Formulation and Evaluation of Niosomes of Clopidogrel for the Treatment of Peripheral Artery Disease
DOI:
https://doi.org/10.63682/jns.v14i32S.7872Keywords:
Clopidogrel, Niosomes, Peripheral Artery Disease, Nanocarrier, Thin Film Hydration, Drug DeliveryAbstract
Peripheral Artery Disease (PAD) is a progressive vascular condition that significantly elevates the risk of thrombotic events. Clopidogrel, a widely used antiplatelet agent, is limited by systemic side effects and poor bioavailability. This study focuses on the formulation and evaluation of Clopidogrel-loaded niosomes to enhance therapeutic efficacy through improved encapsulation, stability, and controlled release. Among the developed formulations, the optimized niosomal formulation (F2) demonstrated high drug entrapment efficiency (94.60 ± 16.90% initially and 89.47 ± 2.50% after 3 months), indicating excellent drug loading capability. In vitro drug release studies revealed a sustained and controlled release profile, with F2 releasing 3.22 ± 0.38 mg (approximately 39% of the total drug load) of Clopidogrel over 24 hours, outperforming F3, which released only 2.50 ± 0.64 mg (15%). Stability studies confirmed the physical robustness of F2, with no significant change (p > 0.05) in vesicle size or entrapment efficiency over a 3-month period at 4 °C, unlike F1 and F3, which exhibited significant increases in particle size. The nanoscale vesicle size of F2, maintained through a balanced 1:1 cholesterol-to-surfactant ratio, contributed to its enhanced stability and drug release properties. The optimized surfactant composition improved vesicle rigidity and integrity, essential for prolonged release and targeted delivery. Importantly, the encapsulation of Clopidogrel in niosomes may reduce systemic side effects such as gastrointestinal irritation, offering a promising alternative to conventional formulations for the effective management of PAD.
Downloads
Metrics
References
Serruys PW, Morice M-C, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360:961–72.
Kulik A, Ruel M, Jneid H, Ferguson TB, Hiratzka LF, Ikonomidis JS, et al. Secondary prevention after coronary artery bypass graft surgery. Circ. 2015;131:927–64.
Usman MRM, Ghuge PR, Jain B. Niosomes: A novel trend of drug delivery. Eur J Biomed Pharm Sci. 2017;4:436–42.
Marianecci C, Di Marzio L, Rinaldi F, Celia C, Paolino D, Alhaique F, et al. Niosomes from 80s to present: The state of the art. Adv Colloid Interface Sci. 2014;205:187–206.
Parashar AK, Hardenia A, Saraogi GK, et al. Next-Generation Nucleic Acid Delivery: A Review of Nanobiosystem Design and Applications. Curr Gene Ther. 2025;25:1–19. doi:10.2174/0115665232367377250519114910.
Shete MB, Saraogi GK, Parashar AK. Dengue fever: A comprehensive review of diagnosis and management. Antiinfect Agents. 2025;23. Available from: http://dx.doi.org/10.2174/0122113525366277250306072415
Parashar AK, Saraogi GK, Jain PK, Kurmi B, Shrivastava V, Arora V. Polymer-drug conjugates: revolutionizing nanotheranostic agents for diagnosis and therapy. Discov Oncol. 2024;15(1). Available from: http://dx.doi.org/10.1007/s12672-024-01509-9
Gulati P, Chandila V, Parashar AK, Sethi VA. A review on advancements in lipid-based nanoparticles for vaccine adjuvant and antigen delivery. ijnrph. 2024;26–34. Available from: http://dx.doi.org/10.61554/ijnrph.v2i2.2024.128
Sareen T, Parashar AK, Tyagi LK. Exploring the unique role of albumin as a carrier in nanomedicine-based drug delivery. ijnrph. 2024;129–37. Available from: http://dx.doi.org/10.61554/ijnrph.v2i2.2024.127
Vallières K, Laterreur V, Tondreau MY, Ruel J, Germain L, Fradette J, et al. Human adipose-derived stromal cells for the production of completely autologous self-assembled tissue-engineered vascular substitutes. Acta Biomater. 2015;24:209–19.
Parashar AK, Sethi VA. Polymer Nanoparticles for Cancer Immunotherapy: Preparation Methods and Applications. Nat Cell Sci. 2024;2(2):95–105. Available from: https://doi.org/10.61474/ncs.2024.0001229. Mensah GA, Roth GA, Fuster V. The global burden of cardiovascular diseases and risk factors. J Am Coll Cardiol. 2019;74:2529–32.
Evans NS, Solomon AL, Ratchford EV. Vascular Disease Patient Information Page: Peripheral artery disease - 2025 update. Vasc Med [Internet]. 2025;1358863X251320917. Available from: http://dx.doi.org/10.1177/1358863X251320917
Mawazi SM, Ge Y, Widodo RT. Niosome preparation techniques and structure-an illustrated review. Pharmaceutics [Internet]. 2025;17(1):67. Available from: http://dx.doi.org/10.3390/pharmaceutics17010067
Parashar AK, Tyagi LK, Sethi VA. Histotripsy: A Promising Modality for Cancer Treatment. Curr Cancer Ther Rev. 2024 Sep 19;21. Available from: https://doi.org/10.2174/0115733947330950240906075443
Vyas LK, Tapar KK, Nema RK, Parashar AK. Development and Characterization of Topical Liposomal Gel Formulation for Anti-Cellulite Activity. Int J Pharm Pharm Sci. 2013;5:512–16.
Archana, Yallapragada SSC, Pawar S, Sathvika, Gotham S. Formulation, evaluation, and characterization of Indapamide niosomes. Fut J Pharm & H Sci [Internet]. 2024;4(2):68–77. Available from: http://dx.doi.org/10.26452/fjphs.v4i2.609
Shaik AP, Naidu V. Formulation, evaluation and characterization of hydrochlorothiazide niosomes. Fut J Pharm & H Sci [Internet]. 2024;4(1):69–79. Available from: http://dx.doi.org/10.26452/fjphs.v4i1.566
Adhami M, Picco CJ, Detamornrat U, Anjani QK, Cornelius VA, Robles-Martinez P, et al. Clopidogrel-loaded vascular grafts prepared using digital light processing 3D printing. Drug Deliv Transl Res [Internet]. 2024;14(6):1693–707. Available from: http://dx.doi.org/10.1007/s13346-023-01484-8
Tyagi R, Waheed A, Kumar N, Ahad A, Bin Jardan YA, Mujeeb M, et al. Formulation and evaluation of plumbagin-loaded niosomes for an antidiabetic study: Optimization and in vitro evaluation. Pharmaceuticals (Basel) [Internet]. 2023;16(8). Available from: http://dx.doi.org/10.3390/ph16081169
Jansen S, Teraa M, Chan N, Bosch J, de Borst GJ, Hinchliffe R, et al. Assessing limb outcomes in drug trials in peripheral artery disease: The need for a universal and pragmatic definition. Eur J Vasc Endovasc Surg [Internet]. 2023;66(3):442–3. Available from: http://dx.doi.org/10.1016/j.ejvs.2023.06.007
Parashar AK, Gupta AK, Jain NK. Synthesis and characterization of Agiopep-2 anchored PEGylated polypropyleneimine dendrimers for targeted drug delivery to glioblastoma multiforme. JDDT Online. 2018;8(6):74–79.
Cakir N, Ozturk N, Kara A, Zarrabi A, Mustafaoglu N. Optimizing niosome formulations for enhanced cellular applications: A comparative case study with L-α-lecithin liposomes [Internet]. bioRxiv. 2023. Available from: http://dx.doi.org/10.1101/2023.11.14.567080
Shi L, Chen X, Wang H, Xu Y, Din S, Liu J, et al. Systemic delivery of clopidogrel inhibits neointimal formation in a mouse vein graft model. J Cardiovasc Pharmacol [Internet]. 2022;80(6):832–41. Available from: http://dx.doi.org/10.1097/FJC.0000000000001361
Parashar AK, Patel P, Gupta AK, Kurmi BD. Synthesis, Characterization, and in vivo Evaluation of PEGylated PPI Dendrimer for Safe and Prolonged Delivery of Insulin. Drug Deliv Lett. 2019;9(3):248–63. Available from: http://dx.doi.org/10.2174/2210303109666190401231920
Adella A, Yamsani SK. Formulation and In vivo studies of Clopidogrel by Self-Nanoemulsifying Drug Delivery System. Int J Pharm Sci Drug Res [Internet]. 2021;13(05):479–87. Available from: http://dx.doi.org/10.25004/ijpsdr.2021.130504
Kapil MJ, Deka D, Lahkar M, Sharma N, Sarma D, Kalita P, et al. Formulation, optimization and evaluation of niosomes containing leaf extract of Moringa oleifera and pharmacological screening of the extract against Rheumatoid Arthritis. J Pharm Res Int [Internet]. 2021;236–45. Available from: http://dx.doi.org/10.9734/jpri/2021/v33i42a32401
Singh RP, M Narke R, Jadhav PV. Formulation and evaluation of asenapine maleate loaded niosomes for the treatment of schizophrenia. Ind J Pharm Educ [Internet]. 2020;54(2s):s128–39. Available from: http://dx.doi.org/10.5530/ijper.54.2s.69
Parashar AK, Singh G. Synthesis and characterization of ligand-anchored polypropyleneimine dendrimers for the treatment of brain glioma. J Med Pharm Allied Sci. 2021;10(3):2784–9. Available from: http://dx.doi.org/10.22270/jmpas.v10i3.1084
Kotharapu RK, Lankalapalli S. Development and evaluation of Clopidogrel bisulphate multi-unit floating mini-tablets. J Drug Deliv Ther [Internet]. 2019;9(4):173–80. Available from: http://dx.doi.org/10.22270/jddt.v9i4.3169
Abd-Elhakeem E, Teaima MHM, Abdelbary GA, El Mahrouk GM. Bioavailability enhanced clopidogrel -loaded solid SNEDDS: Development and in-vitro/in-vivo characterization. J Drug Deliv Sci Technol [Internet]. 2019;49:603–14. Available from: http://dx.doi.org/10.1016/j.jddst.2018.12.027
Saraogi GK, Bagri R, Singh S, Parashar AK. Formulation Development and Characterization of Surface Modified Pectin Microspheres for Colon Targeting. Bull Env Pharmacol Life Sci. 2023;12(9):16–23.
Parashar AK, Singh G. Synthesis and characterization of temozolomide-loaded theranostic quantum dots for the treatment of brain glioma. J Med Pharm Allied Sci. 2021;10(3):2778–83. Available from: http://dx.doi.org/10.22270/jmpas.v10i3.1073
Agarwal S, Mohamed MS, Raveendran S, Rochani AK, Maekawa T, Kumar DS. Formulation, characterization and evaluation of morusin loaded niosomes for potentiation of anticancer therapy. RSC Adv [Internet]. 2018;8(57):32621–36. Available from: http://dx.doi.org/10.1039/c8ra06362a
Dagariya RK, Jat RK. Method development and validation of clopidogrel drug in the drug substances and dosage form by high performance liquid chromatography. J Drug Deliv Ther [Internet]. 2018;8(4). Available from: http://dx.doi.org/10.22270/jddt.v8i4.1756
El-Laithy HM, Badawi A, Abdelmalak NS, El-Sayyad N. Cubosomes as oral drug delivery systems: A promising approach for enhancing the release of clopidogrel bisulphate in the intestine. Chem Pharm Bull (Tokyo) [Internet]. 2018;66(12):1165–73. Available from: http://dx.doi.org/10.1248/cpb.c18-00615
Parashar AK, Saraogi GK, Sethi VA. Design, formulation, and in vitro evaluation of docetaxel-loaded nanostructured lipid carriers. Int J Med Pharm Health Sci. 2024;1(4):153–62. Available from: http://dx.doi.org/10.62946/ijmphs/1.4.153-162
Venkateswarlu K, Nirosha M, Kumar Reddy BK, Sai Kiran BS. Effect of directly compressible excipient and treated agar on drug release of clopidogrel oral disintegrating tablets. Ther Deliv [Internet]. 2017;8(8):615–24. Available from: http://dx.doi.org/10.4155/tde-2017-0019
Bryniarski KL, Yamamoto E, Takumi H, Xing L, Zanchin T, Sugiyama T, et al. Differences in coronary plaque characteristics between patients with and those without peripheral arterial disease. Coron Artery Dis [Internet]. 2017;28(8):658–63. Available from: http://dx.doi.org/10.1097/MCA.0000000000000531
Reed Chase M, Friedman H, Navaratnam P, Heithoff K, Simpson. Classification tree analysis of the likelihood of clopidogrel treatment in A cohort of patients with symptomatic peripheral artery disease. Value Health [Internet]. 2015;18(3):A33. Available from: http://dx.doi.org/10.1016/j.jval.2015.03.197
Parashar AK, Saraogi GK, Shrivastava V, et al. Development of Angiopep-2 targeted dendrimer-based nanotheranostic system for enhanced temozolomide delivery to glioblastoma multiforme. Bull Natl Res Cent. 2025;49:16. doi:10.1186/s42269-025-01309-3.
Downloads
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.