ABSTRACT:
Chronic diabetic wounds, particularly diabetic foot ulcers (DFUs), present significant challenges in clinical management due to impaired healing processes and limitations of conventional treatments. This study explores an innovative approach to diabetic wound care through the development and evaluation of Rutin-loaded Solid Lipid Nanoparticles (RN-SLNs). Rutin, a bioflavonoid with potent anti-inflammatory, antioxidant, and pro-angiogenic properties, was encapsulated within biocompatible lipid nanocarriers to enhance its therapeutic efficacy in wound healing. The RN-SLNs were synthesized using an optimized hot homogenization technique followed by ultrasonication, resulting in a stable nanoformulation. The study aimed to assess the in vivo efficacy of RN-SLNs in managing diabetic wounds, focusing on key healing parameters. This novel drug delivery system addresses the challenges of topical drug administration in chronic wounds, including drug degradation and uncontrolled release. Results demonstrate the potential of RN-SLNs to modulate the wound healing environment, promoting tissue regeneration and mitigating the chronic inflammation characteristic of diabetic wounds. The successful development and evaluation of RN-SLNs represent a significant step towards translating nanotechnology-based approaches into clinical wound care. This research opens avenues for personalized nanomedicine strategies in diabetic wound management, potentially improving patient outcomes and quality of life.
Cite this article:
Rahul Yadav, Anand Mahalvar. In vivo Efficacy of Rutin-loaded Nanolipid Carrier for the Healing and Management of Diabetic Wound. Research Journal of Pharmacy and Technology. 2025;18(6):2826-3. doi: 10.52711/0974-360X.2025.00405
Cite(Electronic):
Rahul Yadav, Anand Mahalvar. In vivo Efficacy of Rutin-loaded Nanolipid Carrier for the Healing and Management of Diabetic Wound. Research Journal of Pharmacy and Technology. 2025;18(6):2826-3. doi: 10.52711/0974-360X.2025.00405 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-6-58
7. REFERENCES:
1. C.H. Lee, S.H. Chang, W.J. Chen, K.C. Hung, Y.H. Lin, S.J. Liu, M.J. Hsieh, J.H.S. Pang, J.H. Juang. Augmentation of diabetic wound healing and enhancement of collagen content using nanofibrous glucophage-loaded collagen/PLGA scaffold membranes., J. Colloid Interface Sci. 2015; 439: 88–97. https://doi.org/10.1016/j.jcis.2014.10.028.
2. K. Yadav. Nanotechnology in diabetes Management: Revolutionizing treatment and diagnostics. J. Mol. Liq. 2024; 414: 126117. https://doi.org/https://doi.org/10.1016/j.molliq.2024.126117.
3. R.G. Frykberg, J. Banks, Challenges in the Treatment of Chronic Wounds., Adv. Wound Care. 2015; 4: 560–582. https://doi.org/10.1089/wound.2015.0635.
4. S.K. Singh, S.D. Dwivedi, K. Yadav, K. Shah, N.S. Chauhan, M. Pradhan, M.R. Singh, D. Singh, Novel Biotherapeutics Targeting Biomolecular and Cellular Approaches in Diabetic Wound Healing, Biomedicines. 2023; 11. https://doi.org/10.3390/biomedicines11020613.
5. H. Yadav, A. Mahalvar, M. Pradhan, K. Yadav, K. Kumar Sahu, R. Yadav, Exploring the potential of phytochemicals and nanomaterial: a boon to antimicrobial treatment, Med. Drug Discov. 2023; 17: 100151. https://doi.org/https://doi.org/10.1016/j.medidd.2023.100151.
6. K. Yadav, K. Kumar Sahu, Sucheta, R. Yadav, W. Raza, S. Minz, M. Rawat Singh, D. Singh, M. Pradhan, A complex molecular landscape to drug delivery concept for achieving precise therapy in psoriasis, Med. Drug Discov. 2024; 22: 100183. https://doi.org/https://doi.org/10.1016/j.medidd.2024.100183.
7. S. Patel, S.D. Dwivedi, K. Yadav, J.R. Kanwar, M.R. Singh, D. Singh, Pathogenesis and Molecular Targets in Treatment of Diabetic Wounds, in: Obes. Diabetes, J. Faintuc, Springer Nature Switzerland AG 2020, 2020: pp. 747–758. https://doi.org/10.1007/978-3-030-53370-0_55.
8. K. Yadav, M. Pradhan, D. Singh, M.R. Singh, Targeting autoimmune disorders through metal nanoformulation in overcoming the fences of conventional treatment approaches, in: N. Rezaei (Ed.), Transl. Autoimmun., Academic Press. 2022: 361–393. https://doi.org/10.1016/b978-0-12-824390-9.00017-7.
9. K. Yadav, D. Singh, M.R. Singh, Novel archetype in psoriasis management bridging molecular dynamics in exploring novel therapies, Eur. J. Pharmacol. 2021; 907: 174254. https://doi.org/https://doi.org/10.1016/j.ejphar.2021.174254.
10. M.R. Singh, K. Yadav, N.D. Chaurasiya, D. Singh, Immune System and Mechanism of Immunomodulation, in: N.S. Sangwan, M.A. Farag, L.V. Modolo (Eds.), Plants Phytomolecules Immunomodulation Recent Trends Adv., Springer Nature Singapore, Singapore. 2022: 1–31. https://doi.org/10.1007/978-981-16-8117-2_1.
11. S.F. Spampinato, G.I. Caruso, R. De Pasquale, M.A. Sortino, S. Merlo, The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs., Pharmaceuticals (Basel). 2020; 13. https://doi.org/10.3390/ph13040060.
12. R. Yadav, M. Pradhan, K. Yadav, A. Mahalvar, H. Yadav, Present scenarios and future prospects of herbal nanomedicine for antifungal therapy, J. Drug Deliv. Sci. Technol. 2022; 74: 103430. https://doi.org/https://doi.org/10.1016/j.jddst.2022.103430.
13. K. Yadav, M. Pradhan, D. Singh, M.R. Singh, Macrophage-Associated Disorders: Pathophysiology, Treatment Challenges, and Possible Solutions, in: Macrophage Target. Deliv. Syst., Springer, 2022.
14. S. Saghazadeh, C. Rinoldi, M. Schot, S.S. Kashaf, F. Sharifi, E. Jalilian, K. Nuutila, G. Giatsidis, P. Mostafalu, H. Derakhshandeh, K. Yue, W. Swieszkowski, A. Memic, A. Tamayol, A. Khademhosseini, Drug delivery systems and materials for wound healing applications., Adv. Drug Deliv. Rev. 2018; 127: 138–166. https://doi.org/10.1016/j.addr.2018.04.008.
15. K. Yadav, D. Singh, M.R. Singh, M. Pradhan, Nano-constructs targeting the primary cellular energy source of cancer cells for modulating tumor progression, OpenNano. 2022; 8: 100107. https://doi.org/https://doi.org/10.1016/j.onano.2022.100107.
16. K. Yadav, K.K. Sahu, Sucheta, S.P.E. Gnanakani, P. Sure, R. Vijayalakshmi, V.D. Sundar, V. Sharma, R. Antil, M. Jha, S. Minz, A. Bagchi, M. Pradhan, Biomedical applications of nanomaterials in the advancement of nucleic acid therapy: Mechanistic challenges, delivery strategies, and therapeutic applications, Int. J. Biol. Macromol. 2023; 241: 124582. https://doi.org/https://doi.org/10.1016/j.ijbiomac.2023.124582.
17. D.S. K Yadav MR Singh, Nanovesicles delivery approach for targeting steroid mediated mechanism of antipsoriatic therapeutics, J. Drug Deliv. Sci. Technol. 2021: 102688.
18. A. Kushwaha, L. Goswami, B.S. Kim, Nanomaterial-Based Therapy for Wound Healing., Nanomater. (Basel, Switzerland). 2022; 12: https://doi.org/10.3390/nano12040618.
19. A. Ismail, E. El-Biyally, W. Sakran, An Innovative Approach for Formulation of Rutin Tablets Targeted for Colon Cancer Treatment, AAPS PharmSciTech. 2023; 24: 68. https://doi.org/10.1208/s12249-023-02518-7.
20. S.C. Sundararaj, M. Al-Sabbagh, C.L. Rabek, T.D. Dziubla, M. V Thomas, D.A. Puleo, Comparison of sequential drug release in vitro and in vivo., J. Biomed. Mater. Res. B. Appl. Biomater. 2016; 104: 1302–1310. https://doi.org/10.1002/jbm.b.33472.
21. R. Sheoran, S.L. Khokra, V. Chawla, H. Dureja, Recent Patents, Formulation Techniques, Classification and Characterization of Liposomes., Recent Pat. Nanotechnol. 2019; 13: 17–27. https://doi.org/10.2174/1872210513666181127110413.
22. O. Katare, K. Raza, B. Singh, S. Dogra, Novel drug delivery systems in topical treatment of psoriasis: Rigors and vigors, in: Indian J. Dermatol. Venereol. Leprol. 2010: 612–621. https://doi.org/10.4103/0378-6323.72451.
23. M. Pradhan, K. Yadav, D. Singh, M.R. Singh, Topical delivery of fluocinolone acetonide integrated NLCs and salicylic acid enriched gel: A potential and synergistic approach in the management of psoriasis, J. Drug Deliv. Sci. Technol. 2021; 61: 102282. https://doi.org/10.1016/j.jddst.2020.102282.
24. M. Pradhan, A. Alexander, M.R. Singh, D. Singh, S. Saraf, S. Saraf, K. Yadav, Ajazuddin, Statistically optimized calcipotriol fused nanostructured lipid carriers for effectual topical treatment of psoriasis, J. Drug Deliv. Sci. Technol. 2020: 102168. https://doi.org/https://doi.org/10.1016/j.jddst.2020.102168.
25. K.K. Sahu, M. Pradhan, D. Singh, M.R. Singh, K. Yadav, Non-viral nucleic acid delivery approach: A boon for state-of-the-art gene delivery, J. Drug Deliv. Sci. Technol. 2023; 80: 104152. https://doi.org/https://doi.org/10.1016/j.jddst.2023.104152.
26. V.T. Arantes, A.A.G. Faraco, F.B. Ferreira, C.A. Oliveira, E. Martins-Santos, P. Cassini-Vieira, L.S. Barcelos, L.A.M. Ferreira, G.A.C. Goulart, Retinoic acid-loaded solid lipid nanoparticles surrounded by chitosan film support diabetic wound healing in in vivo study., Colloids Surf. B. Biointerfaces. 2020; 188: 110749. https://doi.org/10.1016/j.colsurfb.2019.110749.
27. K. Yadav, D. Singh, M.R. Singh, Development and characterization of corticosteroid loaded lipid carrier system for psoriasis, Res. J. Pharm. Technol. 14 (2021) 966–970. https://doi.org/10.5958/0974-360x.2021.00172.4.
28. R. Chadha, S. Gupta, N. Pathak, Artesunate-loaded chitosan/lecithin nanoparticles: preparation, characterization, and in vivo studies., Drug Dev. Ind. Pharm. 2012; 38: 1538–1546. https://doi.org/10.3109/03639045.2012.658812.
29. N.V.S. Priyanka, P. Neeraja, T. Mangilal, M.R. Kumar, Formulation and evaluation of gel loaded with microspheres of apremilast for transdermal delivery system, Asian J. Pharm. Clin. Res. 2019: 411–417. https://doi.org/10.22159/ajpcr.2019.v12i2.29374.
30. J.Y. Fang, C.L. Fang, C.H. Liu, Y.H. Su, Lipid nanoparticles as vehicles for topical psoralen delivery: Solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC), Eur. J. Pharm. Biopharm. 2008; 70: 633–640. https://doi.org/10.1016/j.ejpb.2008.05.008.
31. M. Walunj, S. Doppalapudi, U. Bulbake, W. Khan, Preparation, characterization, and in vivo evaluation of cyclosporine cationic liposomes for the treatment of psoriasis., J. Liposome Res. 2020; 30: 68–79. https://doi.org/10.1080/08982104.2019.1593449.
32. J.R. Madan, P.A. Khude, K. Dua, Development and evaluation of solid lipid nanoparticles of mometasone furoate for topical delivery., Int. J. Pharm. Investig. 2014; 4: 60–64. https://doi.org/10.4103/2230-973X.133047.
33. S.D. Mandawgade, V.B. Patravale, Development of SLNs from natural lipids: Application to topical delivery of tretinoin, Int. J. Pharm. 363 (2008) 132–138. https://doi.org/10.1016/j.ijpharm.2008.06.028.
34. W.M. Obeidat, K. Schwabe, R.H. Müller, C.M. Keck, Preservation of nanostructured lipid carriers (NLC), Eur. J. Pharm. Biopharm. 2010; 76:56–67. https://doi.org/10.1016/j.ejpb.2010.05.001.
35. F. Müller, S. Hönzke, W.O. Luthardt, E.L. Wong, M. Unbehauen, J. Bauer, R. Haag, S. Hedtrich, E. Rühl, J. Rademann, Rhamnolipids form drug-loaded nanoparticles for dermal drug delivery, Eur. J. Pharm. Biopharm. 2017; 116: 31–37. https://doi.org/10.1016/j.ejpb.2016.12.013.
36. C. Sinico, M. Manconi, M. Peppi, F. Lai, D. Valenti, A.M. Fadda, Liposomes as carriers for dermal delivery of tretinoin: In vitro evaluation of drug permeation and vesicle-skin interaction, J. Control. Release. 2005; 103: 123–136.
37. Y. Gu, X. Tang, M. Yang, D. Yang, J. Liu, Transdermal drug delivery of triptolide-loaded nanostructured lipid carriers: Preparation, pharmacokinetic, and evaluation for rheumatoid arthritis. Int. J. Pharm. 2019; 554: 235–244. https://doi.org/10.1016/j.ijpharm.2018.11.024.
38. A.L. Laiva, F.J. O’Brien, M.B. Keogh, Innovations in gene and growth factor delivery systems for diabetic wound healing., J. Tissue Eng. Regen. Med. 12 (2018) e296–e312. https://doi.org/10.1002/term.2443.
39. T.A. Wynn, K.M. Vannella, Macrophages in Tissue Repair, Regeneration, and Fibrosis, Immunity. 2016; 44: 450–462. https://doi.org/10.1016/j.immuni.2016.02.015.
40. R. Nunan, K.G. Harding, P. Martin, Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity., Dis. Model. Mech. 2014; 7; 1205–1213. https://doi.org/10.1242/dmm.016782.
41. H. Li, X. Fu, L. Zhang, Q. Huang, Z. Wu, T. Sun, Research of PDGF-BB gel on the wound healing of diabetic rats and its pharmacodynamics., J. Surg. Res. 2008; 145: 41–48. https://doi.org/10.1016/j.jss.2007.02.044.
42. G. Crovetti, G. Martinelli, M. Issi, M. Barone, M. Guizzardi, B. Campanati, M. Moroni, A. Carabelli, Platelet gel for healing cutaneous chronic wounds., Transfus. Apher. Sci. Off. J. World Apher. Assoc. Off. J. Eur. Soc. Haemapheresis. 2004; 30: 145–151. https://doi.org/10.1016/j.transci.2004.01.004.
43. K. Yadav, D. Singh, M.R. Singh, Nanovesicles delivery approach for targeting steroid mediated mechanism of antipsoriatic therapeutics, J. Drug Deliv. Sci. Technol. 65 (2021) 102688. https://doi.org/10.1016/j.jddst.2021.102688.
44. H. Vaghasiya, A. Kumar, K. Sawant, Development of solid lipid nanoparticles based controlled release system for topical delivery of terbinafine hydrochloride, Eur. J. Pharm. Sci. 2013; 49: 311–322. https://doi.org/10.1016/j.ejps.2013.03.013.
45. R. Shukla, J. Dewangan, S. Urandur, V. Teja, M. Sharma, S. Sharma, S. Agrawal, S. Rath, R. Trivedi, P. Mishra, Multifunctional hybrid nanoconstructs facilitates intracellular localization of Doxorubicin and Genistein to enhance apoptotic and anti-angiogenic efficacy in breast adenocarcinoma, Biomater. Sci. 2019; 8. https://doi.org/10.1039/C9BM01246J.
46. N.K. Garg, G. Sharma, B. Singh, P. Nirbhavane, R.K. Tyagi, R. Shukla, O.P. Katare, Quality by Design (QbD)-enabled development of aceclofenac loaded-nano structured lipid carriers (NLCs): An improved dermatokinetic profile for inflammatory disorder(s), Int. J. Pharm. 2017; 517; 413–431. https://doi.org/10.1016/j.ijpharm.2016.12.010.
47. A. Qadir, M. Aqil, A. Ali, M.H. Warsi, M. Mujeeb, F.J. Ahmad, S. Ahmad, S. Beg, Nanostructured lipidic carriers for dual drug delivery in the management of psoriasis: Systematic optimization, dermatokinetic and preclinical evaluation, J. Drug Deliv. Sci. Technol. 2020; 57; 101775. https://doi.org/10.1016/j.jddst.2020.101775.
48. P.P. Shah, P.R. Desai, M. Singh, Effect of oleic acid modified polymeric bilayered nanoparticles on percutaneous delivery of spantide II and ketoprofen, J. Control. Release. 2012; 158: 336–345. https://doi.org/10.1016/j.jconrel.2011.11.016.
49. H. Gollavilli, A.R. Hegde, R.S. Managuli, K.V. Bhaskar, S.J. Dengale, M.S. Reddy, G. Kalthur, S. Mutalik, Naringin nano-ethosomal novel sunscreen creams: Development and performance evaluation, Colloids Surfaces B Biointerfaces. 2020; 193: 111122. https://doi.org/10.1016/j.colsurfb.2020.111122.
50. P. Patel, A.K. Parashar, M. Kaurav, K. Yadav, D. Singh, G.D. Gupta, B. Das Kurmi, A.K. Jain, K. Mishra, Nanoparticles and Nanocarriers-based Pharmaceutical Formulations, 2022.
51. P. Batheja, L. Sheihet, J. Kohn, A.J. Singer, B. Michniak-Kohn, Topical drug delivery by a polymeric nanosphere gel: Formulation optimization and in vitro and in vivo skin distribution studies, J. Control. Release. 2011; 149: 159–167. https://doi.org/10.1016/j.jconrel. 2010.10.005.
52. Y. Chu, D. Yu, P. Wang, J. Xu, D. Li, M. Ding, Nanotechnology promotes the full-thickness diabetic wound healing effect of recombinant human epidermal growth factor in diabetic rats., Wound Repair Regen. Off. Publ. Wound Heal. Soc. [and] Eur. Tissue Repair Soc. 2010; 18; 499–505.
53. K. Thakur, A. Mahajan, G. Sharma, B. Singh, K. Raza, S. Chhibber, O.P. Katare, Implementation of Quality by Design (QbD) approach in development of silver sulphadiazine loaded egg oil organogel: An improved dermatokinetic profile and therapeutic efficacy in burn wounds, Int. J. Pharm. 2020; 576: 118977.
54. M. Rahman, S. Akhter, J. Ahmad, M.Z. Ahmad, S. Beg, F.J. Ahmad, Nanomedicine-based drug targeting for psoriasis: Potentials and emerging trends in nanoscale pharmacotherapy, Expert Opin. Drug Deliv. 2015; 12: 635–652.