Skip to main content Skip to main navigation menu Skip to site footer

A nano-enclatherated-gel-composite for the treatment of alcohol abuse and addiction

  • Fatema Mia
  • Mershen Govender
  • Sunaina Indermun
  • Pradeep Kumar
  • Lisa C. du Toit
  • Yahya E. Choonara


Alcoholism is a highly prevalent disease, with successful rehabilitation being poor due to irrepressible cravings that result in relapse. This study developed and analysed an intramuscular injection capable of providing a sustained release of disulfiram over one month. Statistically optimized disulfiram-loaded nanomicelles were prepared and incorporated into a thermosensitive gel resulting in a nano-enclatherated-gel-composite (NEGC). The nanomicelle system demonstrated a drug loading capacity and entrapment efficiency of 33.66% and 50.98%, respectively, with a sustained release of 65% of the administered disulfiram achieved after 28 days through the thermosensitive hydrogel. Additionally, ex vivo release studies have been undertaken using rat muscle tissue with in vivo biodistribution, plasma levels, histopathology and myotoxicity following oral disulfiram administration and intramuscular NEGC administration also assessed in Sprague-Dawley rats. Results obtained in this study have indicated that the designed delivery system has the potential to successfully release disulfiram in a sustained manner for the treatment of alcohol abuse.



  1. WHO, 2018. Global status report on alcohol and health. (accessed 01 September 2021).
  2. Chen X, Zhang L, Hu X, Lin X, Zhang Y, Tang X. Formulation and preparation of a stable intravenous disulfiram‐loaded lipid emulsion. Eur J Lipid Sci. Technol. 2015;117(6):869-78. doi:10.1002/ejlt.201400278.
  3. Lu J, Huang Y, Zhao W, Marquez RT, Meng X, Li J, et al. PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers. Biomaterials 2013;34(5):1591-1600. doi: 10.1016/j.biomaterials.2012.10.073.
  4. Kulhari H, Pooja D, Shrivastava S, Telukutala SR, Barui AK, Patra CR, et al. Cyclic-RGDfK peptide conjugated succinoyl-TPGS nanomicelles for targeted delivery of docetaxel to integrin receptor over-expressing angiogenic tumours. Nanomedicine 2015;11(6):1511-20. doi:10.1016/j.nano.2015.04.007.
  5. Ricci EJ, Lunardi LO, Nanclares DMA, Marchetti JM. Sustained release of lidocaine from Poloxamer 407 gels. Int J Pharm. 2005;288(2):235-44. doi:10.1016/j.ijpharm.2004.09.028.
  6. Brazeau GA, Fung HL. An in vitro model to evaluate muscle damage following intramuscular injections. Pharm Res. 1989;6(2):167-70. doi:10.1023/a:1015940811827.
  7. Diogo LN, Faustino IV, Afonso RA, Pereira SA, Monteiro EC, Santos AI. Voluntary Oral Administration of Losartan in Rats. J Am Assoc Lab Anim Sci. 2014;54(5):549-56.
  8. Brancaccio P, Lippi G, Maffulli N. Biochemical markers of muscular damage. Clin Chem Lab Med. 2010;48(6):757-67. doi:10.1515/CCLM.2010.179.
  9. Butt AM, Amin MCIM, Katas H, Sarisuta N, Witoonsaridsilp W, Benjakul R. In vitro characterization of pluronic F127 and D-α-tocopheryl polyethylene glycol 1000 succinate mixed micelles as nanocarriers for targeted anticancer-drug delivery. J Nanomater. 2012;916573. doi:10.1155/2012/916573.
  10. Goldberg M, Langer R, Jia X. Nanostructured materials for applications in drug delivery and tissue engineering. J Biomater Sci Polym Ed. 2007;18(3):241-68. doi:10.1163/156856207779996931.
  11. Kumar R, Aadil KR, Mondal K, Mishra YK, Oupicky D, Ramakrishna S, Kaushik A. Neurodegenerative disorders management: state-of-art and prospects of nano-biotechnology. Crit Rev Biotechnol. 2021;25:1-33. doi: 10.1080/07388551.2021.1993126.
  12. Nehra M, Uthappa UT, Kumar V, Kumar R, Dixit C, Dilbaghi N, Mishra YK, Kumar S, Kaushik A. Nanobiotechnology-assisted therapies to manage brain cancer in personalized manner. J Control Release. 2021;338:224-43. doi: 10.1016/j.jconrel.2021.08.027.
  13. Kaushik A, Jayant RD, Bhardwaj V, Nair M. Personalized nanomedicine for CNS diseases. Drug Discov Today. 2018;23(5):1007-15. doi: 10.1016/j.drudis.2017.11.010.
  14. Mi Y, Zhao J, Feng SS. Vitamin E TPGS prodrug micelles for hydrophilic drug delivery with neuroprotective effects. Int J Pharm. 2012;438(1):98-106. doi:10.1016/j.ijpharm.2012.08.038.
  15. Mu L, Elbayoumi TA, Torchilin VP. Mixed micelles made of poly (ethylene glycol)–phosphatidylethanolamine conjugate and d-α-tocopheryl polyethylene glycol 1000 succinate as pharmaceutical nanocarriers for camptothecin. Int J Pharm. 2005;306(1):142-9. doi:10.1016/j.ijpharm.2005.08.026.
  16. Duan X, Xiao J, Yin Q, Zhang Z, Yu H, Mao S, Li Y. Multi-targeted inhibition of tumor growth and lung metastasis by redox-sensitive shell crosslinked micelles loading disulfiram. Nanotechnology. 2014;25(12):125102. doi:10.1088/0957-4484/25/12/125102.
  17. Miao L, Su J, Zhuo X, Luo L, Kong Y, Gou J, Yin T, Zhang Y, He H, Tang X. mPEG5k-b-PLGA2k/PCL3.4k/MCT Mixed Micelles as Carriers of Disulfiram for Improving Plasma Stability and Antitumor Effect in Vivo. Mol. Pharm. 2018;15(4):1556-64. doi:10.1021/acs.molpharmaceut.7b01094.
  18. Kojarunchitt T, Hook S, Rizwan S, Radesa T, Baldursdottir S. Development and characterization of modified poloxamer 407 thermoresponsive depot systems containing cubosomes. Int J Pharm. 2011;408(1):20-6. doi:10.1016/j.ijpharm.2011.01.037.
  19. Avachat AM, Kapure SS. Asenapine maleate in situ forming biodegradable implant: An approach to enhance bioavailability. Int J Pharm. 2014;477(1):64-72. doi:10.1016/j.ijpharm.2014.10.006
  20. Kapoor DN, Katare OP, Dhawan S. In situ forming implant for controlled delivery of an anti-HIV fusion inhibitor. Int J Pharm. 2012;426(1):132-143. doi: 10.1016/j.ijpharm.2012.01.005.
  21. Saracino MA, Marcheselli C, Somaini L, Gerra G, De Stefano F, Pieri MC, et al. Simultaneous determination of disulfiram and bupropion in human plasma of alcohol and nicotine abusers. Anal Bioanal Chem. 2010;398(5):2155-61. doi:10.1007/s00216-010-4172-z.
  22. Hegde A, Singh SM, Sarkar S. Long-acting Preparations in Substance Abuse Management: A Review and Update. Indian J Psychol Med. 2013;35(1):10-18. doi:10.4103/0253-7176.112194.
  23. Rungseevijitprapa W, Brazeau GA, Simkins JW, Bodmeier R. Myotoxicity studies of O/W-in situ forming microparticle systems. Eur J Pharm Biopharm. 2008;69(1):126-33. doi:10.1016/j.ejpb.2007.10.009.
  24. Surber C, Sucker H. Tissue tolerance of intramuscular injectables and plasma enzyme activities in rats. Pharm Res. 1987;4(6):490-4. doi:10.1023/a:1016427605545.
  25. Sluka KA, Kalra A, Moore SA. Unilateral intramuscular injections of acidic saline produce a bilateral, long-lasting hyperalgesia. Muscle Nerve 2001;24:37-46. doi:10.1002/1097-4598(200101)24:1<37::aid-mus4>;2-8.
  26. Thuilliez C, Dorso L, Howroyd P, Gould S, Chanut F, Burnett R. Histopathological lesions following intramuscular administration of saline in laboratory rodents and rabbits. Exp Toxicol Pathol. 2009;61(1):13-21. doi:10.1016/j.etp.2008.07.003.

How to Cite

Mia, F. ., Govender, M. ., Indermun, S. ., Kumar, P. ., Toit, L. C. du ., & Choonara, Y. E. . (2022). A nano-enclatherated-gel-composite for the treatment of alcohol abuse and addiction. Nanofabrication, 7, e002.




Article Details

Most Read This Month


Copyright (c) 2022 Fatema Mia, Mershen Govender, Sunaina Indermun, Pradeep Kumar, Lisa C. du Toit, Yahya E. Choonara

Creative Commons License

This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.