FORMULATION AND EVALUATION OF TOPICAL TRANSFEROSOMES LOADED LIDOCAINE FOR TOPICAL DELIVERY FOR BURNS, IN VITRO CHARACTERIZATION AND IN VIVO STUDY

SARMAD DHEYAA NOORI; SAMER KHALID ALI; MUSTAFA MUDHAFAR; HASAN ALI ALSAILAWI; AMIRA B. KASSEM

doi:10.22159/ijap.2025v17i4.53805

Authors

SARMAD DHEYAA NOORI College of Pharmacy-Al-Ayen Iraqi University, Thi-Qar, Iraq
SAMER KHALID ALI Department of Pharmaceutics College of Pharmacy - Al-Ayen Iraqi University, Thi-Qar, Iraq https://orcid.org/0000-0003-2493-2825
MUSTAFA MUDHAFAR Department of Medical Physics, Faculty of Medical Applied Sciences, University of Kerbala-56001, Karbala, Iraq. Department of Anesthesia Techniques and Intensive Care, Al-Taff University College-56001, Kerbala, Iraq https://orcid.org/0000-0002-3785-7396
HASAN ALI ALSAILAWI Department of basic science, Faculty of Dentistry, University of Kerbala-56001, Karbala, Iraq. Department of Anesthesia Techniques, AlSafwa University College, Karbala, Iraq
AMIRA B. KASSEM Department of Clinical Pharmacy and Pharmacy Practice. Faculty of Pharmacy, Damnhour University

DOI:

https://doi.org/10.22159/ijap.2025v17i4.53805

Keywords:

Lidocaine, Topical, Factorial design, Transferosomes, Histopathological , study

Abstract

Objective: The current investigation aimed for loading Lidocaine (LID), a local anesthetic agent, into transferosomes topically. Lidocaine has substantial first-pass metabolism results in low oral bioavailability. In order to prevent oral complications, the production of LID transferosomes was to improve LID topical distribution.

Methods: By using a 2¹.3¹ factorial design and different amounts lipids and surfactants, transferosomes formulas were created. LID transferosomes were constructed applying ethanol injection method. LID transferosomes were evaluated with regard to entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). Extra experiments were conducted on the optimum formula.

Results: Utilizing Design Expert^®, the optimum formula (F2) was evaluated, revealing EE% of 90.25±1.23%, PS of 194.50±6.50 nm, PDI of 0.602±0.0005, ZP of 50.45±1.15 mV, and amount of drug release after 6 h (Q6h) of 45.00±1.50. Further, the optimum transferosomes showed vesicles without aggregation under transmission electron microscope evaluation. In vitro release study showed that the optimum formula was released in sustained manner than LID solution. In addition, during storage, the optimum formula was stable. The histological investigation verified the safety of the optimum transferosomes.

Conclusion: The results confirmed the ability to utilize LID transferosomes for burn treatment topically.

References

Summer GJ, Puntillo KA, Miaskowski C, Green PG, Levine JD. Burn injury pain: the continuing challenge. J Pain. 2007;8(7):533-48. doi: 10.1016/j.jpain.2007.02.426, PMID 17434800.

Desai C, Wood FM, Schug SA, Parsons RW, Fridlender C, Sunderland VB. Effectiveness of a topical local anaesthetic spray as analgesia for dressing changes: a double-blinded randomised pilot trial comparing an emulsion with an aqueous lidocaine formulation. Burns. 2014;40(1):106-12. doi: 10.1016/j.burns.2013.05.013, PMID 23810271.

Verdugo Escamilla C, Alarcon Payer C, Acebedo Martinez FJ, Fernandez Penas R, Dominguez Martin A, Choquesillo Lazarte D. Lidocaine pharmaceutical multicomponent forms: a story about the role of chloride ions on their stability. Crystals. 2022;12(6):798. doi: 10.3390/cryst12060798.

Omar MM, Hasan OA, Sisi El AM. Preparation and optimization of lidocaine transferosomal gel containing permeation enhancers: a promising approach for enhancement of skin permeation. Int J Nanomedicine. 2019 Feb 26;14:1551-62. doi: 10.2147/IJN.S201356, PMID 30880964.

Choi MJ, Maibach HI. Elastic vesicles as topical/transdermal drug delivery systems. Int J Cosmet Sci. 2005;27(4):211-21. doi: 10.1111/j.1467-2494.2005.00264.x, PMID 18492190.

Home page J, Arana K. Advances in nanotechnology and their applications. Int J Pharm. 2022;12(1):4. doi: 10.37532/2249-1848-22.12.04.

Albash R, Abdelbary AA, Refai H, El Nabarawi MA. Use of transethosomes for enhancing the transdermal delivery of olmesartan medoxomil: in vitro, ex vivo, and in vivo evaluation. Int J Nanomedicine. 2019 Mar 15;14:1953-68. doi: 10.2147/IJN.S196771, PMID 30936696.

Cunha S, Costa CP, Moreira JN, Sousa Lobo JM, Silva AC. Using the quality by design (QbD) approach to optimize formulations of lipid nanoparticles and nanoemulsions: a review. Nanomedicine. 2020 Aug;28:102206. doi: 10.1016/j.nano.2020.102206, PMID 32334097.

Jankovic A, Chaudhary G, Goia F. Designing the design of experiments (DOE) an investigation on the influence of different factorial designs on the characterization of complex systems. Energy Build. 2021 Nov 1;250:111298. doi: 10.1016/j.enbuild.2021.111298.

Albash R, Badawi NM, Hamed MI, Ragaie MH, Mohammed SS, Elbesh RM. Exploring the synergistic effect of bergamot essential oil with spironolactone loaded nano-phytosomes for treatment of acne vulgaris: in vitro optimization in silico studies and clinical evaluation. Pharmaceuticals (Basel). 2023;16(1):128. doi: 10.3390/ph16010128, PMID 36678625.

Albash R, Ragaie MH, Hassab MA, El Haggar R, Eldehna WM, Al Rashood ST. Fenticonazole nitrate loaded trans novasomes for effective management of tinea corporis: design characterization in silico study and exploratory clinical appraisal. Drug Deliv. 2022;29(1):1100-11. doi: 10.1080/10717544.2022.2057619, PMID 35373684.

Refai H, El Gazar AA, Ragab GM, Hassan DH, Ahmed OS, Hussein RA. Enhanced wound healing potential of spirulina platensis nanophytosomes: metabolomic profiling molecular networking and modulation of HMGB-1 in an excisional wound rat model. Mar Drugs. 2023;21(3):149. doi: 10.3390/md21030149, PMID 36976198.

J Sheikh AA, Giri AJ, Sheikh A, Kale R, Biyani K. Nanocrystal technology characterization and pharmaceutical applications. Int J Pharm. 2021;11(11):7-12.

Mohamed HR, El Shamy S, Abdelgayed SS, Albash R, El Shorbagy H. Modulation efficiency of clove oil nano emulsion against genotoxic oxidative stress and histological injuries induced via titanium dioxide nanoparticles in mice. Sci Rep. 2024;14(1):7715. doi: 10.1038/s41598-024-57728-1, PMID 38565575.

Albash R, Abdellatif M, Hassan M, M Badawi N. Tailoring terpesomes and leciplex for the effective ocular conveyance of moxifloxacin hydrochloride (comparative assessment): in vitro, ex-vivo, and in vivo evaluation. Int J Nanomedicine. 2021 Aug 3;16:5247-63. doi: 10.2147/IJN.S316326, PMID 34376978.

Eltabeeb MA, Hamed RR, El Nabarawi MA, Teaima MH, Hamed MI, Darwish KM. Nanocomposite alginate hydrogel loaded with propranolol hydrochloride kolliphor® based cerosomes as a repurposed platform for methicillin-resistant staphylococcus aureus (mrsa) induced skin infection; in vitro, ex vivo, in silico, and in vivo evaluation. Drug Deliv Transl Res. 2025;15(2):556-76. doi: 10.1007/s13346-024-01611-z, PMID 38762697.

Teaima MH, Eltabeeb MA, El Nabarawi MA, Abdellatif MM. Utilization of propranolol hydrochloride mucoadhesive invasomes as a locally acting contraceptive: in vitro ex-vivo, and in vivo evaluation. Drug Deliv. 2022;29(1):2549-60. doi: 10.1080/10717544.2022.2100514, PMID 35912869.

Aziz DE, Abdelbary AA, Elassasy AI. Investigating superiority of novel bilosomes over niosomes in the transdermal delivery of diacerein: in vitro characterization ex vivo permeation and in vivo skin deposition study. J Liposome Res. 2019;29(1):73-85. doi: 10.1080/08982104.2018.1430831, PMID 29355060.

Mendes AC, Gorzelanny C, Halter N, Schneider SW, Chronakis IS. Hybrid electrospun chitosan phospholipids nanofibers for transdermal drug delivery. Int J Pharm. 2016;510(1):48-56. doi: 10.1016/j.ijpharm.2016.06.016, PMID 27286632.

Ezzat SM, Salama MM, ElMeshad AN, Teaima MH, Rashad LA. HPLC–DAD–MS/MS profiling of standardized rosemary extract and enhancement of its anti-wrinkle activity by encapsulation in elastic nanovesicles. Arch Pharm Res. 2016;39(7):912-25. doi: 10.1007/s12272-016-0744-6, PMID 27107862.

Roberts MS, Mohammed Y, Pastore MN, Namjoshi S, Yousef S, Alinaghi A. Topical and cutaneous delivery using nanosystems. J Control Release. 2017 Feb 10;247:86-105. doi: 10.1016/j.jconrel.2016.12.022, PMID 28024914.

Hathout RM, Elshafeey AH. Development and characterization of colloidal soft nano carriers for transdermal delivery and bioavailability enhancement of an angiotensin II receptor blocker. Eur J Pharm Biopharm. 2012;82(2):230-40. doi: 10.1016/j.ejpb.2012.07.002, PMID 22820090.

Salama AH, Aburahma MH. Ufasomes nano vesicles based lyophilized platforms for intranasal delivery of cinnarizine: preparation optimization ex vivo histopathological safety assessment and mucosal confocal imaging. Pharm Dev Technol. 2016;21(6):706-15. doi: 10.3109/10837450.2015.1048553, PMID 25996631.

Sun Z, Nicolosi V, Rickard D, Bergin SD, Aherne D, Coleman JN. Quantitative evaluation of surfactant stabilized single-walled carbon nanotubes: dispersion quality and its correlation with zeta potential. J Phys Chem C. 2008;112(29):10692-9. doi: 10.1021/jp8021634.

Albash R, Abdelbari MA, Elbesh RM, Khaleel EF, Badi RM, Eldehna WM. Sonophoresis mediated diffusion of caffeine loaded transcutol® enriched cerosomes for topical management of cellulite. Eur J Pharm Sci. 2024 Oct 1;201:106875. doi: 10.1016/j.ejps.2024.106875, PMID 39121922.

El Naggar MM, El Nabarawi MA, Teaima MH, Hassan M, Hamed MI, Elrashedy AA. Integration of terpesomes loaded levocetrizine dihydrochloride gel as a repurposed cure for methicillin-resistant staphylococcus aureus (mrsa) induced skin infection; d-optimal optimization ex vivo, in silico, and in vivo studies. Int J Pharm. 2023 Feb 25;633:122621. doi: 10.1016/j.ijpharm.2023.122621, PMID 36693486.

Albash R, El Nabarawi MA, Refai H, Abdelbary AA. Tailoring of PEGylated bilosomes for promoting the transdermal delivery of olmesartan medoxomil: in vitro characterization ex vivo permeation and in vivo assessment. Int J Nanomedicine. 2019 Aug;14:6555-74. doi: 10.2147/IJN.S213613, PMID 31616143.

Abdellatif MM, Eltabeeb MA, El Nabarawi MA, Teaima MH. A review on advances in the development of spermicides loaded vaginal drug delivery system: state of the art. Int J App Pharm. 2022;14(4):48-54. doi: 10.22159/ijap.2022v14i4.44925.

Abdellatif MM, Khalil IA, Khalil MA. Sertaconazole nitrate loaded nanovesicular systems for targeting skin fungal infection: in vitro, ex-vivo and in vivo evaluation. Int J Pharm. 2017;527(1-2):1-11. doi: 10.1016/j.ijpharm.2017.05.029, PMID 28522423.

Karna S, Chaturvedi S, Agrawal V, Alim M. Formulation approaches for sustained release dosage forms: a review. Asian J Pharm Clin Res. 2015;8(5):46-53.

Zeb A, Qureshi OS, Kim HS, Cha JH, Kim HS, Kim JK. Improved skin permeation of methotrexate via nanosized ultra-deformable liposomes. Int J Nanomedicine. 2016 Aug 8;11:3813-24. doi: 10.2147/IJN.S109565, PMID 27540293.

Priyanka K, Singh S. A review on skin targeted delivery of bioactives as ultra deformable vesicles: overcoming the penetration problem. Curr Drug Targets. 2014;15(2):184-98. doi: 10.2174/1389450115666140113100338, PMID 24410447.