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Technological Advances in Improving Bioavailability of Phytochemicals for the Treatment of Alzheimer’s Disease

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Nutrients and Nutraceuticals for Active & Healthy Ageing

Abstract

Alzheimer’s disease (AD) is globally the most prevalent age-related neurodegenerative disease. There are drugs available for symptomatic treatment of the disease to delay the progression of symptoms of neurocognitive and physical decline. Studies have demonstrated many phytochemicals as candidates for the treatment of AD with anti-cholinesterase, anti-amyloidogenic, antioxidant, and anti-inflammatory effects. However, their properties differ from those of drugs. Many factors may play a critical role in limiting the bioavailability of these plant-originated chemicals. Therefore, studies have focused on developing new drug delivery systems like phytosomes, nanotechnology-based technologies, etc., to enable effective and reliable delivery of phytochemicals to the central nervous system (CNS). However, we still do not have any data on long-term treatment with phytochemicals delivered by these systems in AD.

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References

  • Aalinkeel R, Kutscher HL, Singh A, Cwiklinski K, Khechen N, Schwartz SA et al (2018) Neuroprotective effects of a biodegradable poly (lactic-co-glycolic acid)-ginsenoside Rg3 nanoformulation: a potential nanotherapy for Alzheimer’s disease? J Drug Target 26(2):182–193

    CAS  Google Scholar 

  • Agrawal M, Saraf S, Saraf S, Antimisiaris SG, Chougule MB, Shoyele SA et al (2018) Nose-to-brain drug delivery: an update on clinical challenges and progress towards approval of anti-Alzheimer drugs. J Control Release 281:139–177

    CAS  Google Scholar 

  • Akram M, Nawaz A (2017) Effects of medicinal plants on Alzheimer’s disease and memory deficits. Neural Regen Res 12(4):660

    Google Scholar 

  • Aminoff M, Greenberg D, Simon R (2015) Clinical neurology. McGraw-Hill Education, New York

    Google Scholar 

  • Amri A, Chaumeil J, Sfar S, Charrueau C (2012) Administration of resveratrol: what formulation solutions to bioavailability limitations? J Control Release 158(2):182–193

    CAS  Google Scholar 

  • Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4(6):807–818

    CAS  Google Scholar 

  • Aw-Yong PY, Gan PH, Sasmita AO, Mak ST, Ling A (2018) Nanoparticles as carriers of phytochemicals: recent applications against lung cancer. Int J Res Biomed Biotechnol 7:1–11

    Google Scholar 

  • Bicer N, Yildiz E, Yegani AA, Aksu F (2018) Synthesis of curcumin complexes with iron (iii) and manganese (ii), and effects of curcumin–iron (iii) on Alzheimer’s disease. New J Chem 42(10):8098–8104

    CAS  Google Scholar 

  • Charytoniuk T, Drygalski K, Konstantynowicz-Nowicka K, Berk K, Chabowski A (2017) Alternative treatment methods attenuate the development of NAFLD: a review of resveratrol molecular mechanisms and clinical trials. Nutrition 34:108–117

    CAS  Google Scholar 

  • Cheng G, Xu P, Zhang M, Chen J, Sheng R, Ma Y (2018) Resveratrol-maltol hybrids as multi-target-directed agents for Alzheimer’s disease. Bioorg Med Chem 26(22):5759–5765

    CAS  Google Scholar 

  • Desai PP, Patravale VB (2018) Curcumin cocrystal micelles—multifunctional nanocomposites for management of neurodegenerative ailments. J Pharm Sci 107(4):1143–1156

    CAS  Google Scholar 

  • Devi VK, Jain N, Valli KS (2010) Importance of novel drug delivery systems in herbal medicines. Pharmacogn Rev 4(7):27

    Google Scholar 

  • Drygalski K, Fereniec E, Koryciński K, Chomentowski A, Kiełczewska A, Odrzygóźdź C et al (2018) Resveratrol and Alzheimer’s disease. From molecular pathophysiology to clinical trials. Exp Gerontol 113:36

    CAS  Google Scholar 

  • Duttagupta AS, Chaudhary HM, Jadhav KR, Kadam VJ (2016) Cubosomes: innovative nanostructures for drug delivery. Curr Drug Deliv 13(4):482–493

    CAS  Google Scholar 

  • Elnaggar YS, Etman SM, Abdelmonsif DA, Abdallah OY (2015a) Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in Alzheimer’s disease: optimization, biological efficacy, and potential toxicity. J Pharm Sci 104(10):3544–3556

    CAS  Google Scholar 

  • Elnaggar YS, Etman SM, Abdelmonsif DA, Abdallah OY (2015b) Novel piperine-loaded Tween-integrated monoolein cubosomes as brain-targeted oral nanomedicine in Alzheimer’s disease: pharmaceutical, biological, and toxicological studies. Int J Nanomedicine 10:5459

    CAS  Google Scholar 

  • Etman SM, Elnaggar YS, Abdelmonsif DA, Abdallah OY (2018) Oral brain-targeted microemulsion for enhanced piperine delivery in Alzheimer’s disease therapy: in vitro appraisal, in vivo activity, and nanotoxicity. AAPS PharmSciTech 19(8):3698–3711

    CAS  Google Scholar 

  • Fan S, Zheng Y, Liu X, Fang W, Chen X, Liao W et al (2018) Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease. Drug Deliv 25(1):1091–1102

    CAS  Google Scholar 

  • Goodman LS (1996) Goodman and Gilman’s the pharmacological basis of therapeutics. McGraw-Hill, New York

    Google Scholar 

  • Gupta R, Xie H (2018) Nanoparticles in daily life: applications, toxicity and regulations. J Environ Pathol Toxicol Oncol 37(3):209

    Google Scholar 

  • Hamidi M, Azadi A, Rafiei P (2008) Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev 60(15):1638–1649

    CAS  Google Scholar 

  • Harvey AL, Clark RL, Mackay SP, Johnston BF (2010) Current strategies for drug discovery through natural products. Expert Opin Drug Discovery 5(6):559–568

    CAS  Google Scholar 

  • Huegel HM (2015) Brain food for Alzheimer-free ageing: focus on herbal medicines. In: Natural compounds as therapeutic agents for amyloidogenic diseases. Springer, Cham, pp 95–116

    Google Scholar 

  • Jadhav NR, Nadaf SJ, Lohar DA, Ghagare PS, Powar TA (2017) Phytochemicals formulated as nanoparticles: inventions, recent patents and future prospects. Recent Pat Drug Deliv Formul 11(3):173–186

    CAS  Google Scholar 

  • Jeřábek J, Uliassi E, Guidotti L, Korábečný J, Soukup O, Sepsova V et al (2017) Tacrine-resveratrol fused hybrids as multi-target-directed ligands against Alzheimer’s disease. Eur J Med Chem 127:250–262

    Google Scholar 

  • Kimura I (2006) Medical benefits of using natural compounds and their derivatives having multiple pharmacological actions. Yakugaku Zasshi 126(3):133–143

    CAS  Google Scholar 

  • Kochi A, Jin Lee H, Vithanarachchi SM, Padmini V, Allen JM, Hee Lim M (2015) Inhibitory activity of curcumin derivatives towards metal-free and metal-induced amyloid-β aggregation. Curr Alzheimer Res 12(5):415–423

    CAS  Google Scholar 

  • Kuo Y-C, Tsao C-W (2017) Neuroprotection against apoptosis of SK-N-MC cells using RMP-7-and lactoferrin-grafted liposomes carrying quercetin. Int J Nanomedicine 12:2857

    CAS  Google Scholar 

  • Liu H, Qu Y, Wang X (2018) Amyloid β-targeted metal complexes for potential applications in Alzheimer’s disease. Future Med Chem 10(6):679–701

    CAS  Google Scholar 

  • Liu Y, Zhou H, Yin T, Gong Y, Yuan G, Chen L et al (2019) Quercetin-modified gold-palladium nanoparticles as a potential autophagy inducer for the treatment of Alzheimer’s disease. J Colloid Interface Sci 552:388–400

    CAS  Google Scholar 

  • Loureiro J, Andrade S, Duarte A, Neves A, Queiroz J, Nunes C et al (2017) Resveratrol and grape extract-loaded solid lipid nanoparticles for the treatment of Alzheimer’s disease. Molecules 22(2):277

    Google Scholar 

  • Lu X, Ji C, Xu H, Li X, Ding H, Ye M et al (2009) Resveratrol-loaded polymeric micelles protect cells from Aβ-induced oxidative stress. Int J Pharm 375(1-2):89–96

    CAS  Google Scholar 

  • Ma T, Tan M-S, Yu J-T, Tan L (2014) Resveratrol as a therapeutic agent for Alzheimer’s disease. Biomed Res Int 2014:1

    Google Scholar 

  • Malekpour-Galogahi F, Hatamian-Zarmi A, Ganji F, Ebrahimi-Hosseinzadeh B, Nojoki F, Sahraeian R et al (2018) Preparation and optimization of rivastigmine-loaded tocopherol succinate-based solid lipid nanoparticles. J Liposome Res 28(3):226–235

    CAS  Google Scholar 

  • Mathew A, Fukuda T, Nagaoka Y, Hasumura T, Morimoto H, Yoshida Y et al (2012) Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. PLoS One 7(3):e32616

    CAS  Google Scholar 

  • Meng Q, Wang A, Hua H, Jiang Y, Wang Y, Mu H et al (2018) Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease. Int J Nanomedicine 13:705

    CAS  Google Scholar 

  • Misra S, Chopra K, Saikia UN, Sinha VR, Sehgal R, Modi M et al (2016) Effect of mesenchymal stem cells and galantamine nanoparticles in rat model of Alzheimer’s disease. Regen Med 11(7):629–646

    CAS  Google Scholar 

  • Mourtas S, Lazar AN, Markoutsa E, Duyckaerts C, Antimisiaris SG (2014) Multifunctional nanoliposomes with curcumin–lipid derivative and brain targeting functionality with potential applications for Alzheimer disease. Eur J Med Chem 80:175–183

    CAS  Google Scholar 

  • Mufamadi MS, Choonara YE, Kumar P, Modi G, Naidoo D, van Vuuren S et al (2013) Ligand-functionalized nanoliposomes for targeted delivery of galantamine. Int J Pharm 448(1):267–281

    CAS  Google Scholar 

  • Mutlu NB, Değim Z, Yılmaz Ş, Eşsiz D, Nacar A (2011) New perspective for the treatment of Alzheimer diseases: liposomal rivastigmine formulations. Drug Dev Ind Pharm 37(7):775–789

    CAS  Google Scholar 

  • Ovais M, Zia N, Ahmad I, Khalil AT, Raza A, Ayaz M et al (2018) Phyto-therapeutic and nanomedicinal approaches to cure Alzheimer’s disease: present status and future opportunities. Front Aging Neurosci 10:284

    CAS  Google Scholar 

  • Patel PA, Patil SC, Kalaria DR, Kalia YN, Patravale VB (2013) Comparative in vitro and in vivo evaluation of lipid based nanocarriers of Huperzine A. Int J Pharm 446(1-2):16–23

    CAS  Google Scholar 

  • Picciano AL, Vaden TD (2013) Complexation between Cu (II) and curcumin in the presence of two different segments of amyloid β. Biophys Chem 184:62–67

    CAS  Google Scholar 

  • Rai S, Pandey V, Rai G (2017) Transfersomes as versatile and flexible nano-vesicular carriers in skin cancer therapy: the state of the art. Nano Rev Exp 8(1):1325708

    Google Scholar 

  • Rajput A, Bariya A, Allam A, Othman S, Butani SB (2018) In situ nanostructured hydrogel of resveratrol for brain targeting: in vitro-in vivo characterization. Drug Deliv Transl Res 8(5):1460–1470

    CAS  Google Scholar 

  • Rishitha N, Muthuraman A (2018) Therapeutic evaluation of solid lipid nanoparticle of quercetin in pentylenetetrazole induced cognitive impairment of zebrafish. Life Sci 199:80–87

    CAS  Google Scholar 

  • Sadegh Malvajerd S, Izadi Z, Azadi A, Kurd M, Derakhshankhah H, Sharif Zadeh M et al (2019) Neuroprotective potential of curcumin-loaded nanostructured lipid carrier in an animal model of Alzheimer’s disease: behavioral and biochemical evidence. J Alzheimers Dis 69:671

    CAS  Google Scholar 

  • Salem HF, Kharshoum RM, Abou-Taleb HA, Naguib DM (2019) Brain targeting of resveratrol through intranasal lipid vesicles labelled with gold nanoparticles: in vivo evaluation and bioaccumulation investigation using computed tomography and histopathological examination. J Drug Target 27:1127–1134

    CAS  Google Scholar 

  • Shah BM, Misra M, Shishoo CJ, Padh H (2015) Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization. Drug Deliv 22(7):918–930

    CAS  Google Scholar 

  • Shakeri A, Sahebkar A (2016a) Opinion paper: phytosome: a fatty solution for efficient formulation of phytopharmaceuticals. Recent Pat Drug Deliv Formul 10(1):7–10

    CAS  Google Scholar 

  • Shakeri A, Sahebkar A (2016b) Opinion paper: nanotechnology: a successful approach to improve oral bioavailability of phytochemicals. Recent Pat Drug Deliv Formul 10(1):4–6

    CAS  Google Scholar 

  • Shakeri A, Panahi Y, Johnston TP, Sahebkar A (2019) Biological properties of metal complexes of curcumin. Biofactors 45(3):304–317

    CAS  Google Scholar 

  • Shoji Y, Nakashima H (2004) Nutraceutics and delivery systems. J Drug Target 12(6):385–391

    CAS  Google Scholar 

  • Singh N, Seedat F, Pillay V, Sweet JL, Danckwerts MP (2006) Formulation and statistical optimization of novel double-incorporated PLA-PLGA microparticles within an alginate-pectinate platform for the delivery of nicotine. J Microencapsul 23(2):153–167

    CAS  Google Scholar 

  • Singh Y, Meher JG, Raval K, Khan FA, Chaurasia M, Jain NK et al (2017) Nanoemulsion: concepts, development and applications in drug delivery. J Control Release 252:28–49

    CAS  Google Scholar 

  • Sood S, Jain K, Gowthamarajan K (2014) Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloids Surf B: Biointerfaces 113:330–337

    CAS  Google Scholar 

  • Squillaro T, Cimini A, Peluso G, Giordano A, Melone MAB (2018) Nano-delivery systems for encapsulation of dietary polyphenols: an experimental approach for neurodegenerative diseases and brain tumors. Biochem Pharmacol 154:303–317

    CAS  Google Scholar 

  • Subbiah R, Veerapandian M, Yun KS (2010) Nanoparticles: functionalization and multifunctional applications in biomedical sciences. Curr Med Chem 17(36):4559–4577

    CAS  Google Scholar 

  • Sun D, Li N, Zhang W, Zhao Z, Mou Z, Huang D et al (2016) Design of PLGA-functionalized quercetin nanoparticles for potential use in Alzheimer’s disease. Colloids Surf B: Biointerfaces 148:116–129

    CAS  Google Scholar 

  • Tayeb HH, Sainsbury F (2018) Nanoemulsions in drug delivery: formulation to medical application. Nanomedicine 13(19):2507–2525

    CAS  Google Scholar 

  • Tsao R (2010) Chemistry and biochemistry of dietary polyphenols. Nutrients 2(12):1231–1246

    CAS  Google Scholar 

  • Uddin MS, Al Mamun A, Kabir MT, Jakaria M, Mathew B, Barreto GE et al (2019) Nootropic and anti-Alzheimer’s actions of medicinal plants: molecular insight into therapeutic potential to alleviate Alzheimer’s neuropathology. Mol Neurobiol 56(7):4925–4944

    CAS  Google Scholar 

  • Van der Schyf CJ, Geldenhuys WJ, Youdim MB (2006) Multifunctional drugs with different CNS targets for neuropsychiatric disorders. J Neurochem 99(4):1033–1048

    Google Scholar 

  • Wahba SM, Darwish AS, Kamal SM (2016) Ceria-containing uncoated and coated hydroxyapatite-based galantamine nanocomposites for formidable treatment of Alzheimer’s disease in ovariectomized albino-rat model. Mater Sci Eng C 65:151–163

    CAS  Google Scholar 

  • Wang T, Wu C, Fan G, Li T, Gong H, Cao F (2018) Ginkgo biloba extracts-loaded starch nano-spheres: preparation, characterization, and in vitro release kinetics. Int J Biol Macromol 106:148–157

    CAS  Google Scholar 

  • Wilson B, Samanta MK, Muthu MS, Vinothapooshan G (2011) Design and evaluation of chitosan nanoparticles as novel drug carrier for the delivery of rivastigmine to treat Alzheimer’s disease. Ther Deliv 2(5):599–609

    CAS  Google Scholar 

  • Woo FY, Basri M, Masoumi HRF, Ahmad MB, Ismail M (2015) Formulation optimization of galantamine hydrobromide loaded gel drug reservoirs in transdermal patch for Alzheimer’s disease. Int J Nanomedicine 10:3879

    CAS  Google Scholar 

  • Yang CS, Sang S, Lambert JD, Lee MJ (2008) Bioavailability issues in studying the health effects of plant polyphenolic compounds. Mol Nutr Food Res 52(S1):S139–SS51

    Google Scholar 

  • Yang X, Qiang X, Li Y, Luo L, Xu R, Zheng Y et al (2017) Pyridoxine-resveratrol hybrids Mannich base derivatives as novel dual inhibitors of AChE and MAO-B with antioxidant and metal-chelating properties for the treatment of Alzheimer’s disease. Bioorg Chem 71:305–314

    CAS  Google Scholar 

  • Yao EC, Xue L (2014) Therapeutic effects of curcumin on Alzheimer’s disease. Adv Alzheimers Dis 3(04):145

    Google Scholar 

  • Yusuf M, Khan M, Khan RA, Ahmed B (2013) Preparation, characterization, in vivo and biochemical evaluation of brain targeted Piperine solid lipid nanoparticles in an experimentally induced Alzheimer’s disease model. J Drug Target 21(3):300–311

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Pharmacology, Faculty of Medicine, University of Sanko, Gaziantep, Turkey

    Mehtap Ozkur & Necla Benlier

  2. Department of Medical Biochemistry, Faculty of Medicine, University of Sanko, Gaziantep, Turkey

    Ilker Saygili & Eda Ogut

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  1. Mehtap Ozkur
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  2. Necla Benlier
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  3. Ilker Saygili
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  4. Eda Ogut
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Correspondence to Mehtap Ozkur .

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Editors and Affiliations

  1. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Seyed Mohammad Nabavi

  2. Clinical Psychology Service, Clinical Psychology Service, Health Department, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy

    Grazia D'Onofrio

  3. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Seyed Fazel Nabavi

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Ozkur, M., Benlier, N., Saygili, I., Ogut, E. (2020). Technological Advances in Improving Bioavailability of Phytochemicals for the Treatment of Alzheimer’s Disease. In: Nabavi, S.M., D'Onofrio, G., Nabavi, S.F. (eds) Nutrients and Nutraceuticals for Active & Healthy Ageing. Springer, Singapore. https://doi.org/10.1007/978-981-15-3552-9_12

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