Skip to main content

Advertisement

SpringerLink
Log in

In vivo therapeutic efficacy of Curcuma longa extract loaded ethosomes on wound healing

  • Original Article
  • Published:
Veterinary Research Communications Aims and scope Submit manuscript

Abstract

Since ancient times, medicinal plants are widely accepted to promote the health and wellness of animals and mankind. The medicinal plant-based therapies have limitations of delayed onset of action, inconsistent absorption, low bioavailability, oxidation, and poor solubility. The encapsulation studies suggested improved efficacy. Therefore, the present study attempts to evaluate the efficacy of Curcuma longa extracts encapsulated in Ethosome on wound healing model compared to crude extract. The Curcuma longa extract swere prepared by cold percolation method and total curcuminoid content was determined by Reverse phase-HPLC. Three Ethosomal suspensions (ETS1, ETS2, and ETS3) were prepared and characterized for particle distribution, morphology, and absorption spectrum by Zetasizer, Scanning Electron Microscopy, and FTIR respectively. The Ethosomal suspension with the highest entrapment efficiency was applied topically at a varying concentrations (0.25, 0.5, and 1 g/cm2) on the surgically created wounds in rats. The efficacy of wound healing was evaluated by clinical observation, macroscopic evaluation of granulation tissue, colour digital image processing, and histology. The methanolic extract of Curcuma longa showed better antibacterial potential than ethanolic and aqueous. The total Curcuminoid content in the Curcuma longa rhizome was 4.03%. The size, PDI, zeta potential, and viscosity of Ethosomal suspension ranged from 34.8 to 371 nm, 0.236–1.178, 15.6-36.8mV, and 0.8460–0.8510, respectively. The ETS3 was found the most optimum combination with the highest entrapment efficiency and the topical application at a dose rate of 0.5 g/cm2 and 1.0 g/cm2 resulted in comparable wound contracture, pain score, histopathological score as compared to control groups.It was concluded that the Curcuma longa encapsulation in Ethosome resulted in improved wound appearance, granulation tissue score, and appearance with a shortened period of wound resolution at the cellular level as compared to crude extract.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

The dataset generated during the study is provided as 34 and also available with corresponding author which will be made available on request.

References

  • Ajige L, Sunday T, Elkanah F et al (2017) Comparative study of antibacterial effects of Curcuma longa Linn. and Zingiber officinale Rosc. Rhizomes. Microbiol Res J Int 18:1–8. https://doi.org/10.9734/mrji/2017/31551

    Article  CAS  Google Scholar 

  • Akbik D, Ghadiri M, Chrzanowski W, Rohanizadeh R (2014) Curcumin as a wound healing agent. Life Sci 116:1–7

    CAS  PubMed  Google Scholar 

  • Alemi A, Zavar Reza J, Haghiralsadat F et al (2018) Paclitaxel and curcumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy. J Nanobiotechnol 16:1–20. https://doi.org/10.1186/s12951-018-0351-4

    Article  CAS  Google Scholar 

  • Antony B, Benny M, Rao SB (2005) Enhancing the absorption of curcuminoids. Spice India 23:26

    Google Scholar 

  • Asai A, Miyazawa T (2000) Occurrence of orally administered curcuminoid as glucuronide and glucuronide/sulfate conjugates in rat plasma. Life Sci 67:2785–2793. https://doi.org/10.1016/S0024-3205(00)00868-7

    Article  CAS  PubMed  Google Scholar 

  • Ashraf K, Mujeeb M, Ahmad A et al (2015) Determination of Curcuminoids in Curcuma longa Linn. by UPLC/Q-TOF–MS: An Application in Turmeric Cultivation. J Chromatogr Sci 53:1346–1352. https://doi.org/10.1093/chromsci/bmv023

    Article  CAS  PubMed  Google Scholar 

  • Athira GK, Jyothi AN (2014) Preparation and characterization of curcumin loaded cassava starch nanoparticles with improved cellular absorption. Int J Pharm Pharm Sci 6:171–176

    CAS  Google Scholar 

  • Atkins E, Bodel P (1972) Physiology in medicine: fever. N Eng J Med 286:27–34

    CAS  Google Scholar 

  • Atmakuri LR, Dathi S (2010) Current trends in herbal medicines. J Pharm Res 3:109–113

    Google Scholar 

  • Bigbie RB, Schumacher J, Swaim SF et al (1991) Effects of amnion and live yeast cell derivative on second-intention healing in horses. Am J Vet Res 52:1376–1382

    CAS  PubMed  Google Scholar 

  • Bonté F, Noel-Hudson MS, Wepierre J, Meybeck A (1997) Protective effect of curcuminoids on epidermal skin cells under free oxygen radical stress. Planta Med 63:265–266. https://doi.org/10.1055/s-2006-957669

    Article  PubMed  Google Scholar 

  • Borena B, Pawde A, Aithal H et al (2010) Evaluation of autologous bone marrow-derived nucleated cells for healing of full-thickness skin wounds in rabbits. Int Wound J 7:249–260. https://doi.org/10.1111/j.1742-481X.2010.00683.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Celia C, Cilurzo F, Trapasso E et al (2012) Ethosomes® and transfersomes® containing linoleic acid: Physicochemical and technological features of topical drug delivery carriers for the potential treatment of melasma disorders. Biomed Microdevices 14:119–130. https://doi.org/10.1007/s10544-011-9590-y

    Article  CAS  PubMed  Google Scholar 

  • Chaudhary H, Kohli K, Kumar V (2013) Nano-transfersomes as a novel carrier for transdermal delivery. Int J Pharm 454:367–380

    CAS  PubMed  Google Scholar 

  • Chauhan P, Keni K, Patel R (2017) Investigation of phytochemical screening and antimicrobial activity of Curcuma longa. Int J Adv Res Biol Sci 4:153–163

    CAS  Google Scholar 

  • Chen J, Dai WT, He ZM, Gao L, Huang X, Gong JM, Xing HY, Chen WD (2013) Fabrication and Evaluation of Curcumin-loaded Nanoparticles Based on Solid Lipid as a New Type of Colloidal Drug Delivery System. Ind J Pharma Sci 75(2):178–184

    CAS  Google Scholar 

  • Dayan N, Touitou E (2000) Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes. Biomaterials 21:1879–1885

    CAS  PubMed  Google Scholar 

  • Fatima Grace X, Rahul Raj S, Reshma I et al (2014) Herbal ethosomes-A novel approach in herbal drug technology. Am J Ethnomed 1:226–230

    Google Scholar 

  • Ghamsari SM, Acorda JA, Taguchi K et al (1996) Evaluation of wound healing of the teatwith and without low level laser therapy in dairy cattle by laser doppler flowmetry in comparison with histopathology, tensiometry and hydroxyproline analysis. Br Vet J 152:583–592

    CAS  PubMed  Google Scholar 

  • Gunjan J, Swarnlata S (2014) Topical delivery of Curcuma longa extract loaded nanosized ethosomes to combat facial wrinkles. J Pharm Drug Deliv Res 3 3:1000118

    Google Scholar 

  • Hadgraft J (2004) Skin deep. Eur J Pharm Biopharm 58:291–299

    CAS  PubMed  Google Scholar 

  • Hadi S, Artanti AN, Rinanto Y, Wahyuni DSC (2018) Curcuminoid content of Curcuma longa L. and Curcuma xanthorrhiza rhizome based on drying method with NMR and HPLC-UVD. In: IOP Conference Series: Materials Science and Engineering. IOP Publishing, p 12058

  • Hashemi SA, Madani SA, Abediankenari S (2015) The review on properties of aloe vera in healing of cutaneous wounds. Biomed Res Int 2015. https://doi.org/10.1155/2015/714216

  • Holleran WM, Takagi Y, Uchida Y (2006) Epidermal sphingolipids: metabolism, function, and roles in skin disorders. FEBS Lett 580:5456–5466

    CAS  PubMed  Google Scholar 

  • Institute undefined C and LS (2016) Clinical & Laboratory Standards Institute: CLSI Guidelines. https://clsi.org/media/2663/m100ed29_sample.pdf

  • Jagetia GC, Rajanikant GK (2004) Role of curcumin, a naturally occurring phenolic compound of turmeric in accelerating the repair of excision wound, in mice whole-body exposed to various doses of γ-radiation. J Surg Res 120:127–138

    CAS  PubMed  Google Scholar 

  • Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK (2002) Improved HPLC method for the determination of curcumin, demethoxycurcumin, and bisdemethoxycurcumin. J Agric Food Chem 50:3668–3672

    CAS  PubMed  Google Scholar 

  • Jin-guang C, Wei LAI, Yu J (2013) Preparation of curcumin ethosomes. Afr J Pharm Pharmacol 7:2246–2251

    Google Scholar 

  • Jurenka JS (2009) Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 4(2):141–153

    Google Scholar 

  • Lopez-Pinto JM, Gonzalez-Rodriguez ML, Rabasco AM (2005) Effect of cholesterol and ethanol on dermal delivery from DPPC liposomes. Int J Pharm 298:1–12

    CAS  PubMed  Google Scholar 

  • Luna LG (1968) Methods for carbohydrates and mucoproteins. Man Histol Stain methods armed forces, 3rd ed. Blakiston Division, McGraw-Hill

  • Mailafiya MM, Abubakar K, Danmaigoro A et al (2019) Evaluation of in vitro release kinetics and mechanisms of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles. Biomed Res Ther 6(12):3518–3540. https://doi.org/10.15419/bmrat.v6i12.580

  • Madhavi BB, Vennela KS, Masana P, Madipoju B (2013) Enhanced transdermal drug penetration of curcumin via ethosomes. Malaysian J Pharm Sci 11:49

    Google Scholar 

  • Manca ML, Zaru M, Manconi M et al (2013) Glycerosomes: a new tool for effective dermal and transdermal drug delivery. Int J Pharm 455:66–74

    CAS  PubMed  Google Scholar 

  • Manosroi A, Jantrawut P, Khositsuntiwong N et al (2009) Novel elastic nanovesicles for cosmeceutical and pharmaceutical applications. Chiang Mai J Sci 36:168–178

    CAS  Google Scholar 

  • Marchal-Heussler L, Maincent P, Hoffman M et al (1990) Antiglaucomatous activity of betaxolol chlorhydrate sorbed onto different isobutylcyanoacrylate nanoparticle preparations. Int J Pharm 58:115–122. https://doi.org/10.1016/0378-5173(90)90248-3

    Article  CAS  Google Scholar 

  • Masson P (1929) Some histological methods: trichrome staining and their preliminary technique. J Tech Methods 12:75–90

    Google Scholar 

  • Mathew DD, Sharma AK, Kumar N et al (2019) Healing potency of bone marrow derived mesenchymal stem cells from rat and dogs for wound healing in a rat model. Trends Biomater Artif Organs 33(2):30–46

    Google Scholar 

  • Mohanty C, Acharya S, Mohanty AK et al (2010) Curcumin-encapsulated MePEG/PCL diblock copolymeric micelles: a novel controlled delivery vehicle for cancer therapy. Nanomedicine 5:433–449

    CAS  PubMed  Google Scholar 

  • Mukherjee PK, Harwansh RK, Bhattacharyya S (2015) Bioavailability of herbal products: approach toward improved pharmacokinetics. Evidence-Based Validation of Herbal Medicine. Elsevier, pp 217–245

  • National Committee for Clinical Laboratory Standards [WorldCat Identities]. http://worldcat.org/identities/lccn-n82041728/. Accessed 8 Mar 2021

  • Natsheh H, Touitou E (2020) Phospholipid Vesicles for Dermal/Transdermal and Nasal Administration of Active Molecules: The Effect of Surfactants and Alcohols on the Fluidity of Their Lipid Bilayers and Penetration Enhancement Properties. Molecules 25:2959. https://doi.org/10.3390/MOLECULES25132959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neagoş D, Mitran V, Chiracu G et al (2006) Skin wound healing in a free floating fibroblast populated collagen lattice model. Rom J Biophys 16:157–168

    Google Scholar 

  • Orsted L, Heather KD, Louise LF (2004) Principles of wound healing. Wound Care Canada 9:4–12. https://doi.org/10.1142/9789812791535_0028

    Article  Google Scholar 

  • Partoazar A, Kianvash N, Darvishi MH et al (2016) Ethosomal curcumin promoted wound healing and reduced bacterial flora in second degree burn in rat. Drug Res (Stuttg) 66:660–665

    CAS  PubMed  Google Scholar 

  • Pathan IB, Jaware BP, Shelke S, Ambekar W (2018) Curcumin loaded ethosomes for transdermal application: Formulation, optimization, in-vitro and in-vivo study. J Drug Deliv Sci Technol 44:49–57

    CAS  Google Scholar 

  • Patwardhan B, Warude D, Pushpangadan P, Bhatt N (2005) Ayurveda and traditional Chinese medicine: A comparative overview. Evidence-based Complement. Altern Med 2:465–473

    Google Scholar 

  • Petrie A, Watson P (2006) Additional techniques. Stat Vet Anim Sci 191–211

  • Prabaningdyah NK, Riyanto S, Rohman A (2018) Application of FTIR spectroscopy and multivariate calibration for analysis of curcuminoid in syrup formulation. J Appl Pharm Sci 8:172–179. https://doi.org/10.7324/JAPS.2018.8324

    Article  CAS  Google Scholar 

  • Rakesh R, Anoop KR (2012) Formulation and optimization of nano-sized ethosomes for enhanced transdermal delivery of cromolyn sodium. J Pharm Bioallied Sci 4:333

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ramadon D, Goldie AW, Anwar E (2017) Novel transdermal ethosomal gel containing green tea (Camellia sinensis L. Kuntze) leaves extract: formulation and in vitro penetration study. J Young Pharm 9:336

    CAS  Google Scholar 

  • Reinke JM, Sorg H (2012) Wound repair and regeneration. Eur Surg Res 49:35–43

    CAS  PubMed  Google Scholar 

  • Samnani A, Shahwal V, Bhowmick M et al (2012) Design and evaluation of ultradeformable soft elastic nano vesicle ethosomes for dermal delivery. Int J Biomed Adv Res 3:111–117

    CAS  Google Scholar 

  • Schallberger SP, Stanley BJ, Hauptman JG, Steficek BA (2008) Effect of porcine small intestinal submucosa on acute full-thickness wounds in dogs. Vet Surg 37:515–524

    PubMed  Google Scholar 

  • Schieffer GW (2002) Pressurized liquid extraction of curcuminoids and curcuminoid degradation products from turmeric (Curcuma longa) with subsequent HPLC assays. J Liq Chromatogr Relat Technol 25:3033–3044

    Google Scholar 

  • Seema A (2014) Recent development of herbal formulation—a novel drug delivery system. Int Ayurvedic Med J 2:952–958

    Google Scholar 

  • Sidhu GS, Singh AK, Thaloor D et al (1998) Enhancement of wound healing by curcumin in animals. Wound Repair Regen 6:167–177. https://doi.org/10.1046/j.1524-475X.1998.60211

    Article  CAS  PubMed  Google Scholar 

  • Sinico C, Fadda AM (2009) Vesicular carriers for dermal drug delivery. Expert Opin Drug Deliv 6:813–825

    CAS  PubMed  Google Scholar 

  • Snedecor GW, Cochran WG (1989) Statistical methods, 8thEdn. Ames Iowa State Univ Press Iowa 54:71–82

    Google Scholar 

  • Srivastava N, Singh K, Amrit K (2015) Formulation and evaluation of seabuckthorn leaf extract loaded ethosomal gel. Asian J Pharm Clin Res 8:316–320

    Google Scholar 

  • Sujatha V, Vishnuvaravidyadhar T, Parvathi M, Reddy S (2021) A review on transdermal drug delivery system by ethosomes. Pharma News

  • Taverna D, Pollins AC, Sindona G et al (2015) Imaging mass spectrometry for assessing cutaneous wound healing: analysis of pressure ulcers. J Proteome Res 14:986–996

    CAS  PubMed  Google Scholar 

  • Tayyem RF, Heath DD, Al-Delaimy WK, Rock CL (2006) Curcumin content of turmeric and curry powders. Nutr Cancer 55:126–131

    CAS  PubMed  Google Scholar 

  • Thakur L, Ghodasra U, Patel N, Dabhi M (2011) Novel approaches for stability improvement in natural medicines. Pharmacogn Rev 5:48

    PubMed  PubMed Central  Google Scholar 

  • Touitou E(1998) Composition for applying active substances to or through the skin

  • Touitou E, Dayan N, Bergelson L et al (2000) Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release 65:403–418

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Authors thankfully acknowledge Dr. Karuna Shanker, Senior Scientist, CIMAP, Lucknow for providing raw the Curcuma longa rhizome and analysis of crucuminoid contents. The author are also thankful to Director, ICAR-IVRI, Izatnagar for providing necessary infrastructure facility.

Funding

The present work was conducted under master degree programme at Division of Medicine, ICAR-IVRI, Izatnagar with no seperate funding by any organisation.

Author information

Authors and Affiliations

  1. Division of Medicine, ICAR-Indian Veterinary Research Institute Izatnagar, 243122, Bareilly, Uttar Pradesh, India

    Sumit Kumar & Akhilesh Kumar

  2. Division of Surgery, ICAR-Indian Veterinary Research Institute Izatnagar, 243122, Bareilly, Uttar Pradesh, India

    Naveen Kumar

  3. Section of Biophysics & Electron Microscopy Section, Division of Biochemistry, ICAR-Indian Veterinary Research Institute Izatnagar, 243122, Bareilly, Uttar Pradesh, India

    Praveen Singh

  4. Division of Pharmacology & Toxicology, ICAR-Indian Veterinary Research Institute Izatnagar, 243122, Bareilly, Uttar Pradesh, India

    Thakur Uttam Singh

  5. Division of Epidemiology, ICAR-Indian Veterinary Research Institute Izatnagar, 243122, Bareilly, Uttar Pradesh, India

    Bhoj Raj Singh

  6. Department of Life Sciences, School of Basic Sciences and Research, Sharda University, 201310, Greater Noida, Uttar Pradesh, India

    Piyush Kumar Gupta

  7. Biorefining and Advanced Materials Research Centre, Scotland’s Rural College (SRUC), Kings Buildings, EH9 3JG, Edinburgh, UK

    Vijay Kumar Thakur

  8. Department of Mechanical Engineering, School of Engineering, Shiv Nadar University, 201314, Noida, Uttar Pradesh, India

    Vijay Kumar Thakur

  9. School of Engineering, University of Petroleum & Energy Studies (UPES), Dehradun, Uttarakhand, India

    Vijay Kumar Thakur

Authors
  1. Sumit Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akhilesh Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naveen Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Praveen Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thakur Uttam Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bhoj Raj Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Piyush Kumar Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vijay Kumar Thakur
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Authors (Sumit Kumar, Akhilesh Kumar, Naveen Kumar, Praveen Singh, Thakur Uttam Singh, Bhoj Raj Singh, Piyush Kumar Gupta, and Vijay Kumar Thakur) contibuted to cenceptualization and design of study. The experimentation and data collection was performed by Sumit Kumar, Akhilesh Kumar, Naveen Kumar and Praveen Singh. All the authors contributed subtantially in data analysis. The first draft of manuscript writted by Sumit Kumar and Akhilesh Kumar and all the authors mentioned in manuscript contributed in the revision of manuscipt to present form. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Akhilesh Kumar.

Ethics declarations

Conflict of interest

All the authors declare no conflict of interest.

Ethics approval

The animal experimentation protocols involved in this study was approved by the Institute Animal Ethics Committee (IAEC), ICAR-Indian Veterinary Research Institute, Izatnagar vide No.F.26 − 1/2018-19/J.D-R dated 05.08.2019.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 911 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, S., Kumar, A., Kumar, N. et al. In vivo therapeutic efficacy of Curcuma longa extract loaded ethosomes on wound healing. Vet Res Commun 46, 1033–1049 (2022). https://doi.org/10.1007/s11259-022-09952-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11259-022-09952-1

Keywords

Search

Navigation