Alginate–Basil Seed Hydrogel Films for Sustained Topical Delivery of Silver Sulfadiazine

Abstract

This study developed and evaluated silver sulfadiazine (SSD)-loaded hydrogel films based on sodium alginate (SA) and basil seed mucilage (BSM) for controlled topical delivery. Films were formulated by varying SA (800–1000 mg) and BSM (50–200 mg) with calcium chloride (CaCl2) (5–15%) as the crosslinker and propylene glycol (15% w/w) as a plasticizer. The optimized film (900 mg SA, 100 mg BSM, 10% CaCl2, 30 min) was selected for its superior integrity and swelling. Attenuated Total Reflectance–Fourier Transform Infrared Spectroscopy (ATR–FTIR), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), and X-ray Diffraction (XRD) confirmed SSD compatibility and uniform polymer dispersion. The optimized film exhibited high swelling (~38 g/g), moderate thickness (~609 μm), excellent flexibility (~252 folds), optimum tensile strength (0.454 kg/cm2) and good surface wettability (~48° contact angle), reflecting balanced hydrophilicity and mechanical strength. In vitro release followed Fickian diffusion (Korsmeyer–Peppas n < 0.45), while additional evaluations confirmed appropriate water vapor transmission, microbial barrier properties, and hemocompatibility (< 5% hemolysis), supporting its biocompatibility. Overall, SA–BSM hydrogel films show strong potential as wound dressings, offering a stable, biocompatible matrix for sustained SSD delivery. However, as the study was limited to in vitro evaluations, further in vivo, stability, wound healing, and mechanical studies are warranted.

Keywords

• Sodium alginate
• Basil seed mucilage
• Hydrogel films
• Silver sulfadiazine
• Topical delivery

Supporting Institution

Adarsh College of Pharmacy, Vita

Project Number

Nil

Ethical Statement

Not required

Thanks

The authors are thankful to Adv. Vaibhav (Dada) Patil, President of the Loknete Hon. Hanmantrao Patil Charitable Trust, Vita, for providing the necessary facilities to carry out the research work. Shivaji University, Kolhapur; Krishna Vishwa Vidyapeeth, Karad; and Sadguru Gadage Maharaj College, Karad are acknowledged for their assistance with analytical work.

References

1. 1. Mozaffari E, Tanhaei B, Khajenoori M, Movaghar Khoshkho S. Unveiling the swelling behavior of κ-carrageenan hydrogels: Influence of composition and physiological environment on drug delivery potential. J Ind Eng Chem. 2025; 141: 217–27. https://doi.org/10.1016/j.jiec.2024.06.032.
2. 2. Sharmin N, Sone I, Walsh JL, Sivertsvik M, Fernández EN. Effect of citric acid and plasma activated water on the functional properties of sodium alginate for potential food packaging applications. Food Packag Shelf Life. 2021; 29: 100733. https://doi.org/10.1016/j.fpsl.2021.100733.
3. 3. He C, Bi S, Zhang L, Gu J, Yan B. An antioxidative sodium alginate hybrid hydrogel with NIR-controlled NO releasing for diabetic wound healing via reduced inflammation and enhanced angiogenesis. Carbohydr Polym. 2025; 366: 123913. https://doi.org/10.1016/j.carbpol.2025.123913.
4. 4. Kapoor DU, Pareek A, Sharma S, Prajapati BG, Thanawuth K, Sriamornsak P. Alginate gels: Chemistry, gelation mechanisms, and therapeutic applications with a focus on GERD treatment. Int J Pharm. 2025; 675: 125570. https://doi.org/10.1016/j.ijpharm.2025.125570.
5. 5. Wang H, Liu J, Fan X, Ren J, Liu Q, Kong B. Fabrication, characterisation, and application of green crosslinked sodium alginate hydrogel films by natural crab-shell powders to achieve drug sustained release. LWT 2022; 171: 114147. https://doi.org/10.1016/j.lwt.2022.114147.
6. 6. Bustos-Terrones YA. A Review of the Strategic Use of Sodium Alginate Polymer in the Immobilization of Microorganisms for Water Recycling. Polymers (Basel). 2024; 16: 788. https://doi.org/10.3390/polym16060788.
7. 7. Shah Bukhary SKH, Choudhary FK, Iqbal DN, Ali Z, Sadiqa A, Latif S, et al. Development and characterization of a biodegradable film based on guar gum-gelatin sodium alginate for a sustainable environment. RSC Adv. 2024; 14: 19349–61. https://doi.org/10.1039/D4RA03985H.
8. 8. Phonrat A, Subyai N, Prachayawarakorn J. Alternative Polysaccharide Wound Dressing from Heat-Moisture Starch/Basil Seed ( O. Basilicum L.) Mucilage with Incorporated Glycolic Acid Antimicrobial Agent. J Macromol Sci Part B. 2025; 64: 845–66. https://doi.org/10.1080/00222348.2024.2367340.

9. 9. Ullah S, Hashmi M, Kharaghani D, Khan MQ, Saito Y, Yamamoto T, et al. Antibacterial properties of in situ and surface functionalized impregnation of silver sulfadiazine in polyacrylonitrile nanofiber mats. Int J Nanomedicine. 2019; 14: 2693–703. https://doi.org/10.2147/IJN.S197665.
10. 10. Yari K, Akbari I, Yazdi SAV. Development and evaluation of sodium alginate-basil seeds mucilage beads as a suitable carrier for controlled release of metformin. Int J Biol Macromol. 2020; 159: 1–10. https://doi.org/10.1016/j.ijbiomac.2020.04.111.
11. 11. Srikhao N, Chirochrapas K, Kwansanei N, Kasemsiri P, Ounkaew A, Okhawilai M, et al. Multi-Responsive Optimization of Novel pH-Sensitive Hydrogel Beads Based on Basil Seed Mucilage, Alginate, and Magnetic Particles. Gels. 2022; 8: 274. https://doi.org/10.3390/gels8050274.
12. 12. Su C, Li D, Wang L. From micropores to mechanical strength: Fabrication and characterization of edible corn starch-sodium alginate double network hydrogels with Ca2+ cross-linking. Food Chem. 2025; 467: 142276. https://doi.org/10.1016/j.foodchem.2024.142276.
13. 13. Saranya T, Manoj K. Formulation, evaluation and optimization of novel silver sulfadiazine loaded film forming hydrogel for burns. Hygeia J Drugs Med 2016; 8: 1–10. https://doi.org/10.15254/H.J.D.Med.8.2016.156.
14. 14. Guan L, Ma Y, Yu F, Jiang X, Jiang P, Zhang Y, et al. The recent progress in the research of extraction and functional applications of basil seed gum. Heliyon. 2023; 9: e19302. https://doi.org/10.1016/j.heliyon.2023.e19302.
15. 15. Salunkhe NH, Mali KK, Sidwadkar PH, Pareek KM, Aundhakar AS. Synthesis and characterization of citric acid crosslinked garden cress seeds mucilage hydrogel for controlled drug release. J Drug Deliv Sci Technol. 2025;112:107270. https://doi.org/10.1016/j.jddst.2025.107270.
16. 16. Ghorpade VS, Mali KK, Dias RJ, Dhawale SC, Digole RR, Gandhi JM, et al. Citric acid crosslinked hydroxyethyl tamarind gum-based hydrogel films: A promising biomaterial for drug delivery. Int J Biol Macromol. 2024; 282: 137127. https://doi.org/10.1016/j.ijbiomac.2024.137127.
17. 17. Pargaonkar SS, Ghorpade VS, Mali KK, Dias RJ, Havaldar VD, Kadam VJ. Hydrogel Films of Citric Acid Cross-linked Hydroxypropyl Methylcellulose/Methylcellulose for Hydrophilic Drug Delivery. Indian J Pharm Educ Res. 2023; 57: 718–27. https://doi.org/10.5530/ijper.57.3.87.
18. 18. Mali KK, Dhawale SC, Dias RJ, Ghorpade VS, Dhane NS. Development of vancomycin-loaded polysaccharide-based hydrogel wound dressings: In vitro and in Vivo evaluation. Asian J Pharm. 2018; 12: 94–105.
19. 19. Lan W, He L, Liu Y. Preparation and Properties of Sodium Carboxymethyl Cellulose/Sodium Alginate/Chitosan Composite Film. Coatings. 2018; 8: 291. https://doi.org/10.3390/coatings8080291.
20. 20. Singh B, Sharma S, Dhiman A. Design of antibiotic containing hydrogel wound dressings: Biomedical properties and histological study of wound healing. Int J Pharm. 2013; 457: 82–91. https://doi.org/10.1016/j.ijpharm.2013.09.028.
21. 21. Jadach B, Misek M, Ferlak J. Comparison of Hydroxypropyl Methylcellulose and Alginate Gel Films with Meloxicam as Fast Orodispersible Drug Delivery. Gels. 2023; 9: 687. https://doi.org/10.3390/gels9090687.
22. 22. Mastiholimath VS, Valerie CTW, Mannur VS, Dandagi PM, Gadad AP, Khanal P. Formulation and evaluation of solid lipid nanoparticle containing silver sulfadiazine for second and third degree burn wounds and its suitable analytical method development and validation. Indian J Pharm Educ Res. 2020; 54: 31–45. https://doi.org/10.5530/ijper.54.1.5.
23. 23. Giz AS, Berberoglu M, Bener S, Aydelik-Ayazoglu S, Bayraktar H, Alaca BE, et al. A detailed investigation of the effect of calcium crosslinking and glycerol plasticizing on the physical properties of alginate films. Int J Biol Macromol. 2020; 148: 49–55. https://doi.org/10.1016/j.ijbiomac.2020.01.103.
24. 24. Shao W, Liu H, Liu X, Wang S, Wu J, Zhang R, et al. Development of silver sulfadiazine loaded bacterial cellulose/sodium alginate composite films with enhanced antibacterial property. Carbohydr Polym. 2015; 132: 351–8. https://doi.org/10.1016/j.carbpol.2015.06.057.
25. 25. Mali KK, Dhawale SC, Dias RJ. Synthesis and characterization of hydrogel films of carboxymethyl tamarind gum using citric acid. Int J Biol Macromol. 2017; 105: 463–70. https://doi.org/10.1016/j.ijbiomac.2017.07.058.
26. 26. Hosseini MS, Nabid MR. Synthesis of chemically cross-linked hydrogel films based on basil seed (Ocimum basilicum L.) mucilage for wound dressing drug delivery applications. Int J Biol Macromol. 2020; 163: 336–47. https://doi.org/10.1016/j.ijbiomac.2020.06.252.
27. 27. Janik W, Nowotarski M, Ledniowska K, Shyntum DY, Krukiewicz K, Turczyn R, et al. Modulation of physicochemical properties and antimicrobial activity of sodium alginate films through the use of chestnut extract and plasticizers. Sci Rep. 2023; 13: 11530. https://doi.org/10.1038/s41598-023-38794-3.
28. 28. Arafa EG, Gawad OFA, Eldin ZE, Ibrahim MM, Abd-Elghafour SA, Osman AHM. Sustainable sodium alginate hydrogels incorporating banana leaf activated carbon and organo-clay for enhanced dye removal. Sci Rep. 2025; 15: 16197. https://doi.org/10.1038/s41598-025-99343-8.
29. 29. Alam MN, Christopher LP. A novel, cost-effective and eco-friendly method for preparation of textile fibers from cellulosic pulps. Carbohydr Polym, 2017; 173: 253–8. https://doi.org/10.1016/j.carbpol.2017.06.005.
30. 30. Zhang H, Gao X, Chen K, Li H, Peng L. Thermo-sensitive and swelling properties of cellouronic acid sodium/poly (acrylamide-co-diallyldimethylammonium chloride) semi-IPN. Carbohydr Polym. 2018; 181: 450–9. https://doi.org/10.1016/j.carbpol.2017.10.093.
31. 31. Peter Z. Order in cellulosics: Historical review of crystal structure research on cellulose. Carbohydr Polym. 2021; 254: 117417. https://doi.org/10.1016/j.carbpol.2020.117417.
32. 32. Saad MA, Sadik ER, Eldakiky BM, Moustafa H, Fadl E, He Z, et al. Synthesis and characterization of an innovative sodium alginate/polyvinyl alcohol bioartificial hydrogel for forward-osmosis desalination. Sci Rep. 2024; 14: 8225. https://doi.org/10.1038/s41598-024-58533-6.
33. 33. Samiee Paghaleh E, Kolvari E, Seidi F, Dashtian K. Eco-friendly and sustainable basil seed hydrogel-loaded copper hydroxide-based catalyst for the synthesis of propargylamines and tetrazoles. Nanoscale Adv. 2024; 6: 960–72. https://doi.org/10.1039/D3NA01085F.
34. 34. Bult A, Plug CM. Silver Sulfadiazine. Anal. Profiles Drug Subst. Excipients, vol. 13, 1984, p. 553–71. https://doi.org/10.1016/S0099-5428(08)60202-6.
35. 35. Hashemi Gahruie H, Eskandari MH, Sadeghi R, Hosseini SMH. Atmospheric Pressure Cold Plasma Modification of Basil Seed Gum for Fabrication of Edible Film Incorporated with Nanophytosomes of Vitamin D3 and Tannic Acid. Foods. 2022; 12: 71. https://doi.org/10.3390/foods12010071.
36. 36. Aswathy SH, NarendraKumar U, Manjubala I. Physicochemical Properties of Cellulose-Based Hydrogel for Biomedical Applications. Polymers (Basel). 2022; 14: 4669. https://doi.org/10.3390/polym14214669.
37. 37. Kumar A, Pathak M. Formulation, Evaluation & in - Vivo Study of Topical Emul Gel Loaded With Silver Sulfadiazine for Wound. African J Biol Sci. 2024; 6: 3321–47. https://doi.org/10.33472/AFJBS.6.9.2024.3320-3366.
38. 38. Ghumman SA, Noreen S, Hameed H, Elsherif MA, Shabbir R, Rana M, et al. Synthesis of pH-Sensitive Cross-Linked Basil Seed Gum/Acrylic Acid Hydrogels by Free Radical Copolymerization Technique for Sustained Delivery of Captopril. Gels. 2022; 8: 291. https://doi.org/10.3390/gels8050291.
39. 39. Pereira R, Carvalho A, Vaz DC, Gil MH, Mendes A, Bártolo P. Development of novel alginate based hydrogel films for wound healing applications. Int J Biol Macromol. 2013; 52: 221–30. https://doi.org/10.1016/j.ijbiomac.2012.09.031.
40. 40. Kalam MA. The potential application of hyaluronic acid coated chitosan nanoparticles in ocular delivery of dexamethasone. Int J Biol Macromol. 2016; 89: 559–68. https://doi.org/10.1016/j.ijbiomac.2016.05.016.
41. 41. Dong Z, Wang Q, Du Y. Alginate/gelatin blend films and their properties for drug controlled release. J Memb Sci. 2006; 280: 37–44. https://doi.org/10.1016/j.memsci.2006.01.002.
42. 42. Chalitangkoon J, Wongkittisin M, Monvisade P. Silver loaded hydroxyethylacryl chitosan/sodium alginate hydrogel films for controlled drug release wound dressings. Int J Biol Macromol. 2020; 159: 194–203. https://doi.org/10.1016/j.ijbiomac.2020.05.061.
43. 43. Rezvanian M, Ahmad N, Cairul M, Mohd I, Ng S. International Journal of Biological Macromolecules Optimization, characterization, and in vitro assessment of alginate-pectin ionic cross-linked hydrogel film for wound dressing applications. Int J Biol Macromol. 2017; 97: 131–40. https://doi.org/10.1016/j.ijbiomac.2016.12.079.
44. 44. Park SY, Kim W-J, Choi JB, Kim S. Physical and mechanical properties of alginate-based hydrogel film as carrier for release of acetylthiocholine. Int J Precis Eng Manuf 2018; 19: 129–35. https://doi.org/10.1007/s12541-018-0015-1.
45. 45. Li X, Al-Assaf S, Fang Y, Phillips GO. Competitive adsorption between sugar beet pectin (SBP) and hydroxypropyl methylcellulose (HPMC) at the oil/water interface. Carbohydr Polym. 2013; 91: 573–80. https://doi.org/10.1016/j.carbpol.2012.08.075.
46. 46. bt Ibrahim SF, Mohd Azam NAN, Mat Amin KA. Sodium alginate film: the effect of crosslinker on physical and mechanical properties. IOP Conf Ser Mater Sci Eng. 2019; 509: 012063. https://doi.org/10.1088/1757-899X/509/1/012063.
47. 47. Tantiwatcharothai S, Prachayawarakorn J. Characterization of an antibacterial wound dressing from basil seed (Ocimum basilicum L.) mucilage-ZnO nanocomposite. Int J Biol Macromol. 2019; 135: 133–40. https://doi.org/10.1016/j.ijbiomac.2019.05.118.
48. 48. Goh CH, Heng PWS, Chan LW. Alginates as a useful natural polymer for microencapsulation and therapeutic applications. Carbohydr Polym. 2012; 88: 1–12. https://doi.org/10.1016/j.carbpol.2011.11.012.
49. 49. Mali KK, Havaldar VD, Salunkhe NH, Varude OS, Mahajan NS, Dias RJ. Development of carboxymethyl tamarind gum-based composite hydrogel films for wound dressing applications. Eur Pharm J. 2025; 6786:1–14. https://doi.org/10.2478/afpuc-2025-0010.