Development and Characterization of Gingerol-Assisted Silver Nanoparticle and Chitosan Alginate Membrane for Antibacterial and Wound Healing Activity
Manisha Khaire, Papiya Bigoniya*
DSKM College of Pharmacy, Faculty of Pharmacy, RKDF University, Bhopal, Madhya Pradesh, India.
Received: 08th March, 2024; Revised: 26th May, 2024; Accepted: 02nd August, 2024; Available Online: 25th September, 2024
ABSTRACT
This study synthesized and characterized gingerol-loaded silver nanoparticles (Ag-NPs), which were incorporated into chitosan-alginate (Cs/Alg) films for advanced wound care applications. Gingerol was isolated with a 9.81% yield, forming pale-yellow needle-shaped crystals with a melting point of 32ºC. The purity and structure of gingerol were confirmed through thin-layer chromatography (TLC), UV-visible, fourier-transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC) analyses. The synthesized Ag-NPs, particularly from the GN3 batch, exhibited a small particle size (36.52 ± 3.52 nm), high stability (zeta potential of -23.20 mV), and notable encapsulation efficiency (76.35%) and yield (74.11%). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses revealed their spherical and smooth morphology. Stability tests over three months showed no substantial changes in particle size, ZP, or %EE. The Cs/Alg films demonstrated appropriate thickness, weight, water uptake, and pH changes, with GN-CM4 showing the best performance. In-vitro drug release studies indicated increased release rates, especially for GN-CM4, which also exhibited the highest antibacterial activity. In-vivo studies on excision and burn wound models showed that GN-CM4 promoted complete wound closure by day 21, enhanced hydroxyproline levels, reduced myeloperoxidase content, and facilitated superior tissue regeneration. These findings underscore the potential of gingerol-loaded Ag-NPs in enhancing wound healing through their anti-inflammatory and antibacterial properties.
Keywords: Gingerol, Silver nanoparticles, Chitosan alginate (Cs/Alg) film, Infected incision wound, Burn wound, wound
healing
International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.3.29
How to cite this article: Khaire M, Bigoniya P. Development and Characterization of Gingerol-Assisted Silver Nanoparticle and Chitosan Alginate Membrane for Antibacterial and Wound Healing Activity. International Journal of Drug Delivery Technology. 2024;14(3):1456-1468.
REFERENCES
- Rani Raju N, Silina E, Stupin V, Manturova N, Chidambaram SB, Achar Multifunctional and Smart Wound Dressings—A Review on Recent Research Advancements in Skin Regenerative Medicine. Pharmaceutics. 2022 Jul 28;14(8):1574.
- Oliveira A, Simões S, Ascenso A, Reis Therapeutic advances in wound healing. Journal of Dermatological Treatment. 2022 Jan 2;33(1):2-2.
- Ameen F, Srinivasan P, Selvankumar T, Kamala-Kannan S, Al Nadhari S, Almansob A, Dawoud T, Govarthanan M. Phytosynthesis of Ag-NP utilizing Mangifera indica flower extract as bioreductant and their broad-spectrum antibacterial activity. Bioorganic Chemistry. 2019 Jul 1;88:102970. DOI: https://doi.org/10.1016/j.bioorg.2019.102970
- Bayda S, Adeel M, Tuccinardi T, Cordani M, Rizzolio F. The history of nanoscience and nanotechnology: from chemical– physical applications to Molecules. 2019;25(1):112. DOI: https://doi.org/10.3390/molecules25010112
- Bilgen F, Ural A, Kurutas EB, Bekerecioglu The effect of oxidative stress and Raftlin levels on wound healing. International wound journal. 2019;16(5):1178-1184. DOI: https:// doi.org/10.1111/iwj.13177
- Caetano GF, Frade MA, Andrade TA, Leite MN, Bueno CZ, Moraes ÂM, Ribeiro‐Paes JT. Chitosan‐alginate membranes accelerate wound healing. Journal of Biomedical Materials Research Part B: Applied 2015;103(5):1013-1022. DOI: https://doi.org/10.1002/jbm.b.33277
- Ali BH, Blunden G, Tanira MO, Nemmar Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food and chemical Toxicology. 2008;46(2):409-420. DOI: https://doi.org/10.1016/j. fct.2007.09.085
- Mao QQ, Xu XY, Cao SY, Gan RY, Corke H, Beta T, Li HB. Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe). Foods. 2019;8(6):185. DOI: https://doi. org/10.3390/foods8060185
- Shaukat MN, Nazir A, Fallico B. Ginger bioactives: A comprehensive review of health benefits and potential food applications. Antioxidants. 2023;12(11):2015. DOI: https://doi. org/10.3390/antiox12112015
- Alharbi KS, Nadeem MS, Afzal O, Alzarea SI, Altamimi AS, Almalki WH, Mubeen B, Iftikhar S, Shah L, Kazmi Gingerol, a natural antioxidant, attenuates hyperglycemia and downstream complications. Metabolites. 2022;12(12):1274. DOI: https://doi. org/10.3390/metabo12121274
- Bischoff-Kont I, Fürst R. Benefits of ginger and its constituent 6-shogaol in inhibiting inflammatory Pharmaceuticals. 2021;14(6):571. DOI: https://doi.org/10.3390/ph14060571
- Diniz FR, Maia RC, de Andrade LR, Andrade LN, Vinicius Chaud M, da Silva CF, Corrêa CB, de Albuquerque Junior RL, Pereira da Costa L, Shin SR, Hassan S. Silver nanoparticles- composing alginate/gelatine hydrogel improves wound healing in-vivo. 2020;10(2):390. DOI: https://doi.org/10.3390/nano10020390
- Shehabeldine AM, Salem SS, Ali OM, Abd-Elsalam KA, Elkady FM, Hashem Multifunctional silver nanoparticles based on chitosan: Antibacterial, antibiofilm, antifungal, antioxidant, and wound-healing activities. Journal of Fungi. 2022;8(6):612. DOI: https://doi.org/ 10.3390/jof8060612
- Pansara C, Mishra R, Mehta T, Parikh A, Garg S. Formulation of chitosan stabilized silver nanoparticle-containing wound healing film: in-vitro and in-vivo Journal of pharmaceutical sciences. 2020;109(7):2196-2205. DOI:10.1016/j. xphs.2020.03.028
- Zhang M, Wang G, Wang D, Zheng Y, Li Y, Meng W, Zhang X, Du F, Lee S. Ag@ MOF-loaded chitosan nanoparticle and polyvinyl alcohol/sodium alginate/chitosan bilayer dressing for wound healing applications. International Journal of Biological 2021;175:481-494. DOI:10.1016/j. ijbiomac.2021.02.045
- Jamaluddin AW, Lestari A. Effectiveness of ginger ointment (Zingiber officinale Roscoe) on incision wound healing in white rats (Rattus norvegicus). Jurnal Riset Veteriner Indonesia (Journal of The Indonesian Veterinary Research). 2021;5(1):20- 26 DOI: https://doi.org/10.20956/jrvi.v5i1.13060
- Bouchama C, Zinedine A, Rocha JM, Chadli N, El Ghadraoui L, Chabir R, Raoui SM, Errachidi Effect of phenolic compounds extracted from turmeric (Curcuma longa L.) and ginger (Zingiber officinale) on cutaneous wound healing in Wistar rats. Cosmetics. 2023;10(5):137. DOI:10.3390/cosmetics10050137
- Aleem M, Khan MI, Shakshaz FA, Akbari N, Anwar Botany, phytochemistry and antimicrobial activity of ginger (Zingiber officinale): A review. The International Journal of Herbal Medicine. 2020;8(6):36-49. DOI:10.22271/flora.2020.v8.i6a.705
- Khurana RK, Rao S, Beg S, Katare OP, Singh B. Systematic development and validation of a thin-layer densitometric bioanalytical method for estimation of gingerol employing analytical quality by design (AQbD) approach. Journal of Chromatographic Science. 2016;54(5):829-841. DOI: https:// oup.com/chromsci/article/54/5/829/1745060
- Lwin OM, Giribabu N, Kilari EK, Salleh Topical administration of gingerol promotes healing of the wound of streptozotocin- nicotinamide-induced type-2 diabetic male rats. Journal of Dermatological Treatment. 2021;32(8):1039-1048. DOI: https:// doi.org/10.1080/09546634.2020.1721419
- Mahendran S, Badami S, Ravi S, Thippeswamy BS, Veerapur VP. Synthesis and evaluation of analgesic and anti- inflammatory activities of most active free radical scavenging derivatives of gingerol. British Journal of Applied Science & 2014;4(35):4959-4973. DOI: https://doi.org/10.9734/ BJAST/2014/12745
- Furniss BS, Hannaford AJ, Smith PWG, Tatchell AR. Vogel’s, Textbook of Practical Organic Chemistry, 5th edition, Longman Scientific and Technical, 1989: 236-240. DOI: https:// faculty.ksu.edu.sa/sites/default/files/vogel_-_practical_organic_ chemistry_5th_edition.pdf
- Biswas T, Sen A, Roy R, Maji S, Maji Isolation of gingerol from flowering buds of Mangifera indica L and its evaluation of in-vitro antibacterial activity. Journal of Pharmaceutical Analysis. 2015;4(3):49-56.
- Meng X, Tian F, Yang J, He CN, Xing N, Li F. Chitosan and alginate polyelectrolyte complex membranes and their properties for wound dressing application. Journal of Materials Science:Materials in Medicine. 2010;21:1751-1759. DOI: https://doi. org/10.1007/s10856-010-3996-6
- Espinosa-Espinosa L, Garduño-Siciliano L, Rodriguez-Canales M, Hernandez-Portilla LB, Canales-Martinez MM, Rodriguez- Monroy The wound-healing effect of mango peel extract on incision wounds in a murine model. Molecules. 2022;27(1):259. DOI: https://doi.org/10.3390/molecules27010259
- Muruganandan S, Lal J, Gupta PK. Immunotherapeutic effects of gingerol mediated by the inhibition of oxidative stress to activated lymphocytes, neutrophils and macrophages. 2005;215(1-2):57-68. DOI: https://doi.org/10.1016/j. tox.2005.06.008
- Nnamdi Development and characterization of mucoadhesive patches for buccal delivery of pregabalin. Universal Journal of Pharmaceutical Research. 2017;2(3):6-9. DOI: https://doi. org/10.22270/ujpr.v2i3.R2
- Othman SN, Seka In-vitro antioxidant and cytotoxic activities of Ag-NP of gingerol isolated from Mangifera indica. Journal of Global Pharma Technology. 2019;11(6):10-15.
- Paul W, Sharma Chitosan and alginate wound dressings: a short review. Trends in Biomaterials and Artificial Organs. 2004;18(1):18-23. DOI: https://tarjomefa.com/wp-content/ uploads/2016/09/5300-English.pdf
- Prajapati B, Raichandani Y, Patel R, Sawant K. Chitosan alginate film for topical drug delivery of antimicrobial agents. Current Pharmaceutical Research Journal. 2007;1(03):66-74. DOI: https://researchgate.net/publication/291116073_ Chitosan_Alginate_Film_For_Topical_Drug_Delivery_Of_ Antimicrobial_Agents
- Rajendran P, Ekambaram G, Magesh V, Sakthisekaran D. Chemopreventive efficacy of gingerol against benzo (a) pyrene induced lung carcinogenesis in experimental animals. Environmental Toxicology and 2008;26(3):278-DOI: https://doi.org/10.1016/j.etap.2008.05.005
- Rasyid R, Ruslan R, Mawaddah S, Rivai H. Quantitative determination of gingerol in methanol extract of bacang mango (Mangifera foetida L.) leaves by thin-layer chromatography densitometry. World Journal of Pharmacy and Pharmaceutical Sciences.2020; 9(7):1551-1560. DOI: http://www.wjpps.com/
- Samadarsi R, Dutta Design and characterization of gingerol nanoparticles for oral delivery. Journal of Food Engineering. 2019;247:80-94. DOI: https://doi.org/10.1016/j. jfoodeng.2018.11.020
- Sharma S, Sanpui P, Chattopadhyay A, Ghosh Fabricationof antibacterial silver nanoparticle—sodium alginate–chitosan composite films. RSC Advances. 2012;2(13):5837-5843. DOI: https://doi.org/10.1039/C2RA00006G
- Sushanth KA, Lakshmi KC, Reddy DS. Evaluation of wound healing activity with a new formulation of dry Mangifera indica and honey utilizing swiss albino Asian Journal of Pharmaceutical and Clinical Research. 2016:139-142. DOI:file:///C:/Users/admin/Downloads/admin,+Journal+manager,+ AJPCR_11810_RA.pdf
- Tenorová K, Masteiková R, Pavloková S, Kostelanská K, Bernatonienė J, Vetchý D. Formulation and evaluation of novel film wound dressing based on collagen/microfibrillated carboxymethylcellulose blend. Pharmaceutics. 2022;14(4):782. DOI: https://doi.org/10.3390/pharmaceutics14040782
- Vandeputte OM, Kiendrebeogo M, Rasamiravaka T, Stevigny C, Duez P, Rajaonson S, Diallo B, Mol A, Baucher M, El JaziriThe flavanone naringenin reduces the production of quorum sensing-controlled virulence factors in Pseudomonas aeruginosa PAO1. Microbiology. 2011;157(7):2120-2132. DOI: https://doi. org/10.1099/mic.0.049338-0
- Vyas A, Syeda K, Ahmad A, Padhye S, H Sarkar Perspectives on medicinal properties of gingerol. Mini Reviews in Medicinal Chemistry. 2012;12(5):412-425. DOI: https://doi. org/10.2174/138955712800493870
- Kadhim O, Al-demirchi JY, Al-Hussainawy MK, Al-Hamdani MM, Kadhim Efficiency of Phenazine Compound Produced by Rhizospheric Pseudomonas f luorescens against Few Pathogenic Bacteria Isolated from Ear Infections. International Journal of Drug Delivery Technology. 2023;13(4):1167-1171. DOI: 10.25258/ijddt.13.4.07
- Ismail WF, Al-Mudhafar MMJ, Fadhil AA, Synthesis, Characterization of New Isatin-Ibuprofen Derivatives with Expected Biological Activity. International Journal of Drug Delivery Technology. 2022;12(4):1560-1565. DOI: 10.25258/ 12.4.13
- Mohammed RH, AlـNiaame AE. Evaluation of the Biological Efficacy and Physicochemical Evaluation of Toothpaste Prepared from Few Types of Plant Extracts against Some Pathogenic Bacteria Isolated from the International Journal of Drug Delivery Technology. 2022;12(4):1626-1631. DOI: 10.25258/ ijddt.12.4.25
- Mathew S, Sankarganesh P, Joseph Ecotoxicological Effects of Lead Exposed Cyprinus carpio and HSP70-Induced Antioxidants against ROS. International Journal of Drug Delivery Technology. 2023;13(4):1178-1182. DOI: 10.25258/ijddt.13.4.09