.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
