ANTI-OBESITY NUTRACEUTICALS: INSIGHTS INTO MECHANISMS OF ACTION AND POTENTIAL USE OF BIOCOMPATIBLE NANOCARRIERS FOR DELIVERY

DOAA SALAH ELDIN ABDELFATTAH; MERVAT A. FOUAD; ALIAA N. ELMESHAD; MOHAMED A. El-NABARAWI; SAMMAR FATHY ELHABAL

doi:10.22159/ijap.2024v16i4.50773

Authors

DOAA SALAH ELDIN ABDELFATTAH National Nutrition Institute, Cairo-11435, Egypt. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Giza-11562, Egypt https://orcid.org/0000-0001-8449-2556
MERVAT A. FOUAD National Nutrition Institute, Cairo-11435, Egypt
ALIAA N. ELMESHAD Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Giza-11562, Egypt. Department of Pharmaceutics, Faculty of Pharmacy and Drug Technology, The Egyptian Chinese University, Cairo-11786, Egypt https://orcid.org/0000-0002-9454-7458
MOHAMED A. El-NABARAWI Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Giza-11562, Egypt https://orcid.org/0000-0003-0070-1969
SAMMAR FATHY ELHABAL Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo-11571, Egypt

DOI:

https://doi.org/10.22159/ijap.2024v16i4.50773

Keywords:

Obesity, Nutraceutical, WKBE, PEE, CrPic3, Biocompatible carriers, Drug delivery system

Abstract

One of the serious health issues that has detrimental effects on health is obesity. Obesity is associated with common comorbidities like, diabetes, dyslipidemia, and cardiovascular diseases. New understanding of the pathophysiologic mechanisms underlying obesity has led to the development of several novel agents and effective strategies to combat the global obesity epidemic and its comorbidities. The objective of managing obesity has changed to include both reducing its complications and helping people lose weight.Although there are more pharmaceutical options available for managing obesity, their efficacy and safety profiles are either limited or moderate. While behavior interventions and active lifestyle remain the cornerstones of successful weight loss, it can be very challenging to maintain such a healthy lifestyle. Thus, new agents that are safer and more effective are therefore urgently needed. Natural products and dietary supplements have been demonstrated as a potential treatment for obesity. Recent studies suggested that propolis, chromium picolinate, and White Kidney Bean Extract (WKBE) may have anti-obesity properties. This review provides an overview on the anti-obesity effects of these natural products, their active ingredients and mechanisms of action. In addition to potential cutting-edge delivery techniques that can be applied to maximize the anti-obesity effects of these bioactive substances with varying solubility, bioavailability, and stability.

Downloads

Download data is not yet available.

References

Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism. 2019;92:6-10.

BlüherM.Obesity:global epidemiology and pathogenesis. Nature Reviews Endocrinology. 2019;15:288–298.

Neil ES, McGinley JN, Fitzgerald VK, Lauck CA, Tabke JA, Streeter-McDonald MR, Yao L, Broeckling CD, Weir TL, Foster MT, Thompson HJ. White Kidney Bean (Phaseolus Vulgaris L.) Consumption Reduces Fat Accumulation in a Polygenic Mouse Model of Obesity. Nutrients. 2019;11:2780.

Thompson HJ, McGinley JN, Neil ES, Brick MA. Beneficial Effects of Common Bean on Adiposity and Lipid Metabolism. Nutrients. 2017;9:998.

ShiZ, ZhuY, Teng C, YaoY, RenG, RichelA. Anti-obesity effects of α-amylase inhibitor enriched-extract from white common beans (Phaseolus vulgaris L.) associated with the modulation of gut microbiota composition in high-fat diet-induced obese rats. Food Funct. 2020;11:1624–1634.

Pasupuleti VR, Sammugam L, Ramesh N, Gan SH. Honey. Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits. Oxid Med Cell Longev. 2017;2017:1259510.

AnjumSI, UllahA, KhanKA, AttaullahM, KhanH, AliH, BashirMA, TahirM, AnsariMJ, GhramhHA, Adgaba N, Dash CK. Composition and functional properties of propolis (bee glue): A review. Saudi J. Biol. Sci. 2019;26:1695-1703.

Albarracin CA, Fuqua BC, Evans JL, Goldfine ID. Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes. Diabetes Metab Res Rev. 2008;24:41-51

Docherty JP, Sack DA, Roffman M, Finch M, Komorowski JR. A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving. J PsychiatrPract. 2005;11:302-314.

Abdelfattah DSE, Fouad MA, Elmeshad AN, El-Nabarawi MA, Elhabal SF. Anti-Obesity Effect of Combining White Kidney Bean Extract, Propolis Ethanolic Extract and CrPi3 on Sprague-Dawley Rats Fed a High-Fat Diet. Nutrients. 2024; 16:310.

Ebrahimi B, Baroutian S, Li J, Zhang B, Ying T, Lu J. Combination of marine bioactive compounds and extracts for the prevention and treatment of chronic diseases. Front Nutr. 2023;9:1047026.

Panahi Y, Hosseini MS, Khalili N, Naimi E, Majeed M, Sahebkar A. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clin Nutr. 2015;34:1101-1108.

Manocha S,Dhiman S,Singh AG,Guarve K. Nanotechnology: An approach to overcome bioavailability challenges of nutraceuticals,. Journal of Drug Delivery Science and Technology. 2022; 72:103418.

World Health Organization [Internet]. Obesity and Overweight; [cited 2023 Dec]. Available from: https://www.who.int/en/news-room/factsheets/detail/obesity-and-overweight

Aboulghate M, Elaghoury A, ElebrashyI,Elkafrawy N, Elshishiney G, Abul-Magd E, Bassiouny E, Toaima D, Elezbawy B, Fasseeh A, Abaza S, Vokó Z. The Burden of Obesity in Egypt. Front Public Health. 2021;9:718978.

SainiJ, Lora SS, Gupta MC. Maternal obesity as a predictive marker for adverse pregnancy outcome: A case-control study. Asian J Pharm Clin Res. 2023;16:33-37.

Taroeno-Hariadi KW, Hardianti MS, Sinorita H, Aryandono T. Obesity, leptin, and deregulation of microRNA in lipid metabolisms: their contribution to breast cancer prognosis. DiabetolMetabSyndr. 2021;13:10.

Mohammad S, Aziz R, Al Mahri S, Malik SS, Haji E, Khan AH,Khatlani TS,BouchamaA. Obesity and COVID-19: What makes obese host so vulnerable? Immun. Ageing. 2021;18:1.

Hu S, Wang L, Yang D, Li L, Togo J, Wu Y, Liu Q, Li B, Li M, Wang G, Zhang X, Niu C, Li J, Xu Y, Couper E, Whittington-Davies A, Mazidi M, Luo L, Wang S, Douglas A, Speakman JR. Dietary Fat, but Not Protein or Carbohydrate, Regulates Energy Intake and Causes Adiposity in Mice. Cell Metab. 2018;28:415-431.

Gariani K, Ryu D, Menzies KJ, Yi HS, Stein S, Zhang H, Perino A, Lemos V, Katsyuba E, Jha P, Vijgen S, Rubbia-Brandt L, Kim YK, Kim JT, Kim KS, Shong M, Schoonjans K, Auwerx J. Inhibiting poly ADP-ribosylation increases fatty acid oxidation and protects against fatty liver disease. J Hepatol. 2017;66:132-141.

Kotsis V, AntzaC, DoundoulakisG, StabouliS.Obesity, Hypertension, and Dyslipidemia. Springer,US;2019.

KulmiM, Saxena G. Comparison of effects of Sitagliptin and a combination of naltrexone and bupropion in high fat-diet induced obesity model in rats. Asian J Pharm Clin Res.2022;15:119-23,

Apovian CM, Aronne LJ, Bessesen DH,McDonnell M, MuradMH, Pagotto U, Ryan D, Still DC. Pharmacological management of obesity: an endocrine Society clinical practice guideline.J Clin Endocrinol Metab. 2015;100:342-362.

Jakab J, Miškić B, Mikšić Š,Juranić B, Ćosić V, Schwarz D, Včev A. Adipogenesis as a Potential Anti-Obesity Target: A Review of Pharmacological Treatment and Natural Products. Diabetes MetabSyndrObes. 2021;14:67-83.

Dietary Supplements Market-Driven by Increasing Demand for Health Products: Global Industry Analysis and Opportunity Assessment 2015–2025; [cited 2023 Aug]. Available from: https://www.futuremarketinsights.com/reports/dietary-supplements-market.

Cragg GM, Pezzuto JM. Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents. Med PrincPract. 2016;25:41-59.

Peddio S, Padiglia A, Cannea FB,Crnjar R, Zam W, Sharifi-Rad J, Rescigno A, Zucca P. Common bean (Phaseolus vulgarisL.) α-amylase inhibitors as safe nutraceutical strategy against diabetes and obesity: An update review. Phytother Res. 2022;36(7):2803-2823.

Los F, Zielinski A,Wojeicchowski JP, Nogueira A, Demiate IM. Beans (Phaseolus vulgaris L.): whole seeds with complex chemical composition. Current Opinion in Food Science. 2018;19:63–71.

PopAV, CiulcaS. Phenotypic variability of pod traits in dry bean genotypes from Romania. Journal of Horticulture, Forestry and Biotechnology. 2013;17:380-385.

Rebello CJ, Greenway FL, Finley JW. A review of the nutritional value of legumes and their effects on obesity and its related co-morbidities. Obes Rev. 2014;15:392-407.

Du W, Jia X, Jiang H, Wang, Y, Li L, Zhang B. Consumption of dried legume and legume products among adults aged 18–59 years old in 15 provinces in China in 2015. Acta NutrimentaSinica. 2018;40:17–22.

Yao Y, Hu Y, Zhu Y, Gao Y, Ren G. Comparisons of phaseolin type and α-amylase inhibitor in common bean (Phaseolus vulgaris L.) in China. 8e Crop Journal. 2016;4:68-72.

Nciri N, Cho N. New research highlights: Impact of chronic ingestion of white kidney beans (Phaseolus vulgaris L. var. Beldia) on small-intestinal disaccharidase activity in Wistar rats. Toxicol Rep. 2017;5:46-55.

Thompson HJ, McGinley JN, Neil ES, Brick MA. Beneficial Effects of Common Bean on Adiposity and Lipid Metabolism. Nutrients 2017;9:998.

LüthiC. Álvarez‐Alfageme F, LiY, NaranjoSE, HigginsTJV,Romeis J. Potential of the bean α‐amylase inhibitor α AI‐1 to inhibit α‐amylase activity in true bugs (Hemiptera). Journal of Applied Entomology. 2015;139:192-200.

Yang CH, Chiang MT. Effects of white kidney bean extracts on carbohydrate and lipid metabolism in rats fed a high fat diet. Taiwanese Journal of Agricultural Chemistry and Food Science 2014;52:154-162

Thom E. A randomized, double-blind, placebo-controlled trial of a new weight-reducing agent of natural origin. J Int Med Res 2000;28:229-233.

Boivin M, Zinsmeister AR, Go VL, DiMagno EP. Effect of a purified amylase inhibitor on carbohydrate metabolism after a mixed meal in healthy humans. Mayo Clin Proc. 1987;62:249-255.

Boivin M, Flourie B, Rizza RA, Go VL, DiMagno EP. Gastrointestinal and metabolic effects of amylase inhibition in diabetics. Gastroenterology. 1988;94:387-394.

Harikumar KB, Jesil AM, Sabu MC, Kuttan R. A preliminary assessment of the acute and subchronic toxicity profile of phase2: an alpha-amylase inhibitor. Int J Toxicol. 2005;24:95-102.

Abdelrazeg S, Hussin H, Salih M. Propolis composition and applications in medicine and health. Int Med J. 2020;25:1505-42.

Sforcin JM. Biological Properties and Therapeutic Applications of Propolis. Phytother Res. 2016;30:894-905.

Hori JI, Zamboni DS, Carrão DB, Goldman GH, Berretta AA. The Inhibition of inflammasome by Brazilian Propolis (EPP-AF). Evidence-Based Complementary and Alternative Medicine. 2013;2013:418508.

Nascimento AP, Ferreira NU, Barizon EA, Rocha BA, Vaz MMOLL, Berretta AA. Methodologies for the evaluation of the antibacterial activity of propolis. African Journal of Microbiology Research. 2013;7:2344-2350.

Rocha BA, Bueno PC, Vaz MM, Nascimento AP, Ferreira NU, Moreno Gde P, Rodrigues MR, Costa-Machado AR, Barizon EA, Campos JC, de Oliveira PF, AcésioNde O, Martins Sde P, Tavares DC, Berretta AA. Evaluation of a Propolis Water Extract Using a Reliable RP-HPLC Methodology and In Vitro and In Vivo Efficacy and Safety Characterisation. Evid Based Complement Alternat Med. 2013;2013:670451.

Tsuda T, Kumazawa S. Propolis: Chemical Constituents, Plant Origin, and Possible Role in the Prevention and Treatment of Obesity and Diabetes. J Agric Food Chem. 2021;69:15484-494.

Bankova V, Popova M, Trusheva B. The phytochemistry of the honeybee. Phytochemistry. 2018;155:1-11.

Abdl El HadyFK, HegaziAG.Gas chromatography– mass spectrometry (GC/MS) study of the Egyptian propolis 1- aliphatic, phenolic acids and their esters. Journal of Applied Sciences. 1994;9:749-760.

Balica G, Vostinaru O, Stefanescu C, Mogosan C, Iaru I, Cristina A, Pop CE. Potential role of Propolis in the prevention and treatment of metabolic diseases. PLANTS-BASEL. 2021;10:883.

Natsir R, Usman AN, Ardyansyah BD, Fendi F. Propolis and honey trigona decrease leptin levels of central obesity patients. Enferm Clin. 2020;30:96–9.

ChenLH,Chien YW, Chang ML, HouCC, ChanCH, TangHW, HuangHY. Taiwanese Green Propolis Ethanol Extract Delays the Progression of Type 2 Diabetes Mellitus in Rats Treated with Streptozotocin/High-Fat Diet. Nutrients. 2018;10:503.

Han X, Guo J, You Y, Zhan J, Huang W. P-Coumaric acid prevents obesity via activating thermogenesis in brown adipose tissue mediated by mTORC1-RPS6. FASEB J. 2020;34:7810-24.

Boisard S, Le Ray AM, Gatto J, Aumond MC, Blanchard P, Derbré S, Flurin C, Richomme P. Chemical composition, antioxidant and anti-AGEs activities of a French poplar type Propolis. J Agric Food Chem. 2014;62:1344-51.

Nie J, Chang Y, Li Y, Zhou Y, Qin J, Sun Z, Li H. Caffeic acid Phenethyl Ester (Propolis extract) ameliorates insulin resistance by inhibiting JNK and NF-κB inflammatory pathways in diabetic mice and HepG2 cell models. J Agric Food Chem. 2017;65:9041-53.

Shin SH, Seo SG, Min S, Yang H, Lee E, Son JE, Kwon JY, Yue S, Chung MY, Kim KH, Cheng JX, Lee HJ, Lee KW. Caffeic acid Phenethyl Ester, major component of Propolis, suppresses high fat diet-induced obesity through inhibiting Adipogenesis at the mitotic clonal expansion stage. J Agric Food Chem. 2014;62:4306-12.

Xu J, Ge J, He X, Sheng Y, Zheng S, Zhang C, Xu W, HuangK. Caffeic acid reduces body weight by regulating gut microbiota in diet-induced-obese mice. J Funct Foods. 2020;74:104061.

Liao CC, Ou TT, Wu CH, Wang CJ. Prevention of diet-induced hyperlipidemia and obesity by Caffeic acid in C57BL/6 mice through regulation of hepatic lipogenesis gene expression. J Agric Food Chem. 2013;61:11082-8.

Cardinault N, Tourniaire F, Astier J, Couturier C, Bonnet L, Seipelt E, Karkeni E, Letullier C, Dlalah N, Georgé S, Mounien L, Landrier JF. Botanic origin of Propolis extract powder drives contrasted impact on Diabesity in high-fat-fed mice. Antioxidants. 2021;10:411.

Fei N, ZhaoL.An opportunistic pathogen isolated from the gut of an obese human causes obesity in germ-free mice. ISME Journal. 2013;7:880–884.

Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, FalonyG,Pedersen O.Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500:541–546.

Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA,Pedersen O.Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016;535:376–381.

Tremaroli V,Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489:242-249.

Roquetto AR, Santana Monteiro NE, Moura CS, Toreti VC, de Pace F, dos Santos A, Park YK, Amaya-Farfan J. Green propolis modulates gut microbiota, reduces endotoxemia and expression of TLR4 pathway in mice fed a high-fat diet. Food Res Int. 2015;76:796–803.

Cai W, Xu J, Li G, Liu T, Guo X, Wang H, Luo L. Ethanol extract of propolis prevents high-fat diet-induced insulin resistance and obesity in association with modulation of gut microbiota in mice. Food Res Int. 2020;130:108939.

Drake TC, Rudser KD, Seaquist ER, Saeed A. Chromium infusion in hospitalised patients with severe insulin resistance: a retrospective analysis. Endodontic Practice. 2012;31:1-17.

Kaats GR, Blum K, Fisher JA, Adelman JA. Effects of chromium Picolinate supplementation on body composition: a randomized, double-masked, placebo-controlled study. CurrTher Res. 1996;57: 747-756.

Joseph LJO, Farrell PA, Davey SL, Evans WJ, Campbell WW. Effect ofresistance training with or without chromium picolinate supplementationon glucose metabolism in older men and women. Metabolism. 1999;48:546-553.

Aghdassi E, Arendt BM, Salit IE, Mohammed SS, Jalali P, Bondar H, Allard JP. In patients with HIV-infection,chromium supplementation improves insulin resistance and othermetabolic abnormalities: a randomized, double-blind, placebo controlledtrial. Curr HIV Res. 2010;8:113-120.

Robati P, Mozafari H, Najarzadeh A, Dehghan A, Khorami E. Theeffect of chromium Picolinate supplementation on body weight, body mass index and waist circumference inoverweight and obese people. Med J Mashhad. 2015;58:117-122.

Jo H, Wahl A. The effect of a new dietary mineral product on body composition and weight in overweight and obese people. The results from a comparative randomized 30-days study. J Obes Eat Disord. 2016;2:496-507.

Vincent J. Is the Pharmacological Mode of Action of Chromium (III) as a secondary messenger? Biological Trace Element Research. 2015;166:7-12.

Wang ZQ, Qin J, Martin J, Zhang XH, Sereda O, Anderson RA,Pinsonat P, Cefalu WT. Phenotype of subjects with type 2 diabetes mellitus may determine clinical response to chromium supplementation. Metabolism. 2007;56:1652-5.

Kalra EK. Nutraceutical-Definition and introduction. AAPS Pharm Sci. 2003;5:E25

Nasri H, Baradaran A, Shirzad H, Rafieian-Kopaei M. New concepts in nutraceuticals as alternative for pharmaceuticals. Int J Prev Med. 2014;5:1487-99.

McClements DJ, Zou L, Zhang R, Salvia-Trujillo L, Kumosani T, Xiao H. Enhancing nutraceutical performance using excipient foods: Designing food structures and compositions to increase bioavailability. Compr. Rev. Food Sci Food Saf. 2015;14:824-847

Asghar A, Randhawa MA, Masood MM, Abdullah M, Irshad MA. Nutraceutical formulation strategies to enhance the bioavailability and efficiency: An overview. Role of Materials Science in Food Bioengineering. Elsevier, US; 2018. p.329-352.

McClementsDJ,ÖztürkB.Utilizationofnanotechnologytoimprovethehandling,storageandbiocompatibilityofbioactivelipidsinfoodapplications.Foods. 2021;10:1-17

Jones D, Caballero S, Davidov-Pardo G. Bioavailability of nanotechnology-based bioactives and nutraceuticals. Adv Food Nutr Res. 2019;88:235-273.

PateiroM,GómezB,MunekataPES,BarbaFJ,PutnikP,KovačevićDB,LorenzoJM. Nanoencapsulationofpromisingbioactivecompoundstoimprovetheirabsorption, stability, functionalityandtheappearanceofthefinal foodproducts.Molecules. 2021;26:1547.

RehmanA,AhmadT,AadilRM,SpottiMJ,BakryAM,KhanIM,ZhaoL,RiazT,TongQ.Pectinpolymersaswallmaterialsforthenano-encapsulationofbioactivecompounds. Trends inFoodScienceandTechnology. 2019;90:35–46.

Jain A, Ranjan S, Dasgupta N, Ramalingam C. Nanomaterials in food and agriculture: An overview on their safety concerns and regulatory issues. Crit Rev Food Sci Nutr. 2018; 58: 297-317.

Higashisaka K, Nagano K, Yoshioka Y, Tsutsumi Y. Nano-safety research: Examining the associations among the biological effects of nanoparticles and their physicochemical properties and kinetics. Biol Pharm Bull. 2017;40: 243-8.

Zhang H, Jiang X, Cao G, Zhang X, Croley TR, Wu X, Yin JJ. Effects of noble metal nanoparticles on the hydroxyl radical scavenging ability of dietary antioxidants. J Environ Sci Health C Environ CarcinogEcotoxicol Rev. 2018;36: 84-97.

Zanella M, Ciappellano SG, Venturini M, Tedesco E, Manodori L, Benetti F. Nutraceuticals and nanotechnology. Diet Ing Supp. 2015;26:26-31.

Xiao J, Cao Y, Huang Q. Edible Nanoencapsulation Vehicles for Oral Delivery of Phytochemicals: A Perspective Paper. J. Agric Food Chem. 2017;65:6727-6735.

Fathi M., MartínA, McClements DJ. Nanoencapsulation of food ingredients using carbohydrate based delivery systems. Trends Food SciTechnol. 2014;39:18-39.

Samaranayaka AG, Li-Chan EC. Food-derived peptidic antioxidants: A review of their production, assessment, and potential applications. JFunct Foods. 2011;3:229-254.

Zhang R, Han Y,Xie W, Liu F, Chen S. Advances in Protein-Based Nanocarriers of Bioactive Compounds: From Microscopic Molecular Principles to Macroscopical Structural and Functional Attributes. J Agric Food Chem. 2022;70:6354-6367.

Fathi M,Donsi F, McClements DJ. Protein-Based Delivery Systems for the Nanoencapsulation of Food Ingredients. Compr Rev Food Sci Food Saf. 2018;17:920-936.

Wan ZL, Guo J, Yang XQ. Plant protein-based delivery systems for bioactive ingredients in foods. Food Funct. 2015;6:2876-2889.

Assadpour E, Jafari SM. An overview of specialized equipment for nanoencapsulation of food ingredients. In Nanoencapsulation of Food Ingredients by Specialized Equipment. Academic Press: Cambridge, MA, USA;2019. p.1-30.

Ahmed EM. Hydrogel: Preparation, characterization, and applications: A review. J Adv Res. 2015;6:105-21.

AhmadU, AliA, Khan MM, Siddiqui MA, Akhtar J, Ahmad FJ. Nanotechnology-Based Strategies for Nutraceuticals: A Review of Current Research Development. Nanosci Technol Int J. 2019;10:133–155.

Bhattacharya S, PAUL B,Biswas GR. Development and evaluation of hydrogel of an anti-fungal drug. International Journal of Pharmacy and Pharmaceutical Sciences. 2023;15:29-33

Singh D. Application of novel drug delivery system in enhancing the therapeutic potential of phytoconstituents. Asian J Pharm. 2015;9:4.

Saraf S. Applications of novel drug delivery system for herbal formulations. Fitoterapia. 2010;81:680-689.

Akhavan S,Assadpour E,Katouzian I, Jafari SM. Lipid Nano Scale Cargos for The Protection and Delivery of Food Bioactive Ingredients and Nutraceuticals. Trends Food Sci Technol. 2018;74:132-146.

MozafariMR, Flanagan, J,Matia-Merino L,Awati A,Omri A,Suntres ZE, Singh H. Recent trends in the lipid-based nanoencapsulation of antioxidants and their role in foods. JSci Food Agric. 2006;86:2038-2045

Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomed.2015;10:975-99.

Alshawwa SZ, Kassem AA, Farid RM, Mostafa SK, Labib GS. Nanocarrier Drug Delivery Systems: Characterization, Limitations, Future Perspectives and Implementation of Artificial Intelligence. Pharmaceutics. 2022;14:883.