DEVELOPMENT AND EVALUATION OF SILVER NANOPARTICLES-LOADED PHYTOGEL OF HYDROALCOHOLIC EXTRACT OF FICUS VIRENS BARK: FORMULATION, OPTIMIZATION, AND ANTIMICROBIAL EFFICACY

Authors

  • DEEPIKA AGGARWAL Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana-136119, India https://orcid.org/0000-0003-1305-3104
  • KAMAL SAROHA Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana-136119, India
  • MANJUSHA CHOUDHARY Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana-136119, India
  • KAMAL KAUSHIK Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, Haryana-136119, India https://orcid.org/0009-0003-1769-431X

DOI:

https://doi.org/10.22159/ijap.2025v17i6.56393

Keywords:

Silver nanoparticles, Phytogel, Herbal extract, Antimicrobial activity, Topical formulation, Green synthesis, Optimization, Agar well diffusion

Abstract

Objective: This study aimed to develop, optimize, and characterize a transdermal phytogel incorporating silver nanoparticles (AgNPs) loaded with Ficus virens hydroalcoholic bark extract, using Carbopol 940 as the gelling agent, to enhance antimicrobial efficacy and formulation stability.

Methods: This research involved the preparation of phytogel formulations by systematically varying the concentrations of Carbopol 940 and silver nanoparticles combined with hydroalcoholic Ficus virens bark extract (FV-BE). A Central composite design (CCD) was employed to optimize the formulations and evaluate the influence of independent factors on key formulation attributes. Comprehensive physicochemical evaluations, including measurements of pH, viscosity, spreadability, extrudability, drug content, entrapment efficiency, and stability, are conducted to ensure suitability for topical application. The nanoparticulate system was described via zeta potential, particle size, and polydispersity index (PDI) study. To further understand the release mechanisms, in vitro drug release and kinetic modeling were performed. The agar well diffusion method was used to evaluate the antibacterial activity against Aspergillus niger, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli.

Results: The optimized formulation (F7) containing 0.75% w/w Carbopol 940 and 0.02% w/w AgNPs with FV-BE exhibited desirable physicochemical properties, including suitable viscosity (5517±1.2 cps), spreadability (12.75±1.67 g. cm/s), pH (6.64±0.097), high entrapment efficiency (90.23±0.37%), and drug content (92.95%±1.12%). The average particle size was 259.5 nm with a PDI of 0.280, and the zeta potential was -26.5 mV, indicating moderate colloidal stability. In vitro drug release studies revealed a complete diffusion-controlled release over 24 h, fitting the Korsmeyer-Peppas model with a non-Fickian diffusion mechanism. The phytogel formulation demonstrated notable antimicrobial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Aspergillus niger, with inhibition zones comparable to standard antibiotics. Stability studies confirmed the formulation's robustness under various storage conditions over three months.

Conclusion: The developed phytogel incorporating FV-BE and AgNPs is a promising nanocarrier-based system for effective topical antimicrobial therapy. Further in vivo and clinical validations are warranted to advance its therapeutic application.

References

1. Patil PB, Datir SK, Saudagar RB. A review on topical gels as drug delivery system. J Drug Delivery Ther. 2019 May 2;9(3-s):989-94. doi: 10.22270/jddt.v9i3-s.2930.

2. Bhuyan C, Saha D, Rabha B. A brief review on topical gels as drug delivery system. J Pharm Res Int. 2021 Oct 26;33(47A):344-57. doi: 10.9734/jpri/2021/v33i47A33020.

3. Alberti I, Grenier A, Kraus H, Carrara DN. Pharmaceutical development and clinical effectiveness of a novel gel technology for transdermal drug delivery. Expert Opin Drug Deliv. 2005 Sep 1;2(5):935-50. doi: 10.1517/17425247.2.5.935, PMID 16296788.

4. Nidhi A. Bagmar, Pooja R. Hatwar, Prashant G. Shelke, Ravindra L. Bakal. A review on “Topical gels: an emerging drug delivery system”. GSC Biol PharmSci. 2024;28(2):285-96. doi: 10.30574/gscbps.2024.28.2.0311.

5. Sivadasan D, Madkhali OA. The design features, quality by design approach, characterization, therapeutic applications, and clinical considerations of transdermal drug delivery systems-A comprehensive review. Pharmaceuticals (Basel). 2024 Oct 9;17(10):1346. doi: 10.3390/ph17101346, PMID 39458987.

6. Jakasaniya P, Patel J, Dudhat K, Mori D. Formulation and optimization of gastro-retentive in situ gel of antiepileptic agent by using a Box–Behnken factorial design. Proc Indian Natl Sci Acad. 2025;91(1):285-98. doi: 10.1007/s43538-024-00343-5.

7. Amgaonkar YM, Kochar NI, Chandewar AV, Umekar MJ, Wadher KJ. Boswellic acid Loaded Nanoemulgel for Rheumatoid Arthritis: formulation Design and Optimization by QbD, in vitro, ex vivo, and in vivo evaluation. Ind J Pharm Edu Res. 2024 Apr 1;58(2):546-54. doi: 10.5530/ijper.58.2.61.

8. Saadh MJ, Mustafa MA, Kumar S, Gupta P, Pramanik A, Rizaev JA. Advancing therapeutic efficacy: nanovesicular delivery systems for medicinal plant-based therapeutics. Naunyn Schmiedebergs Arch Pharmacol. 2024 Oct;397(10):7229-54. doi: 10.1007/s00210-024-03104-9, PMID 38700796.

9. Ghosh B, Sarkar S, Ghosh S. Advancing sustainable wastewater treatment: unleashing the potential of nanosponges for effective remediation. In: Innovative and hybrid technologies for wastewater treatment and recycling. 2024. p. 381-404.

10. Dutta T, Barman A, Bhattacherjee S, Chakraborty J, Dutta T. Antimicrobial silver nanoparticles for water disinfection: a short review on recent advances. Nanotechnol Environ Eng. 2024 Mar;9(1):111-31. doi: 10.1007/s41204-023-00354-5.

11. Delgado Pujol EJ, Martinez G, Casado Jurado D, Vazquez J, Leon Barberena J, Rodríguez Lucena D. Hydrogels and nanogels: pioneering the future of advanced drug delivery systems. Pharmaceutics. 2025 Feb 7;17(2):215. doi: 10.3390/pharmaceutics17020215, PMID 40006582.

12. Modi DM, Modi AD. Nanogel-mediated therapeutic delivery across blood-cerebrospinal fluid and blood-spinal cord barriers. Brain Disord. Science Direct. 2024 Sep 1;15:100151. doi: 10.1016/j.dscb.2024.100151.

13. Herbig ME, Evers DH, Gorissen S, Köllmer M. Rational design of topical semi-solid dosage forms-how far are we? Pharmaceutics. 2023 Jun 26;15(7):1822. doi: 10.3390/pharmaceutics15071822, PMID 37514009.

14. Aggarwal D, Kamal CM, Agarwal G, Kumar A, Sharma D. Understanding of phyto-nanomedicine for the management of inflammation and wound healing: an outlook. Int J Pharm Sci Res. 2023 Oct;14(10):4713-23. doi: 10.13040/IJPSR.0975-8232.14(10).4713-23.

15. Simbine EO, Rodrigues LC, Lapa-guimaraes J, Kamimura ES, Corassin CH, Oliveira CA. Application of silver nanoparticles in food packages: a review. Food Sci Technol. 2019 Jun 27;39(4):793-802. doi: 10.1590/fst.36318.

16. Vijapur LS, Shalavadi M, Desai AR, Hiremath JN, Gudigennavar AS, Shidramshettar SL. Wound healing potential of green synthesized silver nanoparticles of Glycyrrhiza glabraLinn root extract: a preclinical study. J Trace Elem Min. 2025 Mar 1;11:100214. doi: 10.1016/j. jtemin.2025.100214.

17. Aldakheel FM, Sayed MM, Mohsen D, Fagir MH, El Dein DK. Green synthesis of silver nanoparticles loaded hydrogel for wound healing; systematic review. Gels. 2023 Jun 29;9(7):530. doi: 10.3390/gels9070530, PMID 37504410.

18. Odeniyi MA, Okumah VC, Adebayo-Tayo BC, Odeniyi OA. Green synthesis and cream formulations of silver nanoparticles of Nauclea latifolia (African peach) fruit extracts and evaluation of antimicrobial and antioxidant activities. Sustain Chem Pharm. 2020 Mar 1;15:100197. doi: 10.1016/j.scp.2019.100197.

19. Al-Ansari MM, Al-Dahmash ND, Ranjitsingh AJ. Synthesis of silver nanoparticles using gum arabic: evaluation of its inhibitory action on Streptococcus mutans causing dental caries and endocarditis. J Infect Public Health. 2021 Mar 1;14(3):324-30. doi: 10.1016/j.jiph.2020.12.016, PMID 33618277.

20. Mallineni SK, Sakhamuri S, Kotha SL, AlAsmari AR, AlJefri GH, Almotawah FN. Silver nanoparticles in dental applications: a descriptive review. Bioengineering (Basel). 2023 Mar 5;10(3):327. doi: 10.3390/bioengineering10030327, PMID 36978718.

21. Pandey AK, Harit AK, Sonekar K. Quantitative estimation of secondary metabolites, in vitro antioxidant, anti-inflammatory, and anti-sickling activity of leaf of Ficus virens Aiton. Int J Ayur Med. 2025;16(1):52-63. doi: 10.47552/ijam.v16i1.5317.

22. Saini Y, Kaushik K, Choudhary M, Bamrah PK, Choudhary N, Goyal A. Gastroprotective effect of ethanol extract of Ficus virens Aiton bark in ethanol induced in vivo ulcer model and exploring mechanism via molecular docking studies. Nutrire. 2025 Jun 2;50(1):42. doi: 10.1186/s41110-025-00341-7.

23. Ahmed S, Saifullah, Ahmad M, Swami BL, Ikram S. Green synthesis of silver nanoparticles using Azadirachta indica aqueous leaf extract. Journal of Radiation Research and Applied Sciences. 2016;9(1):1-7. doi: 10.1016/j.jrras.2015.06.006.

24. Saxena A, Tripathi RM, Zafar F, Singh P. Green synthesis of silver nanoparticles using aqueous solution of Ficus benghalensis leaf extract and characterization of their antibacterial activity. Mater Lett. 2012 Jan 15;67(1):91-4. doi: 10.1016/j.matlet.2011.09.038. matlet.2011.09.038.

25. Mihailovic V, Sreckovic N, Nedic ZP, Dimitrijevic S, Matic M, Obradovic A. Green synthesis of silver nanoparticles using Salvia verticillata and Filipendula ulmaria extracts: optimization of synthesis, biological activities, and catalytic properties. Molecules. 2023 Jan 13;28(2):808. doi: 10.3390/molecules28020808, PMID 36677866.

26. Singh C, Rao K, Yadav N, Bansal N, Vashist Y, Kumari S. A review: drug excipient Iincompatiblity by ftir spectroscopy. Curr Pharm Anal. 2023 Jun 1;19(5):371-8. doi: 10.2174/1573412919666230228102158.

27. Chadha R, Bhandari S. Drug-excipient compatibility screening – role of thermoanalytical and spectroscopic techniques. J Pharm Biomed Anal. 2014 Jan 18;87:82-97. doi: 10.1016/j.jpba.2013.06.016, PMID 23845418.

28. Rojek B, Wesolowski M. FTIR and TG analyses coupled with factor analysis in a compatibility study of acetazolamide with excipients. Spectrochim Acta A Mol Biomol Spectrosc. 2019 Feb 5;208:285-93. doi: 10.1016/j.saa.2018.10.020, PMID 30340208.

29. Aminu N, Chan SY, Mumuni MA, Umar NM, Tanko N, Zauro SA. Physicochemical compatibility studies of triclosan and flurbiprofen with excipients of pharmaceutical formulation using binary, ternary, and multi-combination approach. Futur J Pharm Sci. 2021 Jul 22;7(1):148. doi: 10.1186/s43094-021-00302-7.

30. Chen XX, Wu XB, Chai WM, Feng HL, Shi Y, Zhou HT. Optimization of extraction of phenolics from leaves of Ficus virens. J Zhejiang Univ Sci B. 2013 Oct;14(10):903-15. doi: 10.1631/jzus.B1200365. PMID 24101207.

31. Mahmoud MR, Mahgoub SM, Abdelazeem R, Abdelsatar MM, Allam AA, Alfassam HE. RP-HPLC method development and validation for the quantification of prednisolone and salbutamol with their simultaneous removal from water using modified clay–activated carbon adsorbents. RSC Adv. 2025;15(11):8675-95. doi: 10.1039/D5RA00324E, PMID 40114727.

32. Kaur SU, Kaur TA, Kaur GU, Verma SH. Development and validation of UV-spectrophotometric method for estimation of hydroquinone in bulk, marketed cream and prepared NLC formulation. Int J App Pharm. 2017 Sep;9(5):102-8. doi: 10.22159/ijap.2017v9i5.20467.

33. Makeen HA, Albratty M. Sesamol loaded silver nanoparticles gel engineered for wound healing via topical delivery: optimization in vitro and ex vivo evaluation. Curr Pharm Des. 2024 Dec;30(40):3175-89. doi: 10.2174/0113816128306956240801052553, PMID 39192646.

34. Aldakheel FM, Mohsen D, El Sayed MM, Fagir MH, El Dein DK. Green synthesized silver nanoparticles loaded in polysaccharide hydrogel applied to chronic wound healing in mice models. Gels. 2023 Aug 11;9(8):646. doi: 10.3390/gels9080646, PMID 37623101.

35. Wu X, Chen HW, Zhao ZY, Li L, Song C, Xiong J. Carbopol 940-based hydrogels loading synergistic combination of quercetin and luteolin from the herb Euphorbia humifusa to promote Staphylococcus aureus infected wound healing. RSC Med Chem. 2024;15(2):553-60. doi: 10.1039/D3MD00611E, PMID 38389873.

36. Budarapu D, Mohan Kumar U, Sravanthi P. Design, formulation and in vitro evaluation of ketoconazole microsponges by quasi-emulsion solvent diffusion method. J Drug Delivery Ther. 2025;15(7):19-24. doi: 10.22270/jddt.v15i7.7244.

37. Hassan H, Adam SK, Alias E, Meor Mohd Affandi MM, Shamsuddin AF, Basir R. Central composite design for formulation and optimization of solid lipid nanoparticles to enhance oral bioavailability of acyclovir. Molecules. 2021 Sep 7;26(18):5432. doi: 10.3390/molecules26185432, PMID 34576904.

38. Singh AP, Kashaw SK, Soni V. Design, optimisation and in vivo evaluation of tazarotene loaded emulgel formulation for the treatment of acne. J Drug Target. 2025 Aug 10:1-9. doi: 10.1080/1061186X.2025.2546489.

39. Desu PK, Karmakar B, Kondi V, Tiwari ON, Halder G. Optimizing formulation of green tea extract-loaded chitosan nanogel. Biomass Conv Bioref. 2024 Feb;14(3):3209-22. doi: 10.1007/s13399-022-02453-w.

40. Vandana D, Shweta Pawar. Formulation and evaluation of topical herbal gel containing inclusion complex of curcumin. Asian J Pharm Clin Res. 2019:196-201. doi: 10.22159/ajpcr.2019.v12i9.34053.

41. Alam MS, Algahtani MS, Ahmad J, Kohli K, Shafiq-un-Nabi S, Warsi MH. Formulation design and evaluation of aceclofenac nanogel for topical application. Ther Deliv. 2020 Dec 1;11(12):767-78. doi: 10.4155/tde-2020-0076, PMID 33225842.

42. Alam MS, Sultana N, Rashid MA, Alhamhoom Y, Ali A, Waheed A. Quality by design-optimized glycerosome-enabled nanosunscreen gel of rutin hydrate. Gels. 2023 Sep 15;9(9):752. doi: 10.3390/gels9090752, PMID 37754433.

43. Mhetre RL, Kagade AD, Dhole SN. Nanoemulgel for treatment of topical fungal infection: formulation and optimization using box–behnken design. BioNano Science. 2025 Sep;15(3):1-4. doi: 10.1007/s12668-025-02121-z.

44. Avinash S, Gowda DV, Suresh J, Ram AS, Srivastava A, Osmani RM. Formulation and evaluation of topical gel using Eupatorium glandulosum Michx. for wound healing activity. Scholars Res Libr. 2016;8(8):255-66.

45. Lv Y, He H, Qi J, Lu Y, Zhao W, Dong X. Visual validation of the measurement of entrapment efficiency of drug nanocarriers. Int J Pharm. 2018 Aug 25;547(1-2):395-403. doi: 10.1016/j.ijpharm.2018.06.025, PMID 29894757.

46. Sodimalla T, Yalavarthi N. Biosynthesis of silver nanoparticles from Pseudomonas fluorescens and their antifungal activity against Aspergillus niger and Fusarium udum. Ann Appl Biol. 2022 Sep;181(2):235-45. doi: 10.1111/aab.12761.

47. Pandey S, Paul S, Jangde KK, Mishra DK. Development of sertaconazole loaded nanoemulgel using quality by design approach for enhanced antifungal drug delivery. J Pharm Innov. 2025 Oct;20(5):1-20. doi: 10.1007/s12247-025-10075-8.

48. Afreen U, Fahelelbom KM, Shah SN, Ashames A, Almas U, Khan SA. Formulation and evaluation of niosomes-based chlorpheniramine gel for the treatment of mild to moderate skin allergy. J Exp Nanosci. 2022 Dec 31;17(1):467-95. doi: 10.1080/17458080.2022.2094915.

49. Bhattacharya SA, Paul BI, Biswas GR. Development and evaluation of hydrogel of an anti-fungal drug. Int J Pharm Pharm Sci. 2023;15(10):29-33. doi: 10.22159/ijpps.2023v15i10.48728.

50. Jayachandran P, Ilango S, Suseela V, Nirmaladevi R, Shaik MR, Khan M. Green synthesized silver nanoparticle-loaded liposome-based nanoarchitectonics for cancer management: in vitro drug release analysis. Biomedicines. 2023 Jan 14;11(1):217. doi: 10.3390/biomedicines11010217, PMID 36672725.

51. Sadati Behbahani ES, Ghaedi M, Abbaspour M, Rostamizadeh K, Dashtian K. Curcumin loaded nanostructured lipid carriers: in vitro digestion and release studies. Polyhedron. 2019 May 15;164:113-22. doi: 10.1016/j.poly.2019.02.002.

52. Ahmadipour Z, Seyed Dorraji MS, Ashjari HR, Dodangeh F, Rasoulifard MH. Applying in-situ visible photopolymerization for fabrication of electrospun nanofibrous carrier for meloxicam delivery. Sci Rep. 2023 Jun 16;13(1):9741. doi: 10.1038/s41598-023-36893-9, PMID 37328688.

53. Pathan IB, Dwivedi R, Ambekar W. Formulation and evaluation of ketoprofen-loaded chitosan nanogel for pain management: ex vivo and in vivo study. Ars Pharm. 2019 Jun;60(2):101-8. doi: 10.30827/ars.v60i2.8563.

54. Mohammed GM, Hawar SN. Green biosynthesis of silver nanoparticles from Moringa oleifera leaves and its antimicrobial and cytotoxicity activities. Int J Biomater. 2022;2022(1):4136641. doi: 10.1155/2022/4136641, PMID 36193175.

55. Kabiru HD, Ahmad KB, Bello NM, Paul SO. Formulation and evaluation of in vitro antioxidant and antimicrobial activities of herbal hydrogel loaded with Moringa oleifera leaf extract. Sci World J. 2023 Apr 23;18(1):101-5. doi: 10.1371/journal.pone.0326858.

56. Martinez Higuera A, Rodriguez Beas C, Villalobos Noriega JM, Arizmendi Grijalva A, Ochoa Sanchez C, Larios Rodriguez E. Hydrogel with silver nanoparticles synthesized by Mimosa tenuiflora for second-degree burns treatment. Sci Rep. 2021 May 28;11(1):11312. doi: 10.1038/s41598-021-90763-w, PMID 34050228.

57. Aminu N, Alfred-Ugbenbo D, Moradeke O, Audu Mumuni M, Muhammad Umar N, Tanko N. Nanogel drug delivery system loaded with Azadirachta indica A. Juss. (Neem) for potential treatment of wound infection: development and characterization. Beni-Suef Univ J Basic Appl Sci. 2025 Jun 21;14(1):67. doi: 10.1186/s43088-025-00655-5.

58. Kumbhar S, Khairate R, Bhatia M, Choudhari P, Gaikwad V. Evaluation of curcumin-loaded chitosan nanoparticles for wound healing activity. ADMET DMPK. 2023 Oct 19;11(4):601-13. doi: 10.5599/admet.1897, PMID 37937244.

59. Chethan HV, Mohapatra D, SAHU A, Hemalatha S. Formulation development and evaluation of hydrogel containing silver nanoparticles with Withania coagulans aqueous extract. Indian J Pharm Sci. 2023 Jul 1;85(4). doi: 10.36468/pharmaceutical-sciences.1165.

60. Ragab A, El-Badry N, Tamer N, Naas A, Hamdy A, Tawakey SH. Biodegradable chitosan/PVA-based hydrogel incorporating green synthesized silver nanoparticles for wound healing applications. BMC Chem. 2025 Dec;19(1):190. doi: 10.1186/s13065-025-01564-5, PMID 40611305.

61. Din IU, Ajaj R, Rauf A, Ahmad Z, Muhammad N, Ali S. Ficus benghalensis extract mediated green synthesis of silver nanoparticles, its optimization, characterization, computational studies, and its in vitro and in vivo biological potential. PLOS One. 2025 Jul 1;20(7):e0326858. doi: 10.1371/journal.pone.0326858, PMID 40591582.

62. Buggana A, Bandari K, Golla N, Golla N, Abd-Elsalam KA. Leaf-mediated green synthesis of silver nanoparticles from Azadirachta indica and Ficus religiosa: characterization and bioactive properties. Egypt J Agric Res. 2024 Sep 1;102(3):392-406. doi: 10.21608/ejar.2024.285666.1541.

63. Sood R, Chopra DS. Optimization of reaction conditions to fabricate Ocimum sanctum synthesized silver nanoparticles and its application to nano-gel systems for burn wounds. Mater Sci Eng C Mater Biol Appl. 2018 Nov 1;92:575-89. doi: 10.1016/j.msec.2018.06.070, PMID 30184784.

64. Fatima F, Aldawsari MF, Ahmed MM, Anwer MK, Naz M, Ansari MJ. Green synthesized silver nanoparticles using Tridax procumbens for topical application: excision wound model and histopathological studies. Pharmaceutics. 2021 Oct 21;13(11):1754. doi: 10.3390/pharmaceutics13111754, PMID 34834169.

65. Rajurkar A, Gogri D, Jamdade N, Pathak A. Green synthesis of silver nanoparticles: their characterization, antimicrobial, antioxidant activity and nanogel formulation. Nano Biomed Eng. 2023 Mar 1;15(1):42-50. doi: 10.26599/NBE.2023.9290006.

Published

07-11-2025

How to Cite

AGGARWAL, D., SAROHA, K., CHOUDHARY, M., & KAUSHIK, K. (2025). DEVELOPMENT AND EVALUATION OF SILVER NANOPARTICLES-LOADED PHYTOGEL OF HYDROALCOHOLIC EXTRACT OF FICUS VIRENS BARK: FORMULATION, OPTIMIZATION, AND ANTIMICROBIAL EFFICACY. International Journal of Applied Pharmaceutics, 17(6), 436–450. https://doi.org/10.22159/ijap.2025v17i6.56393

Issue

Section

Original Article(s)

Similar Articles

1 2 3 4 5 > >> 

You may also start an advanced similarity search for this article.