Skip to content
2000
image of Comparative Study on Enhanced Skin Permeation Efficiency of Phenylephrine via Novel Lipid Vesicles: A Promising Approach in Preventing Chemotherapy-induced Alopecia Management

Abstract

Background

Chemotherapy-induced alopecia (CIA) significantly impacts patients' emotional and psychological well-being and treatment regimen. Phenylephrine, a topical vasoconstrictor, can potentially reduce hair loss by limiting chemotherapy drug delivery to hair follicles. However, effective delivery of Phenylephrine through the skin remains challenging. This study investigates lipid vesicles as delivery vehicles to enhance Phenylephrine's skin permeation and sustained release due to their biocompatibility and encapsulation capabilities.

Objective

This study aimed to formulate and compare different lipid vesicles of Phenylephrine HCl for enhanced permeation through the skin for deep dermal delivery with sustained release of the drug so as to achieve local vasoconstriction.

Methods

Phenylephrine-loaded ethosomes, invasomes, and transfersomes were prepared and characterized for particle size (PS), polydispersity index (PDI), and entrapment efficiency (EE %). These lipid vesicles were incorporated into hydrogels to facilitate sustained drug release to deep dermal layers where they could target local vasculature and cause vasoconstriction. The prepared vesicular gels were evaluated for various permeation parameters.

Results

The entrapment efficiencies of the developed vesicles ranged from 49.51 ± 3.25% to 69.09 ± 2.32%, with vesicle sizes ranging from 162.5 ± 5.21 nm to 321.32 ± 3.75 nm. Statistical analysis revealed significantly higher flux values (Jss, µg/cm2 h) of 0.6251, 0.6314, and 0.4075 for invasomal gel, ethosomal gel, and transfersomal gel, respectively, compared to plain gel (0.1254) ( < 0.005). The enhancement factors were 4.9848, 5.0350, and 3.2496 for invasomal gel, ethosomal gel, and transfersomal gel, respectively, indicating superior permeation abilities of ethosomal and invasomal formulations.

Conclusion

The results demonstrate that ethosomal and invasomal formulations were efficient in delivering the drug to deep dermal layers of skin in a sustained manner. These findings suggest that these Lipidic vesicles would be able to target the local vasoconstrictor to vasculature, causing reduced hair loss by limiting chemotherapy drug delivery to hair follicles and managing chemotherapy-induced alopecia.

Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010336809240815050316
2024-10-18
2024-12-29
Loading full text...

Full text loading...

References

  1. Carelle N. Piotto E. Bellanger A. Germanaud J. Thuillier A. Khayat D. Changing patient perceptions of the side effects of cancer chemotherapy. Cancer 2002 95 1 155 163 10.1002/cncr.10630 12115329
    [Google Scholar]
  2. Balagula Y. Rosen S.T. Lacouture M.E. The emergence of supportive oncodermatology: The study of dermatologic adverse events to cancer therapies. J. Am. Acad. Dermatol. 2011 65 3 624 635 10.1016/j.jaad.2010.06.051 21777992
    [Google Scholar]
  3. Wang J. Lu Z. Au J.L.S. Protection against chemotherapy-induced alopecia. Pharm. Res. 2006 23 11 2505 2514 10.1007/s11095‑006‑9105‑3 16972183
    [Google Scholar]
  4. Bernard M. Brignone M. Adehossi A. Pefoura S. Briquet C. Chouaid C. Tilleul P. Perception of alopecia by patients requiring chemotherapy for non-small-cell lung cancer: A willingness to pay study. Lung Cancer 2011 72 1 114 118 10.1016/j.lungcan.2010.07.004 20701993
    [Google Scholar]
  5. McGarvey E.L. Baum L.D. Pinkerton R.C. Rogers L.M. Psychological sequelae and alopecia among women with cancer. Cancer Pract. 2001 9 6 283 289 10.1111/j.1523‑5394.2001.96007.pp.x 11879330
    [Google Scholar]
  6. Rossi A. Caro G. Fortuna M.C. Pigliacelli F. D’Arino A. Carlesimo M. Prevention and treatment of chemotherapy-induced alopecia. Dermatol. Pract. Concept. 2020 10 3 e2020074 10.5826/dpc.1003a74 32642317
    [Google Scholar]
  7. Santos T.S. Hernandéz Galvis K. Vañó Galván S. Saceda-Corralo D. Post‐chemotherapy alopecia: What the dermatologist needs to know. Int. J. Dermatol. 2021 60 11 1313 1317 10.1111/ijd.15812 34348414
    [Google Scholar]
  8. Freites-Martinez A. Chan D. Sibaud V. Shapiro J. Fabbrocini G. Tosti A. Cho J. Goldfarb S. Modi S. Gajria D. Norton L. Paus R. Cigler T. Lacouture M.E. Assessment of quality of life and treatment outcomes of patients with persistent postchemotherapy alopecia. JAMA Dermatol. 2019 155 6 724 728 10.1001/jamadermatol.2018.5071 30840033
    [Google Scholar]
  9. Kang D. Kim I.R. Choi E.K. Im Y.H. Park Y.H. Ahn J.S. Lee J.E. Nam S.J. Lee H.K. Park J.H. Lee D.Y. Lacouture M.E. Guallar E. Cho J. Permanent chemotherapy-induced alopecia in patients with breast cancer: A 3-year prospective cohort study. Oncologist 2019 24 3 414 420 10.1634/theoncologist.2018‑0184 30120165
    [Google Scholar]
  10. Chan J. Adderley H. Alameddine M. Armstrong A. Arundell D. Fox R. Harries M. Lim J. Salih Z. Tetlow C. Wong H. Thorp N. Permanent hair loss associated with taxane chemotherapy use in breast cancer: A retrospective survey at two tertiary UK cancer centres. Eur. J. Cancer Care (Engl.) 2021 30 3 e13395 10.1111/ecc.13395 33350015
    [Google Scholar]
  11. Trüeb R.M. Chemotherapy-induced hair loss. Skin Therapy Lett. 2010 15 7 5 7 20700552
    [Google Scholar]
  12. Paus R. Haslam I.S. Sharov A.A. Botchkarev V.A. Pathobiology of chemotherapy-induced hair loss. Lancet Oncol. 2013 14 2 e50 e59 10.1016/S1470‑2045(12)70553‑3 23369683
    [Google Scholar]
  13. Breed W.P.M. van den Hurk C.J.G. Peerbooms M. Presentation, impact and prevention of chemotherapy-induced hair loss: Scalp cooling potentials and limitations. Expert. Rev. Dermatol. 2011 6 1 109 125 10.1586/edm.10.76
    [Google Scholar]
  14. Komen M.M.C. Smorenburg C.H. Hurk C.J.G. Nortier J.W.R. Factors influencing the effectiveness of scalp cooling in the prevention of chemotherapy-induced alopecia. Oncologist 2013 18 7 885 891 10.1634/theoncologist.2012‑0332 23650021
    [Google Scholar]
  15. Lemenager M. Lecomte S. Bonneterre M.E. Bessa E. Dauba J. Bonneterre J. Effectiveness of cold cap in the prevention of docetaxel-induced alopecia. Eur. J. Cancer 1997 33 2 297 300 10.1016/S0959‑8049(96)00374‑7 9135504
    [Google Scholar]
  16. Hillen H.F. Breed W.P. Botman C.J. Scalp cooling by cold air for the prevention of chemotherapy-induced alopecia. Neth. J. Med. 1990 37 5-6 231 235 2074916
    [Google Scholar]
  17. Delgado Rodríguez J. Ramos-García V. Infante-Ventura D. Suarez-Herrera J.C. Rueda-Domínguez A. Serrano-Aguilar P. del Mar Trujillo-Martín M. Ethical, legal, organizational and social issues related to the use of scalp cooling for the prevention of chemotherapy‐induced alopecia: A systematic review. Health Expect. 2023 26 2 567 578 10.1111/hex.13679 36585793
    [Google Scholar]
  18. Wang S. Yang T. Shen A. Qiang W. Zhao Z. Zhang F. The scalp cooling therapy for hair loss in breast cancer patients undergoing chemotherapy: A systematic review and meta-analysis. Support. Care Cancer 2021 29 11 6943 6956 10.1007/s00520‑021‑06188‑8 33847828
    [Google Scholar]
  19. Soref C.M. Fahl W.E. A new strategy to prevent chemotherapy and radiotherapy-induced alopecia using topically applied vasoconstrictor. Int. J. Cancer 2015 136 1 195 203 10.1002/ijc.28961 24811525
    [Google Scholar]
  20. Rathman-Josserand M. Genty G. Lecardonnel J. Chabane S. Cousson A. François Michelet J. Bernard B.A. Human hair follicle stem/progenitor cells express hypoxia markers. J. Invest. Dermatol. 2013 133 8 2094 2097 10.1038/jid.2013.113 23474947
    [Google Scholar]
  21. Touitou E. Dayan N. Bergelson L. Godin B. Eliaz M. Ethosomes — Novel vesicular carriers for enhanced delivery: Characterization and skin penetration properties. J. Control. Release 2000 65 3 403 418 10.1016/S0168‑3659(99)00222‑9 10699298
    [Google Scholar]
  22. Elsayed M.M.A. Abdallah O.Y. Naggar V.F. Khalafallah N.M. Lipid vesicles for skin delivery of drugs: Reviewing three decades of research. Int. J. Pharm. 2007 b 332 1-2 1 16 10.1016/j.ijpharm.2006.12.005 17222523
    [Google Scholar]
  23. Dragicevic N. Maibach H.I. Liposomes in transdermal and topical drug delivery. CRC Press 2018
    [Google Scholar]
  24. Moen E.K. Yang S. Anderson J.L. Arndt-Jovin D.J. Overcoming the stratum corneum barrier: A study of permeation enhancers in liposomal delivery systems. J. Control. Release 2019 295 73 84 10.1016/j.jconrel.2019.01.021
    [Google Scholar]
  25. Jøraholmen M.W. Škalko-Basnet N. Acharya G. Basnet P. Liposomal delivery system enhancing dermal and transdermal drug delivery. ACS Omega 2017 2 12 8578 8589 10.1021/acsomega.7b01518
    [Google Scholar]
  26. El Maghraby G.M. Barry B.W. Williams A.C. Liposomes and skin: From drug delivery to model membranes. Eur. J. Pharm. Sci. 2008 34 4-5 203 222 10.1016/j.ejps.2008.05.002 18572392
    [Google Scholar]
  27. Cevc G. Blume G. Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim. Biophys. Acta Biomembr. 1992 1104 1 226 232 10.1016/0005‑2736(92)90154‑E 1550849
    [Google Scholar]
  28. Cevc G. Blume G. New, highly efficient formulation of diclofenac for the topical, transdermal administration in ultradeformable drug carriers, transfersomes. Biochim. Biophys. Acta Biomembr. 2001 1514 2 191 205 10.1016/S0005‑2736(01)00369‑8 11557020
    [Google Scholar]
  29. Maestrelli F. González-Rodríguez M.L. Rabasco A.M. Ghelardini C. Mura P. New “drug-in cyclodextrin-in deformable liposomes” formulations to improve the therapeutic efficacy of local anaesthetics. Int. J. Pharm. 2010 395 1-2 222 231 10.1016/j.ijpharm.2010.05.046 20594944
    [Google Scholar]
  30. Dayan N. Touitou E. Carriers for skin delivery of trihexyphenidyl HCl: Ethosomes vs. liposomes. Biomaterials 2000 21 18 1879 1885 10.1016/S0142‑9612(00)00063‑6 10919691
    [Google Scholar]
  31. Godin B. Touitou E. Ethosomes: New prospects in transdermal delivery. Crit. Rev. Ther. Drug Carrier Syst. 2003 20 1 63 102 10.1615/CritRevTherDrugCarrierSyst.v20.i1.20 12911264
    [Google Scholar]
  32. Kamran M. Ahad A. Aqil M. Imam S.S. Sultana Y. Ali A. Design, formulation and optimization of novel soft nano-carriers for transdermal olmesartan medoxomil delivery: In vitro characterization and in vivo pharmacokinetic assessment. Int. J. Pharm. 2016 505 1-2 147 158 10.1016/j.ijpharm.2016.03.030 27005906
    [Google Scholar]
  33. Ahmed O.A.A. Badr-Eldin S.M. Development of an optimized avanafil-loaded invasomal transdermal film: Ex vivo skin permeation and in vivo evaluation. Int. J. Pharm. 2019 570 118657 10.1016/j.ijpharm.2019.118657 31491483
    [Google Scholar]
  34. El-Nabarawi M.A. Shamma R.N. Farouk F. Nasralla S.M. Dapsone-loaded invasomes as a potential treatment of acne: Preparation, characterization, and in vivo skin deposition assay. AAPS PharmSciTech 2018 19 5 2174 2184 10.1208/s12249‑018‑1025‑0 29725903
    [Google Scholar]
  35. Lin H. Yu C. Lei W. Zhou X. Development of tacrolimus-loaded transfersomes for deeper skin penetration enhancement and therapeutic effect improvement in vivo. Asian. Asian. Jour. Pharm. Sci. 2013 336 345 10.1016/j.ajps.2013.09.005.
    [Google Scholar]
  36. Abdelbary A.A. AbouGhaly M.H.H. Design and optimization of topical methotrexate loaded niosomes for enhanced management of psoriasis: Application of Box–Behnken design, in-vitro evaluation and in-vivo skin deposition study. Int. J. Pharm. 2015 485 1-2 235 243 10.1016/j.ijpharm.2015.03.020 25773359
    [Google Scholar]
  37. Zweers M.L.T. Grijpma D.W. Engbers G.H.M. Feijen J. The preparation of monodisperse biodegradable polyester nanoparticles with a controlled size. J. Biomed. Mater. Res. B Appl. Biomater. 2003 66B 2 559 566 10.1002/jbm.b.10046 12861608
    [Google Scholar]
  38. Ichino T. Yotsuyanagi T. Mizuno I. Akamo Y. Yamamoto T. Saito T. Kurahashi S. Tanimoto N. Yura J. Antitumor effect of liposome-entrapped adriamycin administered via the portal vein. Jpn. J. Cancer Res. 1990 81 10 1052 1056 10.1111/j.1349‑7006.1990.tb03345.x 2121678
    [Google Scholar]
  39. Patel N.A. Patel N.J. Patel R.P. Formulation and evaluation of curcumin gel for topical application. Pharm. Dev. Technol. 2009 14 1 83 92 10.1080/10837450802409438 18821270
    [Google Scholar]
  40. Pavelić Ž. Škalko-Basnet N. Schubert R. Liposomal gels for vaginal drug delivery. Int. J. Pharm. 2001 219 1-2 139 149 10.1016/S0378‑5173(01)00637‑8 11337174
    [Google Scholar]
  41. Kaur L.P. Garg R. Gupta G.D. Development and evaluation of topical gel of minoxidil from different polymer bases in application of alopecia. Int. J. Pharm. Pharm. Sci. 2010 2 43 47
    [Google Scholar]
  42. Bachhav YG. Patravale VB. Microemulsion based vaginal gel of fluconazole: Formulation, in vitro and in vivo evaluation. Int J Pharm. 2009 365 1-2 175 9 10.1016/j.ijpharm.2008.08.021.
    [Google Scholar]
  43. Chaudhary H. Rohilla A. Rathee P. Kumar V. Optimization and formulation design of carbopol loaded Piroxicam gel using novel penetration enhancers. Int. J. Biol. Macromol. 2013 55 246 253 10.1016/j.ijbiomac.2013.01.015 23376559
    [Google Scholar]
  44. Verma H. Pal D.P. Joshi D. Formulation, development and evaluation of invasomes loaded gel for fungal treatment. Sch. Acad. J. Pharm. 2022 11 7 105 108 10.36347/sajp.2022.v11i07.001
    [Google Scholar]
  45. Kumar B. Sahoo P.K. Manchanda S. Formulation, characterization and ex vivo study of curcumin nano-invasomal gel for enhanced transdermal delivery. OpenNano 2022 7 100058 10.1016/j.onano.2022.100058
    [Google Scholar]
  46. Ramteke S. Barupal A.K. Gupta V. Preparation and characterization of ethosomes for topical delivery of aceclofenac. Indian J. Pharm. Sci. 2010 72 5 582 586 10.4103/0250‑474X.78524 21694989
    [Google Scholar]
  47. Maurya Sheo Datta. Prajapati Sunil Kumar. Gupta Anish Kumar. Saxena Gyanendra Kumar. Dhakar Ram Chand. Formulation development and evaluation of ethosome of stavudine. Indian. J. Pharm. Educ. Res. 2010 44 1 102 108 10.2139/ssrn.3774625. 2010
    [Google Scholar]
  48. Paolino D. Lucania G. Mardente D. Alhaique F. Fresta M. Ethosomes for skin delivery of ammonium glycyrrhizinate: In vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers. J. Control. Release 2005 106 1-2 99 110 10.1016/j.jconrel.2005.04.007 15935505
    [Google Scholar]
  49. Nurmahliati H. Widodo F. Puspita O. Effect of soy lecithin and sodium cholate concentration on characterization pterostilbene transfersomes. Indones. J. Pharm 2020 5 2 109 115 10.21776/ub.pji.2020.005.02.7
    [Google Scholar]
  50. Zubaydah W. O. S. Andriani R. Suryani S. Indalifiani .A Jannah S.R.N. Hidayati D. Optimization of soya phosphatidylcholine and tween 80 as a preparation of diclofenac sodium transfersome vesicles using design-expert. Galenika J. Pharm. 2023 9 1 84 98 10.22487/j24428744.2023.v9.i1.16085
    [Google Scholar]
  51. Jadupati M. Kumar N.A. Transferosome: An opportunistic carrier for transdermal drug delivery system. Int. Res. J. Pharm. 2012 3 35 38
    [Google Scholar]
  52. Dubey V. Mishra D. Dutta T. Nahar M. Saraf D.K. Jain N.K. Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes. J. Control. Release 2007 123 2 148 154 10.1016/j.jconrel.2007.08.005 17884226
    [Google Scholar]
  53. Kim B.P.G. Mendes L.P. Lu M.J.T.Y. Optimizing vesicle size for effective skin penetration and drug delivery. J. Control. Release 2018 285 13 23 10.1016/j.jconrel.2018.06.029
    [Google Scholar]
  54. Tariq M.A.S. Singh A.G. Smith A.H. Lopez C.M. Nanoparticle size and skin penetration: The role of vesicle size in dermal drug delivery. Eur. J. Pharm. Biopharm. 2018 130 132 145 10.1016/j.ejpb.2018.07.012
    [Google Scholar]
  55. Park J.H. Jang L.B. Lee M.K. The role of vesicle size in dermal delivery of therapeutics: comparative analysis of different lipid vesicles. J. Control. Release 2019 300 118 130 10.1016/j.jconrel.2019.01.002
    [Google Scholar]
  56. Saryanti D. Zulfa I.N. Optimization carbopol and glycerol as basis of hand gel antiseptics extract ethanol ceremai leaf (Phyllantus acidus (L.) Skeels) with simplex lattice design. JPSCR 2017 2 1 35 43 10.20961/jpscr.v2i01.5238
    [Google Scholar]
  57. Rowe R.C. Sheskey P.J. Quinn M.E. Handbook of Pharmaceutical Excipients. Pharmaceutical Press and American Pharmacists Association 2009
    [Google Scholar]
  58. Kurniawansyah I.S. Rusdiana T. Sopyan I. Desy Arya I.F. Wahab H.A. Nurzanah D. Comparative study of in situ gel formulation based on the physico-chemical aspect: Systematic review. Gels 2023 9 8 645 10.3390/gels9080645 37623100
    [Google Scholar]
  59. Shinde U. Pokharkar S. Modani S. Design and evaluation of microemulsion gel system of nadifloxacin. Indian J. Pharm. Sci. 2012 74 3 237 247 10.4103/0250‑474X.106066 23439454
    [Google Scholar]
  60. Lohani A. Formulation, development and evaluation of ciprofloxacin hydrochloride soft gel for oral administration. 2011
    [Google Scholar]
  61. Carvalho F.C. Barbi M.S. Sarmento V.H.V. Chiavacci L.A. Netto F.M. Gremião M.P.D. Surfactant systems for nasal zidovudine delivery: structural, rheological and mucoadhesive properties. J. Pharm. Pharmacol. 2010 62 4 430 439 10.1211/jpp.62.04.0004 20604831
    [Google Scholar]
  62. Lei W. Yu C. Lin H. Zhou X. Development of tacrolimus-loaded transfersomes for deeper skin penetration enhancement and therapeutic effect improvement in vivo. Asian. Jour. Pharm. Sci 2013 8 6 336 345 10.1016/j.ajps.2013.09.005
    [Google Scholar]
  63. Zhang J.P. Wei Y.H. Zhou Y. Li Y.Q. Wu X.A. Ethosomes, binary ethosomes and transfersomes of terbinafine hydrochloride: A comparative study. Arch. Pharm. Res. 2012 35 1 109 117 10.1007/s12272‑012‑0112‑0 22297749
    [Google Scholar]
  64. Elsayed M.M. Abdallah O.Y. Naggar V.F. Khalafallah N.M. Deformable liposomes and ethosomes as carriers for skin delivery of ketotifen. Pharmazie 2007 62 2 133 137 17341034
    [Google Scholar]
  65. Ahad A. Aqil M. Kohli K. Sultana Y. Mujeeb M. Ali A. Role of novel terpenes in transcutaneous permeation of valsartan: effectiveness and mechanism of action. Drug Dev. Ind. Pharm. 2011 37 5 583 596 10.3109/03639045.2010.532219 21469947
    [Google Scholar]
  66. Lakshmi P.K. Kalpana B. Prasanthi D. Invasomes-novel vesicular carriers for enhanced skin permeation. Sys Rev Pharm 2013 4 1 26 30 10.4103/0975‑8453.135837
    [Google Scholar]
/content/journals/cpb/10.2174/0113892010336809240815050316
Loading
/content/journals/cpb/10.2174/0113892010336809240815050316
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test