Research Article
BibTex RIS Cite

Year 2025, Volume: 15 Issue: 3, 276 - 286, 31.12.2025
https://doi.org/10.26650/experimed.1768549

Abstract

References

  • 1. Anderson SE, Meade BJ. Potential health effects associated with dermal exposure to occupational chemicals. Environ Health Insights 2014; 8s1: EHI.S15258.
  • 2. D?browska AK, Spano F, Derler S, Adlhart C, Spencer ND, Rossi RM. The relationship between skin function, barrier properties, and body?dependent factors. Skin Res Technol 2018; 24(2): 165-74.
  • 3. Bartold M, Ivanovski S. Biological processes and factors involved in soft and hard tissue healing. Periodontol 2000 2025; 97(1): 16-42.
  • 4. Vicente-da-Silva JV, Pereira JO da SL, do Carmo FA, Patricio BF de C. Skin and wound healing: conventional dosage versus nanobased emulsions forms. ACS Omega 2025; 10(13): 12837-55.
  • 5. Fernandez-Guarino M, Naharro-Rodriguez J, Bacci S. Aberrances of the wound healing process: a review. Cosmetics 2024; 11(6): 209.
  • 6. Saghazadeh S, Rinoldi C, Schot M, Kashaf SS, Sharifi F, Jalilian E, et al. Drug delivery systems and materials for wound healing applications. Adv Drug Deliv Rev 2018; 127: 138-66.
  • 7. Tiwari R, Pathak K. Local Drug Delivery Strategies towards wound healing. Pharmaceutics 2023; 15(2): 634.
  • 8. Liu H, Wang C, Li C, Qin Y, Wang Z, Yang F, et al. A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing. RSC Adv 2018; 8(14): 7533-49.
  • 9. Rathnavelu V, Alitheen NB, Sohila S, Kanagesan S, Ramesh R. Potential role of bromelain in clinical and therapeutic applications. Biomed Rep 2016; 5(3): 283-8.
  • 10. Fathi AN, Sakhaie MH, Babaei S, Babaei S, Slimabad F, Babaei S. Use of bromelain in cutaneous wound healing in streptozocin-induced diabetic rats: an experimental model. J Wound Care 2020; 29(9): 488-95.
  • 11. Bayat S, Rabbani Zabihi A, Amel Farzad S, Movaffagh J, Hashemi E, Arabzadeh S, et al. Evaluation of debridement effects of bromelain-loaded sodium alginate nanoparticles incorporated into chitosan hydrogel in animal models. Iran J Basic Med Sci. 2021 24(10):1404-12.
  • 12. Güven GK, Okur ME, Ayla Ş, Çalışkan G, Al MN, Gülüm L, et al. Boron-doped carbon quantum dots: A biocompatible nanoplatform for targeted cancer theranostics. Int J Pharm 2025; 679: 125745.
  • 13. Camlik G, Bilakaya B, Küpeli Akkol E, Velaro AJ, Wasnik S, Muhar AM, et al. Oral active carbon quantum dots for diabetes. Pharmaceuticals 2024; 17(10): 1395.
  • 14. Camlik G, Bilakaya B, Güven GK, Akkol EK, Degim Z, Sobarzo-Sánchez E, et al. Quantum drugs (Q-Drugs): a new discovery and taboo breaking approach; producing carbon quantum dots from drug molecules. Pharmaceuticals 2025; 18(6): 767.
  • 15. Çağlar Eş, Karaotmarlı Güven G, Üstündağ Okur N. Preparation and characterization of carbopol based hydrogels containing dexpanthenol. J Fac Pharm Ankara 2023; 47(3): 770-83.
  • 16. Nasution H, Harahap H, Dalimunthe NF, Ginting MHS, Jaafar M, Tan OOH, et al. Hydrogel and effects of crosslinking agent on cellulose-based hydrogels: a review. Gels 2022; 8(9): 568.
  • 17. Chamkouri H. A review of hydrogels, their properties and applications in medicine. Am J Biomed Sci Res 2021; 11(6): 485-93.
  • 18. Camlik G, Ozakca I, Bilakaya B, Ozcelikay AT, Velaro AJ, Wasnik S, et al. Development of composite carbon quantum dots-insulin formulation for oral administration. J Drug Deliv Sci Technol 2022; 76: 103833.
  • 19. Alkian I, Sutanto H, Hadiyanto. Quantum yield optimization of carbon dots using response surface methodology and its application as control of Fe3+ ion levels in drinking water. Mater Res Express 2022; 9(1): 015702.
  • 20. Chaudhary H, Kohli K, Amin S, Rathee P, Kumar V. Optimization and formulation design of gels of diclofenac and curcumin for transdermal drug delivery by box-behnken statistical design. J Pharm Sci 2011; 100(2): 580-93.
  • 21. Oliveira MB, Calixto G, Graminha M, Cerecetto H, González M, Chorilli M. Development, characterization, and in vitro biological performance of fluconazole-loaded microemulsions for the topical treatment of cutaneous leishmaniasis. Biomed Res Int 2015; 2015: 396894.
  • 22. Mirani A, Kundaikar H, Velhal S, Patel V, Bandivdekar A, Degani M, et al. Tetrahydrocurcumin-loaded vaginal nanomicrobicide for prophylaxis of HIV/ AIDS: in silico study, formulation development, and in vitro evaluation. Drug Deliv Transl Res 2019; 9(4): 828-47.
  • 23. Camlik G, Bilakaya B, Ozsoy Y, Degim IT. A new approach for the treatment of Alzheimer's disease: insulin-quantum dots. J Microencapsul 2024; 41(1): 18-26.
  • 24. Architha N, Ragupathi M, Shobana C, Selvankumar T, Kumar P, Lee YS, et al. Microwave-assisted green synthesis of fluorescent carbon quantum dots from Mexican Mint extract for Fe3+ detection and bio-imaging applications. Environ Res 2021; 199: 111263.
  • 25. Soledad-Flores O, Bailón-Ruiz SJ, Román-Velázquez F. Rapid synthesis of nontoxic, water-stable carbon dots using microwave irradiation. Micro 2024; 4(4): 659-69.
  • 26. Mimona MA, Rimon MIH, Zohura FT, Sony JM, Rim SI, Arup MMR, et al. Quantum dot nanomaterials: Empowering advances in optoelectronic devices. Chem Engin J Adv 2025; 21: 100704.
  • 27. Nayak AKumar, Hasnain MSaquib, Pal Dilipkumar. Natural polymers for pharmaceutical applications. Volume 3, Animal-derived polymers. Apple Academic Press; 2020. 180 p.
  • 28. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018; 10(2): 57.
  • 29. Serrano-Lotina A, Portela R, Baeza P, Alcolea-Rodriguez V, Villarroel M, Ávila P. Zeta potential as a tool for functional materials development. Catal Today 2023; 423: 113862.
  • 30. Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems - a review (Part 2). Trop J Pharm Res 2013; 12(2): 265-73.
  • 31. Tripathi S, Siddiqui MH, Kumar A, Vimal A. Nanoparticles: a promising vehicle for the delivery of therapeutic enzymes. Int Nano Lett 2023; 13(3-4): 209-21.
  • 32. Liu Y, Su G, Zhang R, Dai R, Li Z. Nanomaterials-functionalized hydrogels for the treatment of cutaneous wounds. Int J Mol Sci 2022; 24(1): 336.
  • 33. Kambhampati P. Nanoparticles, nanocrystals, and quantum dots: what are the implications of size in colloidal nanoscale materials? J Phys Chem Lett 2021; 12(20): 4769-79.
  • 34. Ashoka AH, Aparin IO, Reisch A, Klymchenko AS. Brightness of fluorescent organic nanomaterials. Chem Soc Rev 2023; 52(14): 4525-48.
  • 35. Sadjadi S. The utility of carbon dots for photocatalysis. In: Emerging Carbon Materials for Catalysis. Elsevier; 2021. p. 123-60.
  • 36. Kriukova E, LaRochelle E, Pfefer TJ, Kanniyappan U, Gioux S, Pogue B, et al. Impact of signal-to-noise ratio and contrast definition on the sensitivity assessment and benchmarking of fluorescence molecular imaging systems. J Biomed Opt 2025; 30(Suppl 1): S13703.
  • 37. Schneider LA, Korber A, Grabbe S, Dissemond J. Influence of pH on woundhealing: a new perspective for wound-therapy? Arch Dermatol Res 2007; 298(9): 413-20.
  • 38. Dissemond J, Witthoff M, Brauns TC, Haberer D, Goos M. pH-Wert des Milieus chronischer Wunden. Der Hautarzt 2003; 54(10): 959-65.
  • 39. Rajendran NK, Kumar SSD, Houreld NN, Abrahamse H. A review on nanoparticle based treatment for wound healing. J Drug Deliv Sci Technol 2018; 44: 421-30.
  • 40. Hoare TR, Kohane DS. Hydrogels in drug delivery: Progress and challenges. Polymer (Guildf) 2008; 49(8): 1993-2007.
  • 41. Tai A, Bianchini R, Jachowicz J. Texture analysis of cosmetic/pharmaceutical raw materials and formulations. Int J Cosmet Sci 2014; 36(4): 291-304.
  • 42. Boateng JS, Matthews KH, Stevens HNE, Eccleston GM. Wound healing dressings and drug delivery systems: a review. J Pharm Sci 2008; 97(8): 2892-923.
  • 43. AL-Smadi K, Ali M, Zhu J, Abdoh A, Phan K, Mohammed Y. Advances in characterization of transdermal and topical products using texture analyzer systems. AAPS PharmSciTech 2025; 26(5): 157.
  • 44. Lim SY, Shen W, Gao Z. Carbon quantum dots and their applications. Chem Soc Rev 2015; 44(1): 362-81.
  • 45. Molaei MJ. Carbon quantum dots and their biomedical and therapeutic applications: A review. RSC Adv 2019; 9(12): 6460-81.
  • 46. Gardikiotis I, Cojocaru FD, Mihai CT, Balan V, Dodi G. Borrowing the features of biopolymers for emerging wound healing dressings: a review. Int J Mol Sci 2022; 23(15): 8778.
  • 47. Lu S, Chen Z, Tu H, Liu H, Liu Y, Chen S, et al. Multifunctional carbon quantum dots decorated self-healing hydrogel for highly effective treatment of superbug infected wounds. Chem Engin J 2024; 480: 148218.
  • 48. Kuznietsova H, Ishchuk A, Byelinska I, Lysenko T, Melnytsky V, Ogloblya O, et al. Carbon dot based dressing for therapy of chemically-induced cutaneous burns. Sci Rep 2025; 15(1): 11019.
  • 49. Bajaj S, Singla D, Sakhuja N. Stability testing of pharmaceutical products. J Appl Pharm Sci 2012; 2(3): 129-38

Bromelain-Derived Carbon Quantum Dots in Hydrogel Formulations for Enhanced Wound Healing

Year 2025, Volume: 15 Issue: 3, 276 - 286, 31.12.2025
https://doi.org/10.26650/experimed.1768549

Abstract

Objective: This study aimed to explore the wound healing potential of bromelain carbon quantum dots (BCQDs), synthesized using microwave technology, incorporated into hydrogel formulations.

Materials and Methods: BCQDs were synthesized using 0.2 g bromelain and 1 mL distilled water at 140 °C. The particle size, polydispersity index (PDI) (%), zeta potential, and quantum yield (%) were measured. Hydrogels with three different carbomer concentrations (0.75%, 1%, and 1.5%) were prepared. Their viscosity, pH, texture profile, spreadability, in vitro release, MTT cytotoxicity, and wound healing properties were evaluated in the HaCaT cell line.

Results: BCQDs showed blue fluorescence under UV light (365 nm), with a particle size of 9.47 ± 0.02 nm, a PDI of 18.14%, and a zeta potential of −10.03 mV. The quantum yield was 91.7%. The pH of the formulations ranged from 3.6 to 4.4, and the viscosity ranged from 11.7 to 20.6 P. In vitro release was less than 10% in the gels without BCQDs, while the release exceeded 95% in the F2-BCQDs formulation. The MTT assay showed over 80% cell viability at concentrations up to 20 mg/mL. The scratch assay indicated significantly enhanced cell migration in the BCQDs group after 48 h compared with the control (p<0.05).

Conclusion: BCQDs-hydrogels stand out as innovative topical delivery systems that promote rapid and effective wound healing due to their superior physicochemical properties and biocompatibility.

References

  • 1. Anderson SE, Meade BJ. Potential health effects associated with dermal exposure to occupational chemicals. Environ Health Insights 2014; 8s1: EHI.S15258.
  • 2. D?browska AK, Spano F, Derler S, Adlhart C, Spencer ND, Rossi RM. The relationship between skin function, barrier properties, and body?dependent factors. Skin Res Technol 2018; 24(2): 165-74.
  • 3. Bartold M, Ivanovski S. Biological processes and factors involved in soft and hard tissue healing. Periodontol 2000 2025; 97(1): 16-42.
  • 4. Vicente-da-Silva JV, Pereira JO da SL, do Carmo FA, Patricio BF de C. Skin and wound healing: conventional dosage versus nanobased emulsions forms. ACS Omega 2025; 10(13): 12837-55.
  • 5. Fernandez-Guarino M, Naharro-Rodriguez J, Bacci S. Aberrances of the wound healing process: a review. Cosmetics 2024; 11(6): 209.
  • 6. Saghazadeh S, Rinoldi C, Schot M, Kashaf SS, Sharifi F, Jalilian E, et al. Drug delivery systems and materials for wound healing applications. Adv Drug Deliv Rev 2018; 127: 138-66.
  • 7. Tiwari R, Pathak K. Local Drug Delivery Strategies towards wound healing. Pharmaceutics 2023; 15(2): 634.
  • 8. Liu H, Wang C, Li C, Qin Y, Wang Z, Yang F, et al. A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing. RSC Adv 2018; 8(14): 7533-49.
  • 9. Rathnavelu V, Alitheen NB, Sohila S, Kanagesan S, Ramesh R. Potential role of bromelain in clinical and therapeutic applications. Biomed Rep 2016; 5(3): 283-8.
  • 10. Fathi AN, Sakhaie MH, Babaei S, Babaei S, Slimabad F, Babaei S. Use of bromelain in cutaneous wound healing in streptozocin-induced diabetic rats: an experimental model. J Wound Care 2020; 29(9): 488-95.
  • 11. Bayat S, Rabbani Zabihi A, Amel Farzad S, Movaffagh J, Hashemi E, Arabzadeh S, et al. Evaluation of debridement effects of bromelain-loaded sodium alginate nanoparticles incorporated into chitosan hydrogel in animal models. Iran J Basic Med Sci. 2021 24(10):1404-12.
  • 12. Güven GK, Okur ME, Ayla Ş, Çalışkan G, Al MN, Gülüm L, et al. Boron-doped carbon quantum dots: A biocompatible nanoplatform for targeted cancer theranostics. Int J Pharm 2025; 679: 125745.
  • 13. Camlik G, Bilakaya B, Küpeli Akkol E, Velaro AJ, Wasnik S, Muhar AM, et al. Oral active carbon quantum dots for diabetes. Pharmaceuticals 2024; 17(10): 1395.
  • 14. Camlik G, Bilakaya B, Güven GK, Akkol EK, Degim Z, Sobarzo-Sánchez E, et al. Quantum drugs (Q-Drugs): a new discovery and taboo breaking approach; producing carbon quantum dots from drug molecules. Pharmaceuticals 2025; 18(6): 767.
  • 15. Çağlar Eş, Karaotmarlı Güven G, Üstündağ Okur N. Preparation and characterization of carbopol based hydrogels containing dexpanthenol. J Fac Pharm Ankara 2023; 47(3): 770-83.
  • 16. Nasution H, Harahap H, Dalimunthe NF, Ginting MHS, Jaafar M, Tan OOH, et al. Hydrogel and effects of crosslinking agent on cellulose-based hydrogels: a review. Gels 2022; 8(9): 568.
  • 17. Chamkouri H. A review of hydrogels, their properties and applications in medicine. Am J Biomed Sci Res 2021; 11(6): 485-93.
  • 18. Camlik G, Ozakca I, Bilakaya B, Ozcelikay AT, Velaro AJ, Wasnik S, et al. Development of composite carbon quantum dots-insulin formulation for oral administration. J Drug Deliv Sci Technol 2022; 76: 103833.
  • 19. Alkian I, Sutanto H, Hadiyanto. Quantum yield optimization of carbon dots using response surface methodology and its application as control of Fe3+ ion levels in drinking water. Mater Res Express 2022; 9(1): 015702.
  • 20. Chaudhary H, Kohli K, Amin S, Rathee P, Kumar V. Optimization and formulation design of gels of diclofenac and curcumin for transdermal drug delivery by box-behnken statistical design. J Pharm Sci 2011; 100(2): 580-93.
  • 21. Oliveira MB, Calixto G, Graminha M, Cerecetto H, González M, Chorilli M. Development, characterization, and in vitro biological performance of fluconazole-loaded microemulsions for the topical treatment of cutaneous leishmaniasis. Biomed Res Int 2015; 2015: 396894.
  • 22. Mirani A, Kundaikar H, Velhal S, Patel V, Bandivdekar A, Degani M, et al. Tetrahydrocurcumin-loaded vaginal nanomicrobicide for prophylaxis of HIV/ AIDS: in silico study, formulation development, and in vitro evaluation. Drug Deliv Transl Res 2019; 9(4): 828-47.
  • 23. Camlik G, Bilakaya B, Ozsoy Y, Degim IT. A new approach for the treatment of Alzheimer's disease: insulin-quantum dots. J Microencapsul 2024; 41(1): 18-26.
  • 24. Architha N, Ragupathi M, Shobana C, Selvankumar T, Kumar P, Lee YS, et al. Microwave-assisted green synthesis of fluorescent carbon quantum dots from Mexican Mint extract for Fe3+ detection and bio-imaging applications. Environ Res 2021; 199: 111263.
  • 25. Soledad-Flores O, Bailón-Ruiz SJ, Román-Velázquez F. Rapid synthesis of nontoxic, water-stable carbon dots using microwave irradiation. Micro 2024; 4(4): 659-69.
  • 26. Mimona MA, Rimon MIH, Zohura FT, Sony JM, Rim SI, Arup MMR, et al. Quantum dot nanomaterials: Empowering advances in optoelectronic devices. Chem Engin J Adv 2025; 21: 100704.
  • 27. Nayak AKumar, Hasnain MSaquib, Pal Dilipkumar. Natural polymers for pharmaceutical applications. Volume 3, Animal-derived polymers. Apple Academic Press; 2020. 180 p.
  • 28. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018; 10(2): 57.
  • 29. Serrano-Lotina A, Portela R, Baeza P, Alcolea-Rodriguez V, Villarroel M, Ávila P. Zeta potential as a tool for functional materials development. Catal Today 2023; 423: 113862.
  • 30. Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems - a review (Part 2). Trop J Pharm Res 2013; 12(2): 265-73.
  • 31. Tripathi S, Siddiqui MH, Kumar A, Vimal A. Nanoparticles: a promising vehicle for the delivery of therapeutic enzymes. Int Nano Lett 2023; 13(3-4): 209-21.
  • 32. Liu Y, Su G, Zhang R, Dai R, Li Z. Nanomaterials-functionalized hydrogels for the treatment of cutaneous wounds. Int J Mol Sci 2022; 24(1): 336.
  • 33. Kambhampati P. Nanoparticles, nanocrystals, and quantum dots: what are the implications of size in colloidal nanoscale materials? J Phys Chem Lett 2021; 12(20): 4769-79.
  • 34. Ashoka AH, Aparin IO, Reisch A, Klymchenko AS. Brightness of fluorescent organic nanomaterials. Chem Soc Rev 2023; 52(14): 4525-48.
  • 35. Sadjadi S. The utility of carbon dots for photocatalysis. In: Emerging Carbon Materials for Catalysis. Elsevier; 2021. p. 123-60.
  • 36. Kriukova E, LaRochelle E, Pfefer TJ, Kanniyappan U, Gioux S, Pogue B, et al. Impact of signal-to-noise ratio and contrast definition on the sensitivity assessment and benchmarking of fluorescence molecular imaging systems. J Biomed Opt 2025; 30(Suppl 1): S13703.
  • 37. Schneider LA, Korber A, Grabbe S, Dissemond J. Influence of pH on woundhealing: a new perspective for wound-therapy? Arch Dermatol Res 2007; 298(9): 413-20.
  • 38. Dissemond J, Witthoff M, Brauns TC, Haberer D, Goos M. pH-Wert des Milieus chronischer Wunden. Der Hautarzt 2003; 54(10): 959-65.
  • 39. Rajendran NK, Kumar SSD, Houreld NN, Abrahamse H. A review on nanoparticle based treatment for wound healing. J Drug Deliv Sci Technol 2018; 44: 421-30.
  • 40. Hoare TR, Kohane DS. Hydrogels in drug delivery: Progress and challenges. Polymer (Guildf) 2008; 49(8): 1993-2007.
  • 41. Tai A, Bianchini R, Jachowicz J. Texture analysis of cosmetic/pharmaceutical raw materials and formulations. Int J Cosmet Sci 2014; 36(4): 291-304.
  • 42. Boateng JS, Matthews KH, Stevens HNE, Eccleston GM. Wound healing dressings and drug delivery systems: a review. J Pharm Sci 2008; 97(8): 2892-923.
  • 43. AL-Smadi K, Ali M, Zhu J, Abdoh A, Phan K, Mohammed Y. Advances in characterization of transdermal and topical products using texture analyzer systems. AAPS PharmSciTech 2025; 26(5): 157.
  • 44. Lim SY, Shen W, Gao Z. Carbon quantum dots and their applications. Chem Soc Rev 2015; 44(1): 362-81.
  • 45. Molaei MJ. Carbon quantum dots and their biomedical and therapeutic applications: A review. RSC Adv 2019; 9(12): 6460-81.
  • 46. Gardikiotis I, Cojocaru FD, Mihai CT, Balan V, Dodi G. Borrowing the features of biopolymers for emerging wound healing dressings: a review. Int J Mol Sci 2022; 23(15): 8778.
  • 47. Lu S, Chen Z, Tu H, Liu H, Liu Y, Chen S, et al. Multifunctional carbon quantum dots decorated self-healing hydrogel for highly effective treatment of superbug infected wounds. Chem Engin J 2024; 480: 148218.
  • 48. Kuznietsova H, Ishchuk A, Byelinska I, Lysenko T, Melnytsky V, Ogloblya O, et al. Carbon dot based dressing for therapy of chemically-induced cutaneous burns. Sci Rep 2025; 15(1): 11019.
  • 49. Bajaj S, Singla D, Sakhuja N. Stability testing of pharmaceutical products. J Appl Pharm Sci 2012; 2(3): 129-38
There are 49 citations in total.

Details

Primary Language English
Subjects Analytical Biochemistry
Journal Section Research Article
Authors

Gamze Çamlık 0000-0003-3282-8307

Gökçe Karaotmarlı Güven 0000-0001-9248-2526

Ayşe Şeyma Büyük 0000-0001-8934-0359

Tugce Boran 0000-0003-4302-1947

İsmail Tuncer Değim 0000-0002-9329-4698

Submission Date August 19, 2025
Acceptance Date November 17, 2025
Publication Date December 31, 2025
Published in Issue Year 2025 Volume: 15 Issue: 3

Cite

Vancouver Çamlık G, Karaotmarlı Güven G, Büyük AŞ, Boran T, Değim İT. Bromelain-Derived Carbon Quantum Dots in Hydrogel Formulations for Enhanced Wound Healing. Experimed. 2025;15(3):276-8.