International Journal of Drug Delivery Technology
Volume 14, Issue 1

In-vitro Analysis of Antioxidant, Anti-inflammatory, Antidiabetic and Antimicrobial Studies of Kaempferol Ethosomes

Raghav S Shraddha1, Bhavna Kumar1*, Sethiya K Neeraj1, Singhal Manmohan1, Arya Swati2

1Faculty of Pharmacy DIT University, Dehradun, Uttarakhand, India.

2SGT College of Pharmacy, Shree Guru Gobind Singh Tricentenary University, Gurugram, Haryana, India. 

Received: 10th September, 2023; Revised: 01st January, 2024; Accepted: 07th February, 2024; Available Online: 25th March, 2024

ABSTRACT

Flavonoids have potent antioxidant, anti-inflammatory, antidiabetic and antimicrobial properties, and they generally report to have poor bioavailability and dissolution. This work emphasized on developing and characterizing kaempferol-loaded ethosomes and evaluating them for in-vitro assessments. The cold method was used for preparing kaempferol (KMP) ethosomes by means of soya lecithin, ethanol, and propylene glycol. The ethosomes were evaluated for vesicle size (253 ± 2.6), entrapment efficiency (91.05 ± 0.11%), zeta potential (-31.7 ± 1.12 mV), and drug release (89.91 ± 3.3%), compared with the release of pure drug (kaempferol), which was 48.96 ± 3.6% and showed an approximate double increment in the release rate. KMP ethosomes follow the Korsmeyer-Peppas model. The kaempferol ethosomes were further examined for their various in-vitro pharmacological activities as antimicrobial, anti-inflammatory, antidiabetic, and antioxidant in comparison with pure kaempferol. The results reported kaempferol loaded-ethosomes showed a strong anti-inflammatory, antimicrobial, antioxidant, and antidiabetic properties and thus, can be exploited as a viable drug delivery for various therapeutic applications.

Keywords: Antidiabetic, Anti-inflammatory, Antimicrobial, Antioxidant, Ethosomes, Kaempferol. International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.1.17

How to cite this article: Shraddha RS, Kumar B, Neeraj SK, Manmohan S, Swati A. In-vitro Analysis of Antioxidant, Anti- Inflammatory, Antidiabetic and Antimicrobial Studies of Kaempferol Ethosomes. International Journal of Drug Delivery Technology. 2024;14(1):118-125.

REFERENCES

  1. Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis. Annals of medicine. 2017; 49(2):106-16. DOI:10.1080/07853890.2016.1231932
  2. Barjesteh T, Mansur S, Bao Y. Inorganic nanoparticle-loaded exosomes for biomedical applications. Molecules. 2021; 26(4):1135. DOI:10.3390/molecules26041135.
  3. Grip J, Steene E, Engstad RE, Hart J, Bell A, Skjæveland I, Basnet P, Škalko-Basnet N, Holsæter AM. Development of a novel beta-glucan supplemented hydrogel spray formulation and wound healing efficacy in a db/db diabetic mouse model. European Journal of Pharmaceutics and Biopharmaceutics. 2021;169:280-91. DOI:10.1016/j.ejpb.2021.10.013
  4. Özay Y, Güzel S, Yumrutaş Ö, Pehlivanoğlu B, Erdoğdu İH, Yildirim Z, Türk BA, Darcan S. Wound healing effect of kaempferol in diabetic and nondiabetic rats. Journal of Surgical Research. 2019; 233:284-96. DOI:10.1016/j.jss.2018.08.009
  5. Chen AY, Chen A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food chemistry. 2013;138(4):2099-107. DOI:10.1016/j.foodchem.2012.11.139
  6. Ashrafizadeh M, Tavakol S, Ahmadi Z, Roomiani S, Mohammadinejad R, Samarghandian Therapeutic effects of kaempferol affecting autophagy and endoplasmic reticulum stress. Phytotherapy research. 2020; 34(5):911-23. DOI: 10.1002/ ptr.6577.
  7. Raghav SS, Kumar B, Sethiya NK, Kaul A Mechanistic Insight on Phytoconstituents Delivering Hypoglycemic Activity: A Comprehensive Overview. Future Pharmacology. 2022;2(4):511-DOI:10.3390/futurepharmacol2040032
  8. M Calderon-Montano J, Burgos-Morón E, Pérez-Guerrero C, López-Lázaro A review on the dietary flavonoid kaempferol. Mini reviews in medicinal chemistry. 2011;11(4):298-344. DOI:1 0.2174/138955711795305335.
  9. Dabeek WM, Marra MV. Dietary quercetin and kaempferol: Bioavailability and potential cardiovascular-related bioactivity in Nutrients. 2019; 11(10):2288. DOI: 10.3390/nu11102288.
  10. Mohammed BS, Al Gawhari FJ. Transethosomes a novel transdermal drug delivery system for antifungal drugs. International Journal of Drug Delivery Technology. 2021; 11(1):238-243.
  11. Touitou E, Dayan N, Bergelson L, Godin B, Eliaz Ethosomes— novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. Journal of controlled release. 2000; 65(3):403-18. DOI: 10.1016/s0168-3659(99)00222-9.
  12. Touitou E, Godin B, Dayan N, Weiss C, Piliponsky A, Levi- Schaffer F. Intracellular delivery mediated by an ethosomal carrier. Biomaterials.2001; 22(22):3053-9.DOI:10.1016/s0142- 9612 (01)00052-7.
  13. Bhalaria, M, Naik S, Misra AN. Ethosome – a novel delivery system of antifungal drugs in treatment of topical fungal Indian Journal of Experimental Biology 2009; 47(5):368-75
  14. Muslim RK, Maraie Perspective Impact of Gelling Agents on the Mechanistic Behavior for the Topical Delivery of Flufenamic Acid Nano-Ethosomal Dispersion. International Journal of Drug Delivery Technology. 2022; 12(2):789-797.
  15. Singh A, Rathore P, Shukla M, Nayak S. Comparative studies on skin permeation of miconazole using different novel International Journal of Pharmaceutical Sciences and Research. 2010;1(9):61-6. DOI: 10.13040/IJPSR.0975-8232.1(9-S).61-66.
  16. El-Shenawy AA, Abdelhafez WA, Ismail A, Kassem AA. Formulation and characterization of nanosized ethosomal formulations of antigout model drug (febuxostat) prepared by cold method: In vitro/ex vivo and in vivo Aaps Pharmscitech. 2020; 21:1-3. DOI: 10.1208/s12249-019-1556-z.
  17. Chandran SC, Shirwaikar A, Kuriakose MR, Sabna NS. Development and evaluation of ethosomes for transdermal deliveryof Fluconazole. Journal of Chemical, Biological and Physical Sciences. (JCBPS) 2011; 2(1):254.
  18. Dara T, Vatanara A, Meybodi MN, Vakilinezhad MA, Malvajerd SS, Vakhshiteh F, Shamsian A, Sharifzadeh M, Kaghazian H, Mosaddegh MH. Erythropoietin-loaded solid lipid nanoparticles: Preparation, optimization, and in vivo evaluation. Colloids and Surfaces B: Biointerfaces. 2019; 178:307-16. DOI:10.1016/j. colsurf 2019.01.027.
  19. Zafar A, Alruwaili NK, Imam SS, Alsaidan OA, Ahmed MM, Yasir M, Warsi MH, Alquraini A, Ghoneim MM, Alshehri S. Development and optimization of hybrid polymeric nanoparticles of apigenin: Physicochemical characterization, antioxidant activity and cytotoxicity Sensors. 2022; 22(4):1364. DOI: 10.3390/s22041364
  20. Dave V, Sharma S, Yadav RB, Agarwal Herbal liposome for the topical delivery of ketoconazole for the effective treatment of seborrheic dermatitis. Applied Nanoscience. 2017:973-87. DOI: 10.1007/s13204-017-0634-3
  21. Mamatha P, Bhikshapathi DVRN. Preparation and In-vitro Evaluation of Pemigatinib Nanosponges Tablets by Box-Behnken International Journal of Pharmaceutical Quality Assurance. 2023;14(3):791-800.
  22. El-Menshawe SF, Kharshom R, El Sisi A. Preparation and optimization of buccal propranolol hydrochloride nanoethosomal gel: a novel approach for enhancement of bioavailability. Journal of Nanomedicine & 2017;8(2):1000435. DOI:10.4172/2157-7439.1000435
  23. Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, Xie DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. The AAPS journal. 2010; 12:263-71. DOI: 10.1208/s12248-010-9185-1
  24. Mahendran G, Manoj M, Prasad KR, Bai Antioxidants, anti- proliferative, anti-inflammatory, antidiabetic and antimicrobial effects of isolated compounds from Swertia corymbosa (Grieb.) Wight ex CB Clark–An in vitro approach. Food Science and Human Wellness. 2015 ;4(4):169-79. DOI:10.1016/j. fshw.2015.08.003
  25. Pulipaka S, Suttee A, Kumar MR, Kasarla Exploration of In-vitro Antidiabetic Activity of ZnO NPs and Ag NPs Synthesized using Methanolic Extracts of Alpinia mutica and Tradescantia spathaeca Leaves. International Journal of Pharmaceutical Quality Assurance. 2023;14(3):464-469.
  26. Swati A, Negi PS and Meena HS. A Comparative evaluation of in vitro anti-inflammatory and antifungal activity of Ganoderma lucidum strains DARL-4 and MS-1. International Journal of Green Pharmacy. 2018; 12:S126-S130.
  27. Gulluce M, Sahin F, Sokmen MÜ, Ozer H, Daferera D, Sokmen AT, Polissiou M, Adiguzel AY, Ozkan Hİ. Antimicrobial and antioxidant properties of the essential oils and methanol extract from Mentha longifolia ssp. longifolia. Food chemistry. 2007; 103(4):1449-56. DOI:10.1016/j.foodchem.2006.10.061
  28. Morimoto Y, Aiba Y, Miyanaga K, Hishinuma T, Cui L, Baba T, Hiramatsu K. CID12261165, a f lavonoid compound as antibacterial agents against quinolone-resistant Staphylococcus Scientific Reports. 2023;13(1):1725. DOI: 10.1038/s41598- 023-28859-8
  29. Kondo S, Ikeda Y, Hattori S, Hamada M, Takeuchi T. Susceptibility of methicillin-resistant Staphylococcus aureus to various Classification by aminoglycoside-modifying enzymes and antibiotics active against MRSA. The Japanese Journal of Antibiotics. 1991; 44(11):1211-5. PMID: 1664469
  30. Kornder Streptomycin revisited: molecular action in the microbial cell. Medical hypotheses. 2002; 58(1):34-46. DOI: 10.1054/mehy.2001.1450.
  31. Sharma D, Rajput J, Kaith BS, Kaur M, Sharma S. Synthesis of ZnO nanoparticles and study of their antibacterial and antifungal Thin solid films. 2010; 519(3):1224-9. DOI:10.1016/j. tsf.2010.08.073
  32. Ilk S, Saglam N, Özgen Kaempferol loaded lecithin/chitosan nanoparticles: Preparation, characterization, and their potential applications as a sustainable antifungal agent. Artificial cells, nanomedicine, and biotechnology. 2017; 45(5):907-16. DOI:10. 1080/21691401.2016.1192040
  33. Pool H, Quintanar D, de Dios Figueroa J, Mano CM, Bechara JE, Godínez LA, Mendoza S. Antioxidant effects of quercetin and catechin encapsulated into PLGA nanoparticles. Journal of nanomaterials. 2012;2012:86. DOI:10.1155/2012/145380
  34. Barbieri S, Sonvico F, Como C, Colombo G, Zani F, Buttini F, Bettini R, Rossi A, Colombo P. Lecithin/chitosan controlled release nanopreparations of tamoxifen citrate: loading, enzyme- trigger release and cell uptake. Journal of Controlled Release. 2013; 167(3):276-83. DOI:10.1016/j.jconrel.2013.02.009
  35. Souza MP, Vaz AF, Correia MT, Cerqueira MA, Vicente AA, Carneiro-da-Cunha MG. Quercetin-loaded lecithin/chitosan nanoparticles for functional food applications. Food and bioprocess technology. 2014:1149-59. DOI: 10.1007/s11947-013- 1160-2
  36. Elmas A, Akyüz G, Bergal A, Andaç M, Andaç Ö. Mathematical modelling of drug release. Research on Engineering Structures and Materials. 2020;6(4). DOI:10.17515/resm2020.178na0122
  37. Dharmadeva S, Galgamuwa LS, Prasadinie C, KumarasingheIn vitro anti-inflammatory activity of Ficus racemosa L. bark using albumin denaturation method. Ayu. 2018; 39(4):239. DOI: 10.4103/ayu.AYU_27_18
  38. Wall C, Lim R, Poljak M, Lappas M. Dietary flavonoids as therapeutics for preterm birth: luteolin and kaempferol suppress inflammation in human gestational tissues in vitro. Oxidative medicine and cellular 2013. DOI:10.1155/2013/485201
  39. Yang Y, Chen Z, Zhao X, Xie H, Du L, Gao H, Xie Mechanisms of Kaempferol in the treatment of diabetes: A comprehensive and latest review. Frontiers in Endocrinology. 2022; 13:990299. DOI:10.3389/fendo.2022.990299
  40. Li AP, He YH, Zhang SY, Shi YP. Antibacterial activity and action mechanism of flavonoids against phytopathogenic Pesticide Biochemistry and Physiology. 2022; 188:105221. DOI: 10.1016/j.pestbp.2022.105221