Development of a Sprayable Thermosensitive Hydrogel Containing Rambutan (Nephelium Lappaceum L) Leaf Extract for Diabetic Wound Therapy

  • Khairun Nisa’ eng
  • Tarisha Elmaningtyas Zahro eng
  • Ayu Dini Nurrohmah eng
  • Dini Hanifah Faculty of Pharmacy, Universitas Ahmad Dahlan, Jl. Prof. Dr Soepomo Sh, Yogyakarta, Indonesia
  • Muhammad Farid Universitas Ahmad Dahlan
  • Deasy Vanda Pertiwi eng
DOI: https://doi.org/10.5937/scriptamed57-61263

Sažetak


Background/Aim: Diabetic wounds are challenging to treat due to impaired healing processes. This study aimed to develop a sprayable thermosensitive hydrogel incorporating rambutan (Nephelium lappaceum L) leaf extract, known for its phytochemical wound healing potential.

Methods: Rambutan leaves were extracted via 70 % ethanol maceration. Qualitative and quantitative analyses confirmed the presence of tannins and flavonoids. The extract was formulated into thermosensitive hydrogels (F1–F3) using sodium alginate, Poloxamer 407 and Poloxamer 188. Physical properties were evaluated and wound healing efficacy was tested on diabetic rats over 21 days using a full-thickness wound model.

Results: The extract yielded 25.44 % with tannin and flavonoid contents of 2.94 % and 5.73 %, respectively. All formulations were homogeneous, pH-balanced (4.52–5.03) and met ideal criteria for spreadability, gelation, swelling and viscosity. In vivo tests showed F3 had the highest wound healing rate (81.25 %), approaching the normal control (84.00 %) and outperforming the reference drug (61.67 %). Statistical analysis indicated significant differences (p < 0.05).

Conclusion: The thermosensitive hydrogel with rambutan leaf extract effectively accelerates diabetic wound healing and shows potential as a topical therapy.

Reference

Banday MZ, Sameer AS, Nissar S. Pathophysiology of diabetes: an overview. Avicenna J Med. 2020;10:174-88. doi: 10.4103/ajm.ajm_53_20.

Galindo RJ, Trujillo JM, Low Wang CC, McCoy RG. Advances in the management of type 2 diabetes in adults. BMJ Med. 2023;2:e000372. doi: 10.1136/bmjmed-2022-000372.

Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of type 2 diabetes—global burden of disease and forecasted trends. J Epidemiol Glob Health. 2020;10:107-11. doi: 10.2991/jegh.k.191028.001.

Sridharan K, Sivaramakrishnan G. Growth factors for diabetic foot ulcers: mixed treatment comparison analysis of randomized clinical trials. Br J Clin Pharmacol. 2018;84:434-44. doi: 10.1111/bcp.13470.

Vikram M, Iskandar D, Ardiyanto A, Hasan H, Nur MJ. Prevalence of diabetic foot ulcers in patients with type 2 diabetes mellitus. J La Medihealtico. 2024;5:1215-23. doi: 10.37899/journallamedihealtico.v5i6.1769.

Raja JM, Maturana MA, Kayali S, Khouzam A, Efeovbokhan N. Diabetic foot ulcer: a comprehensive review of pathophysiology and management modalities. World J Clin Cases. 2023;11:1684-93. doi: 10.12998/wjcc.v11.i8.1684.

Wang X, Yuan CX, Xu B, Yu Z. Diabetic foot ulcers: classification, risk factors and management. World J Diabetes. 2022;13:1049-65. doi: 10.4239/wjd.v13.i12.1049.

Fuente Núñez C de la, Cesaro A, Hancock REW. Antibiotic failure: beyond antimicrobial resistance. Drug Resist Updat. 2023;71:101012. doi: 10.1016/j.drup.2023.101012.

Lim JZM, Ng NSL, Thomas C. Prevention and treatment of diabetic foot ulcers. J R Soc Med. 2017;110:104-9. doi: 10.1177/0141076816688346.

Tsong JL, Goh LPW, Gansau JA, How SE. Review of Nephelium lappaceum and Nephelium ramboutan ake: a high potential supplement. Molecules. 2021;26. doi: 10.3390/molecules26227005.

Afzaal M, Saeed F, Bibi M, Ejaz A, Shah YA, Faisal Z, et al. Nutritional, pharmaceutical, and functional aspects of rambutan in industrial perspective: an updated review. Food Sci Nutr. 2023;11:3675-85. doi: 10.1002/fsn3.3379.

Hernández Hernández C, Aguilar CN, Rodríguez Herrera R, Flores Gallegos AC, Morlett Chávez J, Govea Salas M, et al. Rambutan (Nephelium lappaceum L.): nutritional and functional properties. Trends Food Sci Technol. 2019;85:201-10. doi: 10.1016/j.tifs.2019.01.018.

Lee YR, Cho HM, Park EJ, Zhang M, Doan TP, Lee BW, et al. Metabolite profiling of rambutan (Nephelium lappaceum L.) seeds using UPLC QTOF MS/MS and senomorphic effects in aged human dermal fibroblasts. Nutrients. 2020;12. doi: 10.3390/nu12051430.

Florenly F, Wijaya CD, Kelvin K, Bao NPG, Dung PCT. Antibacterial efficacy of nanoparticles of rambutan peel extracts (Nephelium lappaceum L.) compared to microparticles against oral bacteria. e GiGi. 2022;10:95. doi: 10.35790/eg.v10i1.39001.

Rizkita LD, Ariani R, Farid M, Rastrani A, Ramadhania WA, Putri RAE. Inhibitory effects of rambutan (Nephelium lappaceum L.) leaves ethanolic extract on methicillin resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes. Sains Medika J Kedokteran Kesehatan. 2024;15:68. doi: 10.30659/sainsmed.v15i2.40155.

Liu Z, Tang W, Liu J, Han Y, Yan Q, Dong Y, et al. A novel sprayable thermosensitive hydrogel coupled with zinc modified metformin promotes the healing of skin wound. Bioact Mater. 2023;20:610-26. doi: 10.1016/j.bioactmat.2022.06.008.

Fan R, Cheng Y, Wang R, Zhang T, Zhang H, Li J, et al. Thermosensitive hydrogels and advances in their application in disease therapy. Polymers (Basel). 2022;14. doi: 10.3390/polym14122379.

Abbasi AR, Sohail M, Minhas MU, Khaliq T, Kousar M, Khan S, et al. Bioinspired sodium alginate based thermosensitive hydrogel membranes for accelerated wound healing. Int J Biol Macromol. 2020;155:751-65. doi: 10.1016/j.ijbiomac.2020.03.248.

Ruan P, Liang S, Lu B, Fan HJ, Zhou J. Design strategies for high energy density aqueous zinc batteries. Angew Chem Int Ed. 2022;61. doi: 10.1002/anie.202200598.

Wang Q, Zuo Z, Cheung CKC, Leung SSY. Updates on thermosensitive hydrogel for nasal, ocular and cutaneous delivery. Int J Pharm. 2019;559:86-101. doi: 10.1016/j.ijpharm.2019.01.030.

Tingting Z, Xiuli Z, Kun W, Liping S, Yongliang Z. A review: extraction, phytochemicals, and biological activities of rambutan (Nephelium lappaceum L.) peel extract. Heliyon. 2022;8:e11314. doi: 10.1016/j.heliyon.2022.e11314.

Ramos R, Bezerra I, Ferreira M, Soares L. Spectrophotometric quantification of flavonoids in herbal material, crude extract, and fractions from leaves of Eugenia uniflora Linn. Pharmacogn Res. 2017;9:253-60. doi: 10.4103/pr.pr_143_16.

Ghasemi A, Jeddi S. Streptozotocin as a tool for induction of rat models of diabetes: a practical guide. EXCLI J. 2023;22:274-94. doi: 10.17179/excli2022-5720.

Ahmadi Noorbakhsh S, Farajli Abbasi M, Ghasemi M, Bayat G, Davoodian N, Sharif Paghaleh E, et al. Anesthesia and analgesia for common research models of adult mice. Lab Anim Res. 2022;38. doi: 10.1186/s42826-022-00150-3.

Chigurupati S, Krishnan Selvarajan K, Mani V. Identification of Nephelium lappaceum leaves phenolic and flavonoid component with radical scavenging, antidiabetic and antibacterial potential. Indian J Tradit Knowl. 2019;18:360-65.

Dąbrowska A, Mielańczuk M, Syczewski M. Raman spectroscopy and SEM/EDS investigation of the primary sources of microplastics from cosmetics available in Poland. Chemosphere. 2022;308:136407. doi: 10.1016/j.chemosphere.2022.136407.

Chen Z, Lang G, Xu X, Liang X, Han Y, Han Y. The role of NF kappaB in the inflammatory processes related to dental caries, pulpitis, apical periodontitis, and periodontitis—a narrative review. PeerJ. 2024;12:e17953. doi: 10.7717/peerj.17953.

Hisam EEA, Rofiee MS, Khalid AM, Jalaluddin AF, Mohamad Yusof MI, Idris MH, et al. Combined extract of Moringa oleifera and Centella asiatica modulates oxidative stress and senescence in hydrogen peroxide induced human dermal fibroblasts. Turk J Biol. 2018;42:33-44. doi: 10.3906/biy-1708-23.

Asad MI, Khan D, Rehman AU, Elaissari A, Ahmed N. Development and in vitro/in vivo evaluation of pH sensitive polymeric nanoparticles loaded hydrogel for the management of psoriasis. Nanomaterials. 2021;11. doi: 10.3390/nano11123433.

Soundaranathan M, Vivattanaseth P, Walsh E, Pitt K, Johnston B, Markl D. Quantification of swelling characteristics of pharmaceutical particles. Int J Pharm. 2020;590:119903. doi: 10.1016/j.ijpharm.2020.119903.

Yang Y, Ma Y, Wang J, Zhang R, Wu M, Zhong S, et al. An injectable thermosensitive hydrogel with antibacterial and antioxidation properties for accelerating wound healing. ACS Appl Mater Interfaces. 2024;16:46053-65. doi: 10.1021/acsami.4c09465.

Gu R, Zhou H, Zhang Z, Lv Y, Pan Y, Li Q, et al. Research progress related to thermosensitive hydrogel dressings in wound healing: a review. Nanoscale Adv. 2023;5:6017-37. doi: 10.1039/d3na00407d.

Objavljeno
2026/06/29
Broj časopisa
Vol. 57 Br. 3 (2026): May-Jun
Rubrika
Originalni naučni članak
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