QBD-DRIVEN DESIGN OF CALENDULA ESSENTIAL OIL NANOSPONGE TOPICAL GEL FOR ENHANCED ANTIBACTERIAL EFFICACY
DOI:
https://doi.org/10.22159/ijap.2025v17i5.54461Keywords:
Calendula essential oil, Nanosponge, Box-behnken design, Antibacterial activityAbstract
Objective: The objective of this research was to design and optimize calendula essential oil-loaded nanosponges (CEO-NS) using a quality-by-design (QbD) strategy and formulate them into a topical gel to improve antibacterial activity and obtain controlled drug release.
Methods: CEO-NS were prepared using the emulsion solvent diffusion technique, using ethyl cellulose (EC) as the polymer and polyvinyl alcohol (PVA) as the stabilizer. A box-behnken design (BBD) was utilized for the optimization of formulation variables. NS were characterized by particle size, polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), Fourier-transform infra-red spectroscopy (FTIR), and scanning electron microscopy (SEM). The chosen optimized formulations (NS18, NS19, NS20) were loaded into gels (G1, G2, G3) and tested for viscosity, pH, spreadability, homogeneity, in vitro drug release, and antibacterial activity.
Results: Among the formulations tested, NS18 was considered an ideal formulation with a particle size of 268.7 nm, a PDI of 0.421, ZP of-20.98 mV, and the predicted desirability of formulation NS18 was 1, while the actual experimental desirability was 0.9157, indicating excellent agreement and near-optimal performance. This was an indicator of good colloidal stability. The percentage EE was between 78±1.6 and 92±2.2. SEM showed spherical porous morphology, and FTIR showed the absence of significant drug-excipient interactions. The G1 showed optimum physicochemical characteristics (viscosity: 3454.12–3678.23 cps; spreadability: 40.37–66.77 g/cm/sec; pH: 5.2–5.7), The controlled drug release observed in G1 gel is a sustained release, where the drug is released at a steady rate over 8 h. It follows the Hixson-Crowell model and has better antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) than pure CEO.
Conclusion: The topical gel (G1) controlled the release of the drug with improved antibacterial efficacy, making it a promising formulation for topical antibacterial therapy.
References
1. Poolman JT, Anderson AS. Escherichia coli and Staphylococcus aureus: leading bacterial pathogens of healthcare associated infections and bacteremia in older age populations. Expert Rev Vaccines. 2018;17(7):607-18. doi: 10.1080/14760584.2018.1488590, PMID 29902092.
2. Haq K, Figgitt M, Lee D. Phage therapy against antibiotic resistant and multidrug-resistant infections involving nonhealing wounds and prosthetic joint infections associated with biofilms: a mini-review. Can J Infect Dis Med Microbiol. 2024;2024(1):6252415. doi: 10.1155/2024/6252415, PMID 39545100.
3. Hatem H, Abdelaziz R. Revolutionizing the fight against multidrug resistant bacteria: phage and phage products as the leading armament in future. J Adv Vet Res. 2024;14(5):913-6.
4. Zelellw DA, Dessie G, Worku Mengesha E, Balew Shiferaw M, Mela Merhaba M, Emishaw S. A systemic review and meta-analysis of the leading pathogens causing neonatal sepsis in developing countries. BioMed Res Int. 2021;2021(1):6626983. doi: 10.1155/2021/6626983, PMID 34195273.
5. Shahane K, Kshirsagar M, Tambe S, Jain D, Rout S, Ferreira MK. An updated review on the multifaceted therapeutic potential of Calendula officinalis L. Pharmaceuticals (Basel). 2023;16(4):611. doi: 10.3390/ph16040611, PMID 37111369.
6. Chaleshtori SH, Kachoie MA, Pirbalouti AG. Phytochemical analysis and antibacterial effects of Calendula officinalis essential oil. Biosci Biotech Res Comm. 2016;9(3):517-22. doi: 10.21786/bbrc/9.3/26.
7. Hamad MN, Mohammed HJ, Merdaw MA. Antibacterial activity of Calendula officinalis flowers in vitro. IHJPAS. 2011;24(3). doi: 10.30526/24.3.735.
8. Basch E, Bent S, Foppa I, Haskmi S, Kroll D, Mele M. Marigold (Calendula officinalis L.): an evidence based systematic review by the natural standard research collaboration. J Herb Pharmacother. 2006;6(3-4):135-59. doi: 10.1080/j157v06n03_08, PMID 17317655.
9. Sherje AP, Dravyakar BR, Kadam D, Jadhav M. Cyclodextrin based nanosponges: a critical review. Carbohydr Polym. 2017;173(1):37-49. doi: 10.1016/j.carbpol.2017.05.086, PMID 28732878.
10. Shringirishi M, Prajapati SK, Mahor A, Alok S, Yadav P, Verma A. Nanosponges: a potential nanocarrier for novel drug delivery a review. Asian Pac J Trop Dis. 2014 Feb 1;4 Suppl 2:S519-26. doi: 10.1016/S2222-1808(14)60667-8.
11. Shivani S, Kumar Poladi K. Nanosponges novel emerging drug delivery system: a review. Int J Pharm Sci Res. 2015;6(2):529. doi: 10.13040/IJPSR.0975-8232.6.
12. Bhuyan C, Saha D, Rabha B. A brief review on topical gels as drug delivery system. J Pharm Res Int. 2021;33(4):344-57. doi: 10.9734/jpri/2021/v33i47A33020.
13. Ghourab N, Gardouh Ahmed, Gad S, Moustafa Y. Nanosponge as a drug delivery system. Rec Pharm Biomed Sci. 2020;4(1):17-31.
14. Ahsan Hafiz M, Abbas N, Bukhari NI. Quality by design approach for formulation development and evaluation of carboplatin-loaded ethylcellulose nanosponges. Int J Polym Mater Polym Biomater. 2022;71(13):1012-24. doi: 10.1080/00914037.2021.1933978.
15. Vamshidhar Reddy D, Sambashiva Rao A. Development and evaluation of nanosponges based controlled release tapentadol tablets by box-behnken design. Volatiles Essent Oils. 2021;8(6):5000.
16. Abbas N, Parveen K, Hussain A, Latif S, Uz Zaman SU, Shah PA. Nanosponge-based hydrogel preparation of fluconazole for improved topical delivery. Trop J Pharm Res. 2019 Feb 1;18(2):215-22. doi: 10.4314/tjpr.v18i2.1.
17. Burad S, Markad K, Kulkarni N, Dhole S. Assessment and outcome on preparations characterization of topical targeted nanosponge based drug delivery critical review. Asian Journal of Pharmaceutical and Clinical Research. 2023;16(5):19-26. doi: 10.22159/ajpcr.2023v16i5.46809.
18. Ghareb M Soliman, Shaaban K Osman, Ahmed M Hamdan. Preparation and evaluation of anthralin biodegradable nanoparticles as a potential delivery system for the treatment of psoriasis. International Journal of Pharmacy and Pharmaceutical Sciences. 2015;7(12):36-40.
19. Kumar S, Prasad M, Rao R. Topical delivery of clobetasol propionate loaded nanosponge hydrogel for effective treatment of psoriasis: formulation, physicochemical characterization antipsoriatic potential and biochemical estimation. Mater Sci Eng C Mater Biol Appl. 2021 Feb 1;119:111605. doi: 10.1016/j.msec.2020.111605, PMID 33321649.
20. Gokul M, Umarani G, Esakki A. Green synthesis and characterization of isolated flavonoid mediated copper nanoparticles by using Thespesia populnea leaf extract and its evaluation of anti-oxidant and anti-cancer activity. Int J Chem Res. 2022;6(1):15-32. doi: 10.22159/ijcr.2022v6i1.197.
21. Aldawsari HM, Badr Eldin SM, Labib GS, El Kamel AH. Design and formulation of a topical hydrogel integrating lemongrass loaded nanosponges with an enhanced antifungal effect: in vitro/in vivo evaluation. Int J Nanomedicine. 2015 Jan 29;10:893-902. doi: 10.2147/IJN.S74771, PMID 25673986.
22. Ahmed MM, Fatima F, Anwer MK, Ibnouf EO, Kalam MA, Alshamsan A. Formulation and in vitro evaluation of topical nanosponge based gel containing butenafine for the treatment of fungal skin infection. Saudi Pharm J. 2021;29(5):467-77. doi: 10.1016/j.jsps.2021.04.010, PMID 34135673.
23. Sujitha YS, Muzib YI. Formulation and optimization of quercetin loaded nanosponges topical gel: ex vivo, pharmacodynamic and pharmacokinetic studies. Int J App Pharm. 2019;11(5):156-65. doi: 10.22159/ijap.2019v11i5.32850.
24. Padmini Iriventi NV Gupta. Development and evaluation of nanosponge loaded topical herbal gel of Wrightia tinctoria. International Journal of Applied Pharmaceutics. 2020;12(1):89-95. doi: 10.22159/ijap.2020v12i1.31198.
25. Rupal J, Kaushal J, Mallikarjuna SC, Dipti P. Preparation and evaluation of topical gel of valdecoxib. Int J Pharm Sci Drug Res. 2010;2(1):51-4. doi: 10.25004/IJPSDR.2010.020111.
26. KJ C, Patil MC, Banerjee M, HMA. Preparation and characterization of ficus lacor metallic particles based nanogel for wound healing activity. Int J Curr Pharm Res. 2024;16(1):50-5. doi: 10.22159/ijcpr.2024v16i1.4016.
27. Rathod AG, Raut AR, Jaiswal SR, Awaghate PD, Sayyed SA, Lasure AB. Formulation development and evaluation of topical herbal gel containing Withania somnifera for enhanced antifungal efficacy. Cuestiones de Fisioterapia. 2025;54(2):1193-213. doi: 10.48047/CU.
28. Pasha A, Tomar S. Preparation and evaluation of voriconazole hydrogel using cyclodextrin based nano sponges. Asian Journal of Pharmaceutical and Clinical Research. 2025;18(5):184-92. doi: 10.22159/ajpcr.2025v18i5.54060.
29. Ghurghure S, Pathan M. Preparation and in vitro evaluation of itraconazole loaded nanosponges for topical drug delivery. Indo Am J Pharm Res. 2019;9(4):1999.
30. Subair TK, Mohanan J. Development of nano based film forming gel for prolonged dermal delivery of luliconazole. Int J Pharm Pharm Sci. 2022;14(2):31-41. doi: 10.22159/ijpps.2022v14i2.43253.
31. Bakhrushina EO, Anurova MN, Zavalniy MS, Demina NB, Bardakov AI, Krasnyuk II. Dermatologic gels spreadability measuring methods comparative study. Int J Appl Pharm. 2022;14(1):164-8. doi: 10.22159/ijap.2022v14i1.41267.
32. Kaur M, Nagpal M, Singh M, Singh TG, Aggarwal G, Dhingra GA. Improved antibacterial activity of topical gel based on nanosponge carrier of cinnamon oil. BioImpacts. 2021;11(1):23-31. doi: 10.34172/bi.2021.04, PMID 33469505.
33. Helal DA, Abd El Rhman D, Abdel Halim SA, El Nabarawi MA. Formulation and evaluation of fluconazole topical gel. Int J Pharm Pharm Sci. 2012;4 Suppl 5:176-83.
34. Rafiee Tehrani M, Mehramizi A. In vitro release studies of piroxicam from oil in water creams and hydroalcoholic gel topical formulations. Drug Dev Ind Pharm. 2000;26(4):409-14. doi: 10.1081/ddc-100101247, PMID 10769782.
35. El Gendy AM, Jun HW, Kassem AA. In vitro release studies of flurbiprofen from different topical formulations. Drug Dev Ind Pharm. 2002;28(7):823-31. doi: 10.1081/ddc-120005628, PMID 12236068.
36. Rao BN, Reddy KR, Fathima SR, Preethi P. Design development and evaluation of diltiazem hydrochloride loaded nanosponges for oral delivery. Int J Curr Pharm Sci. 2020;12(5):116-22. doi: 10.22159/ijcpr.2020v12i5.39784.
37. Nalawade TM, Bhat KG, Sogi S. Antimicrobial activity of endodontic medicaments and vehicles using agar well diffusion method on facultative and obligate anaerobes. Int J Clin Pediatr Dent. 2016;9(4):335-41. doi: 10.5005/jp-journals-10005-1388, PMID 28127166.
38. Athanassiadis B, Abbott PV, George N, Walsh LJ. An in vitro study of the antimicrobial activity of some endodontic medicaments and their bases using an agar well diffusion assay. Aust Dent J. 2009;54(2):141-6. doi: 10.1111/j.1834-7819.2009.01107.x, PMID 19473156.
39. Saleem U, Saleem M, Ahmad B, Hussain K, Ahmad M, Bukhari NI. In vitro antimicrobial susceptibility testing of leaves methanol extract and latex of euphorbia helioscopia using agar well diffusion and broth dilution methods. J Anim Plant Sci. 2015;25(1):261-7.
40. Abosede OO, Ezegwu LE. Synthesis and spectroscopic characterization of silver (I) mebendazole complexes. Int J Chem Res. 2022;6(2):1-5. doi: 10.22159/ijcr.2022v6i2.203.
41. Mariana IR. Characterization and antioxidant activity of phytosynthesised silver nanoparticles using Calendula. 2014;62:129-36.
42. Su X, Yang Z, Tan KB, Chen J, Huang J, Li Q. Preparation and characterization of ethyl cellulose film modified with capsaicin. Carbohydr Polym. 2020 Aug 1;241:116259. doi: 10.1016/j.carbpol.2020.116259, PMID 32507184.
43. Sudhamani SR, Prasad MS, Udaya Sankar K. DSC and FTIR studies on gellan and polyvinyl alcohol (PVA) blend films. Food Hydrocoll. 2003;17(3):245-50. doi: 10.1016/S0268-005X(02)00057-7.
Published
How to Cite
Issue
Section
Copyright (c) 2025 R. DHANUSH, K. SUJATHA, C. SOWMYA
This work is licensed under a Creative Commons Attribution 4.0 International License.
