COMPARATIVE STUDY OF ETHOSOMES AND PHARMACOSOMES AS A PROMISING APPROACH FOR IMPROVING DAPSONE AND CLOXACILLINE TRANSDERMAL ANTI LEPROTIC ACTIVITY: IN VITRO AND IN VIVO STUDIES

PRIYANKA MAURYA; TAPASVI GUPTA; RITU GILHOTRA

doi:10.22159/ijap.2026v18i2.57081

Authors

PRIYANKA MAURYA Suresh Gyan Vihar University, Jaipur, Rajasthan, India
TAPASVI GUPTA Suresh Gyan Vihar University, Jaipur, Rajasthan, India
RITU GILHOTRA Suresh Gyan Vihar University, Jaipur, Rajasthan, India

DOI:

https://doi.org/10.22159/ijap.2026v18i2.57081

Keywords:

Vesicles, Transdermal delivery, Ethosomal gel, Encapsulation studies, Drug diffuse study, Stability

Abstract

Objective: This study aimed to develop and evaluate a vesicular gel system for the topical delivery of Dapsone and Cloxacillin with the goal of enhancing drug permeation, sustaining release within the skin, and improving wound healing efficacy.

Methods: Gel were prepared and characterized for particle size, (PDI) Polydispersity index, zeta potential, and encapsulation efficiency. Optimized formulations F3 and P5 were further subjected to (FTIR) Fourier transform infrared spectroscopy, (SEM) Scanning electron microscopy, and (TEM) Transmission electron microscopy analyses to confirm FTIR and vesicle morphology. In vitro drug release of G3 & G5, skin irritation testing, stability studies, and in vivo wound healing evaluations were performed.

Results: F3 and P5 showed favorable Nano scale vesicle characteristics (116.3 nm and 110.6 nm; PDI: 0.32 and 0.36; zeta potential: –21.7 mV and –30.6 mV; encapsulation efficiency: 71.91% and 73.95%). The gels G3 and G5 demonstrated desirable physicochemical properties (pH ~7.0, high drug content of 76.88% and 83.54%, viscosity 45.223 cps and 40.154 cps, and superior spreadability). In vitro release studies confirmed biphasic sustained release, with G3 showing the highest cumulative release (88.68% over 24 hours). Stability studies indicated no changes in physicochemical properties after 3 months. Skin irritation tests confirmed biocompatibility, and in vivo experiments demonstrated superior wound healing with ethosomal gels, particularly G3, as evidenced by morphological and histological studies.

Conclusion: The ethosomal gel system, especially G3, offers significant potential as a topical carrier for Dapsone and Cloxacilline, with enhanced penetration, sustained release, stability, safety, and superior wound healing efficacy compared to conventional formulations.

References

1. Jain S, Jain P, Umamaheshwari RB, Jain NK. Transfersomes—a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation. Drug DevInd Pharm. 2023 Aug ; 29(9): 1013-1026. https://doi.org/10.1081/DDC-120025458.

2. Verma DD, Verma S, Blume G, Fahr A. Particle size of liposomes influences dermal delivery of substances into skin. Int J Pharm. 2020 Jun; 258(2): 141-151. https://doi.org/10.1016/s0378-5173(03)00183-2.

3. Panchagnula R, Sharma P. Transdermal delivery of nifedipine: IV. Influence of penetration enhancers on the in vitro permeation of nifedipine through rat skin. Pharm ActaHelv. 2016;73(2):67-74. https://doi.org/10.1016/S0378-5173(98)00110-0.

4. Cevc G, Blume G. Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. BiochimBiophysActa. 1992 Feb; 1104(1): 226-232. https://doi.org/10.1016/0005-2736(92)90154-e.

5. Cevc G, Gebauer D, Stieber J, Schätzlein A, Blume G. Ultraflexible vesicles, transfersomes, have an extremely low pore penetration resistance and transport therapeutic amounts of insulin across the intact mammalian skin. Biochim BiophysActa. 2018 Jan; 1368(2): 201-215. https://doi.org/10.1016/s0005-2736(97)00177-6.

6. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 2022 Aug; 13(1): 238-252. https://doi.org/10.1016/s0022-2836(65)80093-6.

7. Bwalya A. Witika, Larry L. Mweetwa, Kabo O. Tshiamo, Karen Edler, Scott K. Matafawali, Pascal V. Ntemi, Melissa T. R. Chikukwa and Pedzisai A. Makoni, Vesicular drug delivery and targeting: challenges and future prospects. Journal of Pharmacy and Pharmacology. 2017 Jun; XX: 1-15. https://doi.org/10.1093/jpp/rgab082.

8. E. Molinelli, M. Paolinelli, A. Campanati, V. Brisigotti, A. Offidani, Metabolic, pharmacokinetic, and toxicological issues surrounding Dapsonesone, ExpetOpin. Drug Metabol. Toxicol, 2019 Apr; 15(5): 367–379. https://doi.org/10.1080/17425255.2019.1600670.

9. I.M. Bernades Goulart, G. Leonel Arbex, M. Hubaide Carneiro, M. Scalia Rodrigues, R. Gadia, Efeitos adversos da poliquimioterapia empacientes com hanseníase: um levantamento de cincoanosem um Centro de Saude da Universidade Federal de Uberlandia, Rev. Soc. Bras. Med. Trop. 2002 Oct; 35: 453–460. https://doi.org/10.1590/S0037-86822002000500005.

9. Barry BW. Mode of action of penetration enhancers in human skin. J Control Release. 2021 Dec; 6(1): 85-97. https://doi.org/10.1016/0168-3659(87)90066-6.

10. Puri A, Loomis K, Smith B, et al. Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic. Crit Rev Ther Drug Carrier Syst. 2010 June; 26(6): 523-580. https://doi.org/10.1615/critrevtherdrugcarriersyst.v26.i6.10.

11. Ali M. Nasr, Fayrouz Moftah, Mohammed A. S. Abourehab and Shadeed Gad, Design, Formulation, and Characterization of Valsartan Nanoethosomes for Improving Their Bioavailability, Pharmaceutics 2022 Oct, 14(11), 2268, 2-25. https://doi.org/10.3390/pharmaceutics14112268.

12. Hanumant Alias AbhishekGarg, Reena Sheoran1, NeelamPawar, Sanjeev, Rahul, Formulation And Evaluation of Miconazole Pharmacosome by Using Solvent Evaporation Method to Enhance Solubility of Miconazole, International Journal of Membrane Science and Technology, 2023 Aug; 10(4): 2362-2373. https://doi.org/10.48047/chthkp23.

13. NaseebBashaShaik, Shakuntala Devi Mortha, Lakshmi PKand LathaKukati, Formulation and evaluation of tizanidine hydrochloride loaded ethosomes for transdermal delivery; J. Pharm. Sci. & Res.2020 Sept; 12(11): 1400-1410. https://doi.org/10.1016/j.molliq.2024.125111.

14. Nimisha, Zeeshan Fatima, Chanchal Deep Kaur, Formulation and performance of berberisaristata extract loaded ethosomal gel Asian Journal of Pharmaceutic, 2017 Sept; 11(3), 176-183. https://doi.org/10.22377/ajp.v11i03.1401.

15. T. S. saraswathi, r. roshini, n. damodharan, m. mothilal, s. k. janani, Development of lipid-based vesicles of terbinafine gel for skin delivery by 32 full factorial design, Int J App Pharm, 2024 July, 16(4), 231-243. https://doi.org/10.22159/ijap.2024v16i4.50460.

16. K. Anju, SnehPriya, D. S. Sandeep, PrashantNayak, Pankaj Kumar, Abhishek Kumar, Cynthia Lizzie Lobo1and S. P. Krithi, Formulation and Optimization of Zaltoprofen Loaded Ethosomal Gel by using 23Full Factorial Designs, ournal of Pharmaceutical Research International, 2021 April; 33(24B): 30-44. https://doi.org/10.9734/jpri/2021/v33i24B31439.

17. Ruchi Tiwari ,Gaurav Tiwari, Ankita Wal and Chitranshu Gupta, Liposomal delivery of 5 Fluorouracil and Tretinoin: An Aspect of Topical treatment of skin warts; Ars Pharm. 2019 May; 60(3): 139-146. http://dx.doi.org/10.30827/ars.v60i3.7966.

18. S. Ramkanth a, C. Madhusudhana Chetty b, Y. Sudhakar c, V.S. Thiruvengadarajan a, P. Anitha a, C. Gopinath, Development, characterization & amp: invivo evaluation of proniosomal based transdermal delivery system of Atenolol, Future Journal of Pharmaceutical Sciences, 2018 June; 4(1): 80-87. https://doi.org/10.1016/j.fjps.2017.10.003.

19. Prashant Halagali, Vishal I Wannur, Abishek Kumar A Patil, Vaibhavi D. Torgal, Shrikrishna M Naik, Santosh A Marennavar, Sakshi Shahapurmath, PankajPatil, Formulation and Evaluation of Quercetin Ethosomal Hydrogel for Topical Delivery System, Int. J. Pharm. Investigation, 2024 July; 14(3):749-758. https://doi.org/10.5530/ijpi.14.3.84.

20. AshutoshTiwari , Puja Bag, Mrinmoy Sarkar , VineyChawla, and Pooja A. Chawla, Formulation, validation and evaluation studies on metaxalone and diclofenac potassium topical gel, Environmental Analysis Health and Toxicology 2021 Mar; 36(1): 1-8. https://doi.org/10.5620/eaht.2021001.

21. Mehwish Andleeb , Haij Muhammad Shoaib Khan, Muhammad Daniyal, Development, Characterization and stability Evaluation of Topical Gel Loded with Ethosomes Containig Achillea nillefolium L. Extract, Frontriers in Pharmacology, 2021 April; 12(1): 01–11. https://doi.org/10.3389/fphar.2021.603227.

22. AshutoshTiwari , Puja Bag, MrinmoySarkar, VineyChawla, and Pooja A. Chawla, Formulation, validation and evaluation studies on metaxalone and diclofenac potassium topical gel, Environmental Analysis Health and Toxicology 2021 Jan; 36(1): 1-8. https://doi.org/10.5620/eaht.2021001.

23. SnehPriya, PreethikaShridhar, KshemaShekharaSusheela, ShentharSuraksha, K. Kudva, Tolnaftate-Loaded Ethosomal Gel for Topical Delivery: Formulation and In Vitro Evaluation, Journal of Health and Allied Sciences, 2024 June; 15(1): 26-31. https://doi.org/10.1055/s-0044-1787293.

24. Syed Ahmed Iizhar, Ismail Ahmed Syed , RukhsanaSatar , Shakeel Ahmed Ansari, In vitro assessment of pharmaceutical potential of ethosomes entrapped with terbinafine hydrochloride, Journal of Advanced Research 2016 March; 7 : 453–461. http://dx.doi.org/10.1016/j.jare.2016.03.003.

25. Xingyan Liu, Hong Liu, Jianqiang Liu, Zhiwei He, Congcong Ding, Guoliang Huang, Weihua Zhou, Leshan Zhou, Preparation of a ligustrazine ethosome patch and its evaluation in vitro and in vivo, International Journal of Nanomedicine 2011 Jan; 6 : 241–247. https://doi.org/10.2147/IJN.S16044.

26. Hadeer A. EI. Hashemy, Design, formulation and optimization of topical ethosomes using full factorial design: in-vitro and ex-vivo characterization, 2022 March; 32(1): 74-82. https://doi.org/10.1080/08982104.2021.1955925.

27. Jianzhong Wang, Zhiyuan Li , Feifei Sun, Shus heng Tang, Suxia Zhang, Pengyyue Lv, Jing Li, Xingyuan Cao, Evaluation of dermal irritation and skin sensitization due to vitacoxib, 2017 Jun; 4 :287–290. https://doi.org/10.1016/j.toxrep.2017.06.003.

28. DR. Pankajnainwal, Perform Skin Irritation Study Of The Developed Formulation, Nat. Volatiles &Essent. Oils, 2020 Jan; 7(1): 86-95. https://doi.org/10.52783/nveo.5451.

29. Hoseok Jung , WookcheolSeo , TaeseongJeong , Hyung Won Kang , Sungchul Kim, A Study on the Skin Irritation Toxicity Test of Processed Sulfur in New Zealand White Rabbit, Journal of Pharmacopuncture 2022 March; 25(1): 46-51. https://doi.org/10.3831/KPI.2022.25.1.46.

30. Marcell de melo naves fla, Vioaugusto del faveriribeiro, Lucas gomespatrocinio, Jose´ antoniopatrocinio, Raul negra o fleury & isabelamariabernardesgoulart, Bacterial load in the nose and its correlation to the immune response in leprosy patients, Lepr Rev 2013 March; 84(1), 85–91. https://doi.org/10.47276/lr.84.1.85.

31. Suvernkar Suparna Vishwanath , Vishal Rajput, Deepa Rajput, NitinWathore, A study of clinico-histopathological correlation in leprosy, IP Archives of Cytology and Histopathology Research 2022 Nov; 7(3): 164–170. https://doi.org/10.18231/j.achr.2022.036.

32. Rajappa Margret Chandira, Palanisamy Pethappachetty, GnanasekeranChandiran, Dominic Antony Samy, Formulation and Evaluation of Nanosponges of an Antileprosy Drug: Topical Application, Asian Journal of Biological and Life Sciences, 2022 Aug; 11(2): 554-563. http://dx.doi.org/10.5530/ajbls.2022.11.75.

33. Debasis Nayak, Yugal Kishore ohanta, Pradipta Ranjan Rauta, Ishani Chakrabartty & Muthupandian Saravanan, Ethosomes for Dermal and Transdermal Drug Delivery Systems, Pharmaceutical Nanobiotechnology and targeted therapy 2022 Oct; 10(7): 313-336. https://doi.org/10.1007/978-3-031-12658-1_11.

34. Jamal MoideenMuthu, Mohamed Barkat A Khan , VijayaRajendran , Mohamed El-Sherbiny, Gamal Othman, Abdulrahman Bashir Ahmed Hussamuldin, RashaHamed Al-Serwi, Polymeric ethosomal gel loaded with nimodipine: Optimisation, pharmacokinetic and histopathological analysis, 2022 Nov; 30(11): 1603-1611. https://doi.org/10.1016/j.jsps.2022.09.003.

35. Ahlam Zaid Alkilani, Rania Hamed, HajerAbdo, LubnaSwellmeen, Haneen A. Basheer, WalaaWahdan, and Amani D. Abu Kwiak, Formulation and Evaluation of Azithromycin-Loaded Niosomal Gel: Optimization, In Vitro Studies, Rheological Characterization, and Cytotoxicity Study, n ACS Omega, 2022, 7(44): 39782–39793. https://doi.org/10.1021/acsomega.2c03762.

36. Teja kumar ponduri, Chakravarthi guntupalli , Balamurugan jeganathan, Narender malothu, Impact of ligand conjugation of physicochemical attributes of polymeric nanoparticles of atypical antipsychotic drug for nose-to-brain delivery, Int J App Pharm, 2024 Nov, 16(6) : 38-47. https://doi.org/10.22159/ijap.2024v16i6.52003.

37. Jadhav shivraj popet, Dhakad Prashant kumar, Gupta Tapsvi, Gilhotra Ritu, Formulation development and evaluation of paliperidonenanosuspension for solubility enhancement, Int J App Pharm, 2024 May; 16(4): 173-181. https://dx.doi.org/10.22159/ijap.2024v16i4.51218.