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Carvedilol-Loaded Cubosome Gel to Accelerate Wound Healing

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Abstract

Purpose

An attempt was made to formulate carvedilol-loaded cubosome (cubogel) to accelerate the wound healing activity. The combined effect of a natural healing agent, Moringa oleifera Lam. leaf extract and cubosomes was also studied.

Methods

Cubosomes were prepared by emulsification method. A 32 factorial design was applied to optimize independent variables: glycerol monooleate and Lutrol F127 and response variables mainly, particle size, entrapment efficiency, and drug release. Optimized formulation was incorporated in the gel base to get cubogel and was characterized for pH, drug content, and viscosity.

Results

Cubosomal formulations were of small particle size (249.2 ± 2.2 nm), exhibited high entrapment efficiency (37.1 ± 1.01%) and effectively delayed drug release (85.02 ± 0.91% within 24 h), hence was selected as optimized formulation. Cubic-shaped cubosomes were confirmed by transmission electron microcopy, having zeta potential − 29.05 mV. Cubosomes were incorporated into Carbopol 934 base (1%) to get cubogel. Texture analyzer demonstrated less spreadability due to viscous nature of cubogel. Diffusion study revealed slow diffusion of drug through the cubosomes. In vivo study was performed in rats using excision wound model; it showed rapid initiation of wound healing on day 3, closing above 94% on day 7 and scar formation on day 10, for both cubogel and cubogel with Moringa oleifera leaf extract.

Conclusion

Carvedilol-loaded cubogel in combination with Moringa oleifera leaf extract can be considered as an excellent formulation to accelerate the wound healing potential.

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Data Availability

Materials described in the manuscript, including all relevant raw data, will be freely available to any researcher wishing to use them for non-commercial purposes, without breaching participant confidentiality.

References

  1. Abazari M, Ghaffari A, Rashidzadeh H, Badeleh SM, Maleki Y. A systematic review on classification, identification, and healing process of burn wound healing. Int J Low Extrem Wounds. 2022;21(1):18–30.

    Article  PubMed  Google Scholar 

  2. Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219–29.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Salazar-Gómez A, Alonso-Castro AJ. Medicinal plants from Latin America with wound healing activity: ethnomedicine, phytochemistry, preclinical and clinical studies-a review. Pharmaceuticals. 2022;15(9):1095.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mirhaj M, Labbaf S, Tavakoli M, Seifalian AM. Emerging treatment strategies in wound care. Int Wound J. 2022;19(7):1934–54.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Almoshari Y. Development, therapeutic evaluation and theranostic applications of cubosomes on cancers: an updated review. Pharmaceutics. 2022;14(3):600.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Lim DG, Jeong W-W, Kim NA, Lim JY, Lee S-H, Shim WS, et al. Effect of the glyceryl monooleate-based lyotropic phases on skin permeation using in vitro diffusion and skin imaging. Asian J Pharm Sci. 2014;9(6):324–9.

    Article  Google Scholar 

  7. Arafa WM, Elkomy MH, Aboud HM, Ali MI, Abdel Gawad SS, Aboelhadid SM, et al. Tunable polymeric mixed micellar nanoassemblies of Lutrol F127/Gelucire 44/14 for oral delivery of praziquantel: a promising nanovector against hymenolepis nana in experimentally-infected rats. Pharmaceutics. 2022;14(10):2023.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Morsi NM, Abdelbary GA, Ahmed MA. Silver sulfadiazine based cubosome hydrogels for topical treatment of burns: development and in vitro/in vivo characterization. Eur J Pharm Biopharm. 2014;86(2):178–89.

  9. Kwon TK, Hong SK, Kim J-C. In vitro skin permeation of cubosomes containing triclosan. J Ind Eng Chem. 2012;18(1):563–7.

    Article  CAS  Google Scholar 

  10. Zakaria F, Ashari SE, Mat Azmi ID, Abdul Rahman MB. Recent advances in encapsulation of drug delivery (active substance) in cubosomes for skin diseases. J Drug Deliv Sci Technol. 2022;68: 103097.

    Article  CAS  Google Scholar 

  11. Benkel T, Zimmermann M, Zeiner J, Bravo S, Merten N, Lim VJY, et al. How carvedilol activates β2-adrenoceptors. Nat Commun. 2022;13(1):7109.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Nayak V, Chogtu B, Parimi MRA, Mahapatra AK, Vaishnav RL. Comparison of different adrenergic blockers on cutaneous wound healing in Wistar rats. Br Med Bull. 2014;2(2):371–5.

    Google Scholar 

  13. Al-Ghanayem AA, Alhussaini MS, Asad M, Joseph B. Moringa oleifera leaf extract promotes healing of infected wounds in diabetic rats: evidence of antimicrobial, antioxidant and proliferative properties. Pharmaceuticals. 2022;15(5):528.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Ali A, Garg P, Goyal R, Khan A, Negi P, Li X, et al. An efficient wound healing hydrogel based on a hydroalcoholic extract of Moringa oleifera seeds. S Afr J Bot. 2022;145:192–8.

    Article  CAS  Google Scholar 

  15. Lambole V, Kumar U. Effect of Moringa oleifera Lam. on normal and dexamethasone suppressed wound healing. Asian Pac J Trop Biomed. 2012;2(1):S219-S23.

  16. Vongsak B, Sithisarn P, Gritsanapan W. Simultaneous HPLC quantitative analysis of active compounds in leaves of Moringa oleifera Lam. J Chromatogr Sci. 2013;52(7):641–5.

    Article  PubMed  Google Scholar 

  17. Pandit A, Khandagale K, Nakhate V, Dharmadhikari N. Antifungal topical gel of leaf extract of Amaranthus viridis l. for treatment of cutaneous candidiasis. Indian Drugs. 2019;56(12):39–44.

  18. Gustafsson J, Ljusberg-Wahren H, Almgren M, Larsson K. Submicron particles of reversed lipid phases in water stabilized by a nonionic amphiphilic polymer. Langmuir. 1997;13(26):6964–71.

    Article  CAS  Google Scholar 

  19. Hamed R, Seder BY, Bardaweel SK, Qawass H. Lipid-based formulations of microemulsion-loaded oleogels for the oral delivery of carvedilol. J Dispers Sci Technol. 2021:1–11.

  20. Zhang L, Li J, Tian D, Sun L, Wang X, Tian M. Theranostic combinatorial drug-loaded coated cubosomes for enhanced targeting and efficacy against cancer cells. Cell Death Dis. 2020;11(1):1.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zewail M, PM EG, Ali MM, Abbas H. Lipidic cubic-phase leflunomide nanoparticles (cubosomes) as a potential tool for breast cancer management. Drug Deliv. 2022;29(1):1663–74.

  22. Tang X, Nail SL, Pikal MJ. Evaluation of manometric temperature measurement, a process analytical technology tool for freeze-drying: part I, product temperature measurement. AAPS PharmSciTech. 2006;7:E95–103.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sanjana A, Ahmed MG, BH JG. Development and evaluation of dexamethasone loaded cubosomes for the treatment of vitiligo. Mater Today: Proc. 2022;50:197–205.

  24. Jelvehgari M, Montazam H. Evaluation of mechanical and rheological properties of metronidazole gel as local delivery system. Arch Pharm Res. 2011;34(6):931–40.

    Article  PubMed  CAS  Google Scholar 

  25. Mahmoud NN, Hikmat S, Ghith DA, Hajeer M, Hamadneh L, Qattan D, et al. Gold nanoparticles loaded into polymeric hydrogel for wound healing in rats: effect of nanoparticles’ shape and surface modification. Int J Pharm. 2019;565:174–86.

    Article  PubMed  CAS  Google Scholar 

  26. Rajoo A, Ramanathan S, Mansor SM, Sasidharan S. Formulation and evaluation of wound healing activity of Elaeis guineensis Jacq leaves in a Staphylococcus aureus infected Sprague Dawley rat model. J Ethnopharmacol. 2021;266: 113414.

    Article  PubMed  CAS  Google Scholar 

  27. Vergara-Jimenez M, Almatrafi MM, Fernandez ML. Bioactive components in Moringa oleifera leaves protect against chronic disease. Antioxidants. 2017;6(4):91.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Karami Z, Hamidi M. Cubosomes: remarkable drug delivery potential. Drug Discov Today. 2016;21(5):789–801.

    Article  PubMed  CAS  Google Scholar 

  29. Barauskas J, Johnsson M, Joabsson F, Tiberg F. Cubic phase nanoparticles (cubosome): principles for controlling size, structure, and stability. Langmuir. 2005;21(6):2569–77.

    Article  PubMed  CAS  Google Scholar 

  30. Bei D, Marszalek J, Youan B-BC. Formulation of dacarbazine-loaded cubosomes—part I: influence of formulation variables. AAPS PharmSciTech. 2009;10:1032–9.

  31. Pan X, Han K, Peng X, Yang Z, Qin L, Zhu C, et al. Nanostructed cubosomes as advanced drug delivery system. Curr Pharm Des. 2013;19(35):6290–7.

    Article  PubMed  CAS  Google Scholar 

  32. Sengottiyan S, Mikolajczyk A, Jagiełło K, Swirog M, Puzyn T. Core, coating, or corona? The importance of considering protein coronas in nano-QSPR modeling of zeta potential. ACS Nano. 2023;17(3):1989–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Bessone CDV, Akhlaghi SP, Tártara LI, Quinteros DA, Loh W, Allemandi DA. Latanoprost-loaded phytantriol cubosomes for the treatment of glaucoma. Eur J Pharm Sci. 2021;160: 105748.

    Article  PubMed  CAS  Google Scholar 

  34. Nasr M, Ghorab MK, Abdelazem A. In vitro and in vivo evaluation of cubosomes containing 5-fluorouracil for liver targeting. Acta pharmaceutica sinica B. 2015;5(1):79–88.

    Article  PubMed  Google Scholar 

  35. Flak DK, Adamski V, Nowaczyk G, Szutkowski K, Synowitz M, Jurga S, et al. AT101-loaded cubosomes as an alternative for improved glioblastoma therapy. Int J Nanomedicine. 2020:7415–31.

  36. Alharbi WS, Hosny KM. Development and optimization of ocular in situ gels loaded with ciprofloxacin cubic liquid crystalline nanoparticles. J Drug Deliv Sci Technol. 2020;57: 101710.

    Article  CAS  Google Scholar 

  37. Tarsitano M, Mancuso A, Cristiano MC, Paolino D, Fresta M. In situ swelling formulation of glycerol-monooleate-derived lyotropic liquid crystals proposed for local vaginal application. Molecules. 2022;27(19):6295.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Lai J, Lu Y, Yin Z, Hu F, Wu W. Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles. Int J Nanomedicine. 2010:13–23.

  39. Prajapati V, Jain A, Jain R, Sahu S, Kohli DV. Treatment of cutaneous candidiasis through fluconazole encapsulated cubosomes. Drug Deliv Transl Res. 2014;4:400–8.

    Article  PubMed  CAS  Google Scholar 

  40. Muhammad AA, Pauzi NAS, Arulselvan P, Abas F, Fakurazi S. In vitro wound healing potential and identification of bioactive compounds from Moringa oleifera Lam. Biomed Res Int. 2013;2013.

  41. Muhammad AA, Arulselvan P, Cheah PS, Abas F, Fakurazi S. Evaluation of wound healing properties of bioactive aqueous fraction from Moringa oleifera Lam on experimentally induced diabetic animal model. Drug Des Devel Ther. 2016:1715–30.

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Acknowledgements

The authors are grateful to Mylan Labs, India, for providing gift sample of carvedilol phosphate. The authors thank Mohini Organics Pvt. Ltd., Mumbai, India, and BASF, Mumbai, India, for providing gift samples of glycerol monooleate and Lutrol F127, respectively. The authors are grateful to the Sophisticated Instrumentation Centre for Applied Research & Testing, Anand, India, for providing the facility of transmission electron microscopy for the analysis of cubosomes. The authors acknowledge the assistance extended by the Preclinical Research and Development Organization, Private Limited, Pune, India, for providing the facility to run experiments based on animals.

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Authors and Affiliations

  1. Department of Pharmaceutics, JSPM’s Rajarshi Shahu College of Pharmacy and Research, Tathawade, Pune, 411 033, Maharashtra, India

    Ashlesha P. Pandit, Vinit S. Kulkarni & Ujjwala Y. Kandekar

  2. Department of Pharmacology, JSPM’s Rajarshi Shahu College of Pharmacy and Research, Tathawade, Pune, 411 033, Maharashtra, India

    Vaishali M. Mute

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  1. Ashlesha P. Pandit
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  2. Vinit S. Kulkarni
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  3. Vaishali M. Mute
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  4. Ujjwala Y. Kandekar
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Contributions

Conceptualization, Ashlesha Pandit and Vinit Kulkarni; formal analysis, Vaishali Mute and Ujjwala Kandekar; methodology and investigation, Ashlesha Pandit, Vaishali Mute, and Vinit Kulkarni; writing—original draft preparation, Ashlesha Pandit and Ujjwala Kandekar; writing—review and editing, Ashlesha Pandit and Ujjwala Kandekar.

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Correspondence to Ashlesha P. Pandit.

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Pandit, A.P., Kulkarni, V.S., Mute, V.M. et al. Carvedilol-Loaded Cubosome Gel to Accelerate Wound Healing. J Pharm Innov 18, 1926–1940 (2023). https://doi.org/10.1007/s12247-023-09766-x

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