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2000
Volume 13, Issue 3
  • ISSN: 2211-7385
  • E-ISSN: 2211-7393

Abstract

Objective

The study aimed to address the limitations of oral delivery and enhance the bioavailability of Cilnidipine (often prescribed as antihypertensive drug) (CND) through the development of transdermal patches containing ultra-deformable transferosomes.

Methods

CND, known for its low oral bioavailability and adverse effects, was encapsulated in transferosomes using a thin film hydration method. Seventeen formulations were made (using Box Behnken Design), varying Soya lecithin, Tween-80, and rotary evaporator’s speed, and evaluated for vesicle size, polydispersity index (PDI), and entrapment efficiency (EE %). The better formulation was selected based on these parameters and incorporated into transdermal patches. Physicochemical properties, and permeation, and skin irritancy studies were conducted on the patches. Pharmacokinetic studies were conducted using male Wistar albino rats.

Results

The study found that the developed transferosomal formulations had vesicle sizes between 185 nm and 401 nm, entrapment efficiency (EE%) between 63% and 92%, and zeta potential ranging from -52 mV to -20 mV. Both and permeation studies showed that transferosomal formulations provided significantly better drug permeation than plain Cilnidipine patches, with increased permeation linked to higher PEG-400 concentrations. The transferosomal patches did not cause skin irritation. The optimized formulation exhibited a higher % drug release (85.7±1.5%). In pharmacokinetic studies using male Wistar albino rats, the transferosomal patch CTP-17 demonstrated a higher maximum concentration (Cmax) of 1565.068 mcg/ml and a greater area under the curve (AUC) of 13225.352 μg h/ml compared to oral administration.

Conclusion

The study concludes that the transferosomal patches of CND offer a promising approach for effective transdermal delivery, potentially improving hypertension management for prolonged periods in a controlled manner.

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2024-11-04
2025-10-19

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References

  1. ManciaG. KreutzR. BrunströmM. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension.J. Hypertens.202341121874207110.1097/HJH.0000000000003480 37345492
     [Google Scholar]
  2. AkombaetwaN. IlangalaA.B. ThomL. MemvangaP.B. WitikaB.A. BuyaA.B. Current advances in lipid nanosystems intended for topical and transdermal drug delivery applications.Pharmaceutics202315265610.3390/pharmaceutics15020656 36839978
     [Google Scholar]
  3. DengP. Athary AbdulhaleemM.F. MasoudR.E. AlamoudiW.M. ZakariaM.Y. Employment of PEGylated ultra-deformable transferosomes for transdermal delivery of tapentadol with boosted bioavailability and analgesic activity in post-surgical pain.Int. J. Pharm.202262812227410.1016/j.ijpharm.2022.122274 36228884
     [Google Scholar]
  4. KabirM.A. SufianM.M. HossainM.M. SiddiquiM.M.A. KadirA.M. SultanaI. Comparison between the efficacies of amlodipine and cilnidipine in treating hypertensive patients.Med Res Chron2023103122127
     [Google Scholar]
  5. AlyahyaE.M. AlwabsiK. AljohaniA.E. Preparation and optimization of itraconazole transferosomes-loaded HPMC hydrogel for enhancing its antifungal activity: 2^ 3 full factorial design.Polymers 202315499510.3390/polym15040995 36850278
     [Google Scholar]
  6. Padma PrashanthiniV. SivaramanS. KathirveluP. Transferosomal gel for transdermal delivery of insulin: Formulation development and ex vivo permeation study.Intell Pharm20231421221610.1016/j.ipha.2023.07.001
     [Google Scholar]
  7. KharwadeR. AliN. GanganeP. DOE-assisted formulation optimization and characterization of tioconazole-loaded transferosomal hydrogel for the effective treatment of atopic dermatitis: in vitro and in vivo evaluation.Gels20239430310.3390/gels9040303 37102915
     [Google Scholar]
  8. MazharD. HaqN.U. ZeeshanM. Preparation, characterization, and pharmacokinetic assessment of metformin HCl loaded transfersomes co-equipped with permeation enhancer to improve drug bioavailability via transdermal route.J. Drug Deliv. Sci. Technol.20238410444810.1016/j.jddst.2023.104448
     [Google Scholar]
  9. FitryaF FithriNA AhmadiA WijayaDP PitalokaAD Formulation and characterization of transfersome gel from Parkia speciosa extract using carbopol 940 and polyvinyl alcohol Medicinal Plants - International Journal of Phytomedicines and Related Industries 202214349950610.5958/0975‑6892.2022.00055.7
     [Google Scholar]
  10. WaheedA. AqilM. AhadA. Improved bioavailability of raloxifene hydrochloride using limonene containing transdermal nano-sized vesicles.J. Drug Deliv. Sci. Technol.20195246847610.1016/j.jddst.2019.05.019
     [Google Scholar]
  11. JainS. JainP. UmamaheshwariR.B. JainN.K. Transfersomes--a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation.Drug Dev. Ind. Pharm.20032991013102610.1081/DDC‑120025458 14606665
     [Google Scholar]
  12. WuP.S. LiY.S. KuoY.C. TsaiS.J.J. LinC.C. Preparation and evaluation of novel transfersomes combined with the natural antioxidant resveratrol.Molecules201924360010.3390/molecules24030600 30743989
     [Google Scholar]
  13. DuangjitS. OpanasopitP. RojanarataT. NgawhirunpatT. Evaluation of meloxicam-loaded cationic transfersomes as transdermal drug delivery carriers.AAPS PharmSciTech201314113314010.1208/s12249‑012‑9904‑2 23242556
     [Google Scholar]
  14. SultanaS.S. Krishna SailajaA. Formulation and evaluation of diclofenac sodium transferosomes using different surfactants by thin film hydration method.Pharm. Lett.20157114353
     [Google Scholar]
  15. ShreyaA.B. ManaguliR.S. MenonJ. Nano-transfersomal formulations for transdermal delivery of asenapine maleate: in vitro and in vivo performance evaluations.J. Liposome Res.201626322123210.3109/08982104.2015.1098659 26621370
     [Google Scholar]
  16. Abd El-AlimS.H. KassemA.A. BashaM. SalamaA. Comparative study of liposomes, ethosomes and transfersomes as carriers for enhancing the transdermal delivery of diflunisal: In vitro and in vivo evaluation.Int. J. Pharm.201956329330310.1016/j.ijpharm.2019.04.001 30951860
     [Google Scholar]
  17. ShammaR.N. ElsayedI. Transfersomal lyophilized gel of buspirone HCl: formulation, evaluation and statistical optimization.J. Liposome Res.201323324425410.3109/08982104.2013.801489 23713516
     [Google Scholar]
  18. ZhengW. FangX. WangL. ZhangY. Preparation and quality assessment of itraconazole transfersomes.Int. J. Pharm.20124361-229129810.1016/j.ijpharm.2012.07.003 22796030
     [Google Scholar]
  19. ThakurN. JainP. JainV. Formulation development and evaluation of transferosomal gel.J. Drug Deliv. Ther.20188516817710.22270/jddt.v8i5.1826
     [Google Scholar]
  20. MahmoodS. ChatterjeeB. MandalU.K. Pharmacokinetic evaluation of the synergistic effect of raloxifene loaded transfersomes for transdermal delivery.J. Drug Deliv. Sci. Technol.20216310254510.1016/j.jddst.2021.102545
     [Google Scholar]
  21. BensonH.A.E. Transfersomes for transdermal drug delivery.Expert Opin. Drug Deliv.20063672773710.1517/17425247.3.6.727 17076595
     [Google Scholar]
  22. JoshiA. KaurJ. KulkarniR. ChaudhariR. In-vitro and Ex-vivo evaluation of Raloxifene hydrochloride delivery using nano-transfersome based formulations.J. Drug Deliv. Sci. Technol.20184515115810.1016/j.jddst.2018.02.006
     [Google Scholar]
  23. ChenM. ShamimM.A. ShahidA. Topical delivery of carvedilol loaded nano-transfersomes for skin cancer chemoprevention.Pharmaceutics20201212115110.3390/pharmaceutics12121151 33260886
     [Google Scholar]
  24. GuptaA. AggarwalG. SinglaS. AroraR. Transfersomes: a novel vesicular carrier for enhanced transdermal delivery of sertraline: development, characterization, and performance evaluation.Sci. Pharm.20128041061108010.3797/scipharm.1208‑02 23264950
     [Google Scholar]
  25. SiddaramaiahR.N. GowdaD.V. SomshekarC.N. Formulation and evaluation of biopolymer based transdermal drug delivery.Int. J. Pharma Sci.20102142147
     [Google Scholar]
  26. PraveenM. Someswara RaoB. KulkarniS.V. Chethan Surpur, Basavaraj. Formulation and Evaluation of Tizanidine Hydrochloride Transdermal Patches.Int J Drug Pharm Res201122298313
     [Google Scholar]
  27. GuptaR. KumarA. Transfersomes: the ultra-deformable carrier system for non-invasive delivery of drug.Curr. Drug Deliv.202118440842010.2174/1567201817666200804105416 32753015
     [Google Scholar]
  28. AhadA. Al-SalehA.A. Al-MohizeaA.M. Formulation and characterization of Phospholipon 90 G and tween 80 based transfersomes for transdermal delivery of eprosartan mesylate.Pharm. Dev. Technol.201823878779310.1080/10837450.2017.1330345 28504046
     [Google Scholar]
  29. GeinozS. MitragotriS. LangerR. FahrA. GuyR.H. Mechanisms of solute transport across the stratum corneum: Effect of lipid concentration.Pharm. Res.2004214753759
     [Google Scholar]
  30. LyS.Y. LongoW.E. Intercellular pathways and transport mechanisms in human skin.Adv. Drug Deliv. Rev.2004565665679
     [Google Scholar]
  31. GuptaS. TrivediN. Enhancing transdermal drug delivery using nanocarriers: Formulation strategies and applications.Ther. Deliv.201678569582
     [Google Scholar]
  32. CevcG. VierlU. Transdermal drug delivery using ultradeformable vesicles: Mechanisms and applications.Biochim. Biophys. Acta2010179813848 19660431
     [Google Scholar]
  33. SchätzleinA. CevcG. Non-uniform distribution of drug molecules in the stratum corneum: A critical factor for transdermal drug delivery.J. Control. Release1998561-3257264 9685892
     [Google Scholar]
  34. MitragotriS. Modeling skin permeability for transdermal drug delivery.Adv. Drug Deliv. Rev.200354Suppl. 137
     [Google Scholar]
  35. JohnsonM.E. BlankschteinD. LangerR. Permeation of drugs through human skin: Mechanistic studies using fluorescent tracers.J. Pharm. Sci.199786101162117010.1021/js960198e 9344175
     [Google Scholar]
  36. MorieartyP.L. ThorntonS.L. BeckerR.E. Enhancing transdermal drug delivery using microelectrodes.Methods Find. Exp. Clin. Pharmacol.1993156407413 8231460
     [Google Scholar]
  37. SiegelS.J. O’NeillC. DubeL. KaldewayP. MorrisR. JacksonD. Efficacy of microneedle-assisted transdermal drug delivery.Headache2007475753763
     [Google Scholar]
  38. BlankschteinD. PolatB.E. HartD. LangerR. Combining physical and chemical approaches for enhanced transdermal drug delivery.J. Control. Release20111523330338 21238514
     [Google Scholar]
  39. BangaA.K. LiG.H. BadkarA. KalluriH. Transdermal delivery of therapeutic agents using microneedles and electroporation.J. Pharm. Sci.201099419311939 19894263
     [Google Scholar]
  40. TouitouE. DayanN. BergelsonL. GodinB. EliazM. Ethosomes for enhanced transdermal drug delivery.J. Control. Release200065340341810.1016/S0168‑3659(99)00222‑9 10699298
     [Google Scholar]
  41. PrausnitzM.R. Microneedles for transdermal drug delivery.Adv. Drug Deliv. Rev.200456558158710.1016/j.addr.2003.10.023 15019747
     [Google Scholar]
  42. LankeS. KolliC. StromJ. BangaA. Enhanced transdermal delivery of low molecular weight heparin by barrier perturbation.Int. J. Pharm.20093651-2263310.1016/j.ijpharm.2008.08.028 18801420
     [Google Scholar]
  43. DonnellyR.F. SinghT.R.R. GarlandM.J. MigalskaK. MajithiyaR. McCruddenC.M. Hydrogel-forming microneedle arrays for enhanced transdermal drug delivery.Adv. Drug Deliv. Rev.201463500508
     [Google Scholar]
  44. BlankschteinD. LangerR. Ultrasound-enhanced transdermal drug delivery: Mechanistic studies.Ther. Deliv.20145784385710.4155/tde.14.32 25287389
     [Google Scholar]
  45. JohnsonM.E. BlankschteinD. LangerR. Role of stratum corneum lipid heterogeneity in transdermal drug delivery.Biochim. Biophys. Acta199713282311320
     [Google Scholar]
  46. PrausnitzM.R. LangerR. Transdermal drug delivery.Nat. Biotechnol.200826111261126810.1038/nbt.1504 18997767
     [Google Scholar]
  47. CevcG. GebauerD. Enhanced transdermal delivery using deformable vesicles.Biochim. Biophys. Acta19981368220121510.1016/S0005‑2736(97)00177‑6 9459598
     [Google Scholar]
  48. KumarR. KhatakS. ChiaY.H. SinnathambiA. VethamuthuS. Enhanced transdermal delivery of ibuprofen via transfersomes: formulation, characterization, and in vivo evaluation.J. Liposome Res.2022324300310
     [Google Scholar]
  49. SachanR. BajpaiM. Transferosomes: a promising tool for transdermal delivery of protein and peptides.Ther. Deliv.201344497511
     [Google Scholar]
  50. CevcG. BlumeG. Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force.Biochim. Biophys. Acta200316142115129 12896808
     [Google Scholar]
  51. YangS.C. ChoiM.K. ShinS.C. ChoJ.W. ShinY. LeeC.W. Enhanced skin permeation of human growth hormone using transfersome as a carrier system.Int. J. Pharm.20022331-289101 12433437
     [Google Scholar]
  52. GhanbarzadehS. AramiS. Enhanced transdermal delivery of diclofenac sodium via conventional liposomes, ethosomes, and transfersomes.BioMed Res. Int.201320131710.1155/2013/616810 23936825
     [Google Scholar]
  53. CevcG. GebauerD. Hydrocortisone and dexamethasone in very deformable drug carriers have increased biological potency, prolonged effect, and reduced therapeutic dosage.Biochim. Biophys. Acta19981368220121510.1016/S0005‑2736(97)00177‑6 9459598
     [Google Scholar]
  54. PaulA. Therapeutic applications of transferosomes.Drug Deliv Technol199824456463
     [Google Scholar]
  55. MishraM. SinghD. DubeyP. BhattacharyaS. Formulation and characterization of propranolol hydrochloride loaded transferosomes: a vesicular system for transdermal delivery.J. Drug Deliv. Sci. Technol.201949305312
     [Google Scholar]
  56. MauryaS.D. AgarwalS. TilakV.K. DhakarR.C. SinghA. MauryaG. Enhanced transdermal delivery of indinavir sulfate via transferosomes.Int J Compr Pharm20101117
     [Google Scholar]
  57. CevcG. Transfersomes, liposomes and other lipid suspensions on the skin: permeation enhancement, vesicle penetration, and transdermal drug delivery.Crit. Rev. Ther. Drug Carrier Syst.1996133-425738810.1615/CritRevTherDrugCarrierSyst.v13.i3‑4.30 9016383
     [Google Scholar]
  58. KwonM. ChoiH.E. KimK.S. Recent advances in transdermal drug delivery systems: A review.Biomater. Res.2021251115 33451366
     [Google Scholar]
  59. CaudillR. MoonS. LaiZ. MbahC. Recent advances and future prospective of topical and transdermal delivery systems.Front. Pharmacol.2022131151
     [Google Scholar]
  60. TouitouE. DayanN. BergelsonL. GodinB. EliazM. Ethosomes—new prospects in transdermal delivery.J. Control. Release200065340341810.1016/S0168‑3659(99)00222‑9 10699298
     [Google Scholar]
  61. CammaranoA. Dello IaconoS. MeglioC. NicolaisL. Pharmaceutics. Advances in transdermal drug delivery systems: A bibliometric and patent analysis.Pharmaceutics20231512276210.3390/pharmaceutics15122762 38140102
     [Google Scholar]
  62. MdandaS. UbanakoP. KondiahP.P.D. KumarP. ChoonaraY.E. Polymers. Recent advances in microneedle platforms for transdermal drug delivery technologies.Polymers (Basel)20211315240510.3390/polym13152405 34372008
     [Google Scholar]
  63. MedinaJ. SmithA. KimK. Advances in transdermal drug delivery.Biotechnol. Adv.2019373666679
     [Google Scholar]
  64. GuptaA. SachanR. Role of nanotechnology in transdermal drug delivery.Ther. Deliv.201344497511
     [Google Scholar]
  65. GuptaS. TrivediN. Nanocarriers for transdermal drug delivery: Recent advances and future trends.Ther. Deliv.201678569582
     [Google Scholar]
  66. CevcG. VierlU. Novel vesicular carriers for transdermal delivery: Liposomes and transfersomes.Biochim. Biophys. Acta2010179813848 19660431
     [Google Scholar]
  67. SiegelS.J. O’NeillC. DubeL. KaldewayP. MorrisR. JacksonD. Microneedle patches for vaccine delivery.Headache2007475753763
     [Google Scholar]
  68. BlankschteinD. LangerR. Enhancing transdermal drug delivery: Combining physical and chemical approaches.J. Control. Release20111523330338 21238514
     [Google Scholar]
  69. DonnellyR.F. SinghT.R.R. GarlandM.J. MigalskaK. MajithiyaR. McCruddenC.M. Hydrogel-forming microneedle arrays: Versatile devices for enhanced transdermal drug delivery.Adv. Drug Deliv. Rev.201463500508
     [Google Scholar]
  70. BangaA.K. LiG.H. BadkarA. KalluriH. Microneedles and electroporation for transdermal drug delivery.J. Pharm. Sci.201099419311939 19894263
     [Google Scholar]
  71. CevcG. GebauerD. Deformable vesicles for enhanced transdermal delivery: Innovations and applications.Biochim. Biophys. Acta19981368220121510.1016/S0005‑2736(97)00177‑6 9459598
     [Google Scholar]
/content/journals/pnt/10.2174/0122117385334963241015164501
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Enhanced Transdermal Delivery of Cilnidpine Via Ultradeformable Vesicle Loaded Patch: Statistical Optimization, Characterization and Pharmacokinetic Assessment
Pharm. Nanotechnol. 13, 564 (2025); https://doi.org/10.2174/0122117385334963241015164501
/content/journals/pnt/10.2174/0122117385334963241015164501
/content/journals/pnt/10.2174/0122117385334963241015164501
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  • Article Type:     Research Article
Keyword(s): antihypertensive drug; Cilnidipine; drug permeation; hypertension management; transdermal patches; transferosomes

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