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. 2007 Dec 14;8(4):213. doi: 10.1208/pt0804107

Enhanced transdermal delivery of salbutamol sulfate via ethosomes

Ehab R Bendas 1, Mina I Tadros 1,✉
PMCID: PMC2750693  PMID: 18181528

Abstract

The main objective of the present work was to compare the transdermal delivery of salbutamol sulfate (SS), a hydrophilic drug used as a bronchodilator, from ethosomes and classic liposomes containing different cholesterol and dicetylphosphate concentrations. All the systems were characterized for shape, particle size, and entrapment efficiency percentage, by image analysis optical microscopy or transmission electron microscopy, laser diffraction, and ultracentrifugation, respectively. In vitro drug permeation via a synthetic semipermeable membrane or skin from newborn mice was studied in Franz diffusion cells. The selected systems were incorporated into Pluronic F 127 gels and evaluated for both drug permeation and mice skin deposition. In all systems, the presence of spherical-shaped vesicles was predominant. The vesicle size was significantly decreased (P<.05) by decreasing cholesterol concentration and increasing dicetylphosphate and ethanol concentrations. The entrapment efficiency percentage was significantly increased (P<.05) by increasing cholesterol, dicetylphosphate, and ethanol concentrations. In vitro permeation studies of the prepared gels containing the selected vesicles showed that ethosomal systems were much more efficient at delivering SS into mice skin (in terms of quantity and depth) than were liposomes or aqueous or hydroalcoholic solutions.

Keywords: Transdermal, salbutamol sulfate, liposomes, ethosomes

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References

  • 1.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;65:403–418. doi: 10.1016/S0168-3659(99)00222-9. [DOI] [PubMed] [Google Scholar]
  • 2.Kirjavainen M, Urtti A, Jaaskelainen I, et al. Interaction of liposomes with human skin in vitro—the influence of lipid composition and structure. Biochim Biophys Acta. 1996;1304:179–189. doi: 10.1016/s0005-2760(96)00126-9. [DOI] [PubMed] [Google Scholar]
  • 3.El Sayed MA, Abdallah OY, Naggar VF, Khalafallah NM. Deformable liposomes and ethosomes: mechanism of enhanced skin delivery. Int J Pharm. 2006;322:60–66. doi: 10.1016/j.ijpharm.2006.05.027. [DOI] [PubMed] [Google Scholar]
  • 4.Cevc G, Blume G. Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim Biophys Acta. 1992;1104:226–232. doi: 10.1016/0005-2736(92)90154-E. [DOI] [PubMed] [Google Scholar]
  • 5.Honeywell-Nguyen PL, Bouwstra JA. Vesicles as a tool for transdermal and dermal delivery. Drug Discov Today. 2005;2:67–74. doi: 10.1016/j.ddtec.2005.05.003. [DOI] [PubMed] [Google Scholar]
  • 6.Benson HA. Transfersomes for transdermal drug delivery. Expert Opin Drug Deliv. 2006;3:727–737. doi: 10.1517/17425247.3.6.727. [DOI] [PubMed] [Google Scholar]
  • 7.Oh YK, Kim MY, Shin JY, et al. Skin permeation of retinol in Tween 20-based deformable liposomes: in-vitro evaluation in human skin and keratinocyte models. J Pharm Pharmacol. 2006;58:161–166. doi: 10.1211/jpp.58.2.0002. [DOI] [PubMed] [Google Scholar]
  • 8.Trotta M, Peira E, Carlotti ME, Gallarate M. Deformable liposomes for dermal administration of methotrexate. Int J Pharm. 2004;270:119–125. doi: 10.1016/j.ijpharm.2003.10.006. [DOI] [PubMed] [Google Scholar]
  • 9.Cevc G, Blume G. Hydrocortisone and dexamethasone in very deformable drug carriers have increased biological potency, prolonged effect, and reduced therapeutic dosage. Biochim Biophys Acta. 2004;1663:61–73. doi: 10.1016/j.bbamem.2004.01.006. [DOI] [PubMed] [Google Scholar]
  • 10.Ainbinder D, Touitou E. Testosterone ethosomes for enhanced transdermal delivery. Drug Deliv. 2005;12:297–303. doi: 10.1080/10717540500176910. [DOI] [PubMed] [Google Scholar]
  • 11.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;106:99–110. doi: 10.1016/j.jconrel.2005.04.007. [DOI] [PubMed] [Google Scholar]
  • 12.Magnusson BM, Runn P, Karlsson K, Koskinen L. Terpenes and ethanol enhance the transdermal permeation of the tripeptide thyrotropin releasing hormone in human epidermis. Int J Pharm. 1997;157:113–121. doi: 10.1016/S0378-5173(97)00235-4. [DOI] [Google Scholar]
  • 13.Lopez-Pinto JM, Gonzalez-Rodriguez ML, Rabasco AM. Effect of cholesterol and ethanol on dermal delivery from DPPC liposomes. Int J Pharm. 2005;298:1–12. doi: 10.1016/j.ijpharm.2005.02.021. [DOI] [PubMed] [Google Scholar]
  • 14.Godin B, Touitou E. Erythromycin ethosomal systems: physicochemical characterization and enhanced antibacterial activity. Curr Drug Deliv. 2005;2:269–275. doi: 10.2174/1567201054367931. [DOI] [PubMed] [Google Scholar]
  • 15.Godin B, Touitou E. Mechanism of bacitracin permeation enhancement through the skin and cellular membranes from an ethosomal carrier. J Control Release. 2004;94:365–379. doi: 10.1016/j.jconrel.2003.10.014. [DOI] [PubMed] [Google Scholar]
  • 16.Kelly HW, Murphy S. Beta-adrenergic agonists for acute, severe asthma. Ann Pharmacother. 1992;26:81–91. doi: 10.1177/106002809202600115. [DOI] [PubMed] [Google Scholar]
  • 17.Hochhaus G, Mollmann H. Pharmacokinetic/pharmacodynamic characteristics of the beta-2-agonists terbutaline, salbutamol and fenoterol. Int J Clin Pharmacol Ther Toxicol. 1992;30:342–362. [PubMed] [Google Scholar]
  • 18.Sweetman SC. Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press; 2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Holimon TD, Chafin CC, Self TH. Nocturnal asthma uncontrolled by inhaled corticosteroids: theophylline or long-acting beta2 agonists? Drugs. 2001;61:391–418. doi: 10.2165/00003495-200161030-00007. [DOI] [PubMed] [Google Scholar]
  • 20.Murthy SN, Hiremath SR. Clinical pharmacokinetic and pharmacodynamic evaluation of transdermal drug delivery systems of salbutamol sulfate. Int J Pharm. 2004;287:47–53. doi: 10.1016/j.ijpharm.2004.08.018. [DOI] [PubMed] [Google Scholar]
  • 21.Liang W, Levchenko TS, Torchilin VP. Encapsulation of ATP into liposomes by different methods: optimization of the procedure. J Microencapsul. 2004;21:251–261. doi: 10.1080/02652040410001673900. [DOI] [PubMed] [Google Scholar]
  • 22.Sentjurc M, Vrhovnik K, Kristl J. Liposomes as a topical delivery system: the role of size on transport studied by the EPR imaging method. J Control Rel. 1999;59:87–97. doi: 10.1016/S0168-3659(98)00181-3. [DOI] [PubMed] [Google Scholar]
  • 23.Kanikkannan N, Singh J, Ramarao P. In vitro transdermal iontophoretic transport of timolol maleate: effect of age and species. J Control Rel. 2001;71:99–105. doi: 10.1016/S0168-3659(01)00208-5. [DOI] [PubMed] [Google Scholar]
  • 24.Guide for the Care and Use of Laboratory Animals #86-23. Bethesda, MD: National Institutes of Health; 1985.
  • 25.Das MK, Bhattacharya A, Ghosal SK. Effect of different terpene-containing essential oils on percutaneous absorption of trazodone hydrochloride through mouse epidermis. Drug Deliv. 2006;13:425–431. doi: 10.1080/10717540500395064. [DOI] [PubMed] [Google Scholar]
  • 26.El Maghraby GM, Williams AC, Barry BW. Skin delivery of estradiol from deformable and traditional liposomes: mechanistic studies. J Pharm Pharmacol. 1999;51:1123–1134. doi: 10.1211/0022357991776813. [DOI] [PubMed] [Google Scholar]
  • 27.Warner RR, Myers MC, Taylor DA. Electron probe analysis of human skin: determination of the water concentration profile. J Invest Dermatol. 1988;90:218–224. doi: 10.1111/1523-1747.ep12462252. [DOI] [PubMed] [Google Scholar]
  • 28.Lasic D, Weiner N, Riaz M, Martin F. Liposomes. In: Lieberman A, Rieger M, Banker G, editors. Pharmaceutical Dosage Forms: Disperse Systems. vol 3. New York, NY: Marcel Dekker; 1998. pp. 43–86. [Google Scholar]
  • 29.Barry AL, Cullis PR. Direct NMR evidence for ethanol binding to the lipid-water interface of phospholipid bilayers. Biochemistry. 1994;33:8082–8088. doi: 10.1021/bi00192a013. [DOI] [PubMed] [Google Scholar]
  • 30.Maurer N, Wong KF, Stark H, et al. Spontaneous entrapment of polynucleotides upon electrostatic interaction with ethanol-destabilized cationic liposomes. Biophys J. 2001;80:2310–2326. doi: 10.1016/S0006-3495(01)76202-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Kulkarni SB, Singh M, Betageri GV. Encapsulation, stability and in vitro release characteristics of liposomal formulations of colchicine. J Pharm Pharmacol. 1997;49:491–495. doi: 10.1111/j.2042-7158.1997.tb06829.x. [DOI] [PubMed] [Google Scholar]
  • 32.El-Samaligy MS, Afifi NN, Mahmoud EA, Afify NN, Mahmoud EA. Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation. Int J Pharm. 2006;308:140–148. doi: 10.1016/j.ijpharm.2005.11.006. [DOI] [PubMed] [Google Scholar]
  • 33.El Sayed MA, Abdallah OY, Naggar VF, Khalafallah NM. Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int J Pharm. 2007;332:1–16. doi: 10.1016/j.ijpharm.2006.12.005. [DOI] [PubMed] [Google Scholar]
  • 34.Honeywell-Nguyen PL, Bouwstra JA. The in vitro transport of pergolide from surfactant-based elastic vesicles through human skin: a suggested mechanism of action. J Control Release. 2003;86:145–156. doi: 10.1016/S0168-3659(02)00415-7. [DOI] [PubMed] [Google Scholar]
  • 35.Cevc G. Lipid vesicles and other colloids as drug carriers on the skin. Adv Drug Deliv Rev. 2004;56:675–711. doi: 10.1016/j.addr.2003.10.028. [DOI] [PubMed] [Google Scholar]

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