Effect of Charge and Molecular Weight on Transdermal Peptide Delivery by Iontophoresis

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2005 Sep 20

PMID 16170597

Citations 11

Authors

Nada Abla

Aarti Naik

Richard H Guy

Yogeshvar N Kalia

Affiliations

Soon will be listed here.

Abstract

Purpose: The study was conducted to investigate the impact of charge and molecular weight (MW) on the iontophoretic delivery of a series of dipeptides.

Methods: Constant current iontophoresis of lysine and 10 variously charged lysine- and tyrosine-containing dipeptides was performed in vitro.

Results: Increasing MW was compensated by additional charge; for example, Lys (MW = 147 Da, +1) and H-Lys-Lys-OH (MW = 275 Da, +2) had equivalent steady-state fluxes of 225 +/- 48 and 218 +/- 40 nmol cm(-2) h(-1), respectively. For peptides with similar MW, e.g., H-Tyr-D-Arg-OH (MW = 337 Da, +1) and H-Tyr-D-Arg-NH(2) (MW = 336 Da, +2), the higher valence ion displayed greater flux (150 +/- 26 vs. 237 +/- 35 nmol cm(-2) h(-1)). Hydrolysis of dipeptides with unblocked N-terminal residues, after passage through the stratum corneum, suggested the involvement of aminopeptidases. The iontophoretic flux of zwitterionic dipeptides was less than that of acetaminophen and dependent on pH.

Conclusions: For the series of dipeptides studied, flux is linearly correlated to the charge/MW ratio. Data for zwitterionic peptides indicate that they do not behave as neutral ("charge-less") molecules, but that their iontophoretic transport is dependent on the relative extents of ionization of the constituent ionizable groups, which may also be affected by neighboring amino acids.

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References

Kalia Y, Naik A, Garrison J, Guy R . Iontophoretic drug delivery. Adv Drug Deliv Rev. 2004; 56(5):619-58. DOI: 10.1016/j.addr.2003.10.026. View

Suzuki Y, Iga K, Yanai S, Matsumoto Y, Kawase M, Fukuda T . Iontophoretic pulsatile transdermal delivery of human parathyroid hormone (1-34). J Pharm Pharmacol. 2001; 53(9):1227-34. DOI: 10.1211/0022357011776676. View

Chang J, Knecht R, Braun D . A complete separation of dimethylaminoazobenzenesulphonyl-amino acids. Amino acid analysis with low nanogram amounts of polypeptide with dimethylaminoazobenzenesulphonyl chloride. Biochem J. 1982; 203(3):803-6. PMC: 1158301. DOI: 10.1042/bj2030803. View

Nakamura K, Katagai K, Mori K, Higo N, Sato S, Yamamoto K . Transdermal administration of salmon calcitonin by pulse depolarization-iontophoresis in rats. Int J Pharm. 2001; 218(1-2):93-102. DOI: 10.1016/s0378-5173(01)00615-9. View

Lee K, Fitch C, Lecomte J, Garcia-Moreno E B . Electrostatic effects in highly charged proteins: salt sensitivity of pKa values of histidines in staphylococcal nuclease. Biochemistry. 2002; 41(17):5656-67. DOI: 10.1021/bi0119417. View

Marro D, Kalia Y, Delgado-Charro M, Guy R . Contributions of electromigration and electroosmosis to iontophoretic drug delivery. Pharm Res. 2002; 18(12):1701-8. DOI: 10.1023/a:1013318412527. View

Marro D, Guy R, Delgado-Charro M . Characterization of the iontophoretic permselectivity properties of human and pig skin. J Control Release. 2001; 70(1-2):213-7. DOI: 10.1016/s0168-3659(00)00350-3. View

Maseda C, Fukui Y, Kimura K, Matsubara K . Chromophoric labeling of cannabinoids with 4-dimethylaminoazobenzene-4'-sulfonyl chloride. J Forensic Sci. 1983; 28(4):911-21. View

Santi P, Colombo P, Bettini R, Catellani P, Minutello A, Volpato N . Drug reservoir composition and transport of salmon calcitonin in transdermal iontophoresis. Pharm Res. 1997; 14(1):63-6. DOI: 10.1023/a:1012055401038. View

10.

Suzuki Y, Nagase Y, Iga K, Kawase M, Oka M, Yanai S . Prevention of bone loss in ovariectomized rats by pulsatile transdermal iontophoretic administration of human PTH(1-34). J Pharm Sci. 2002; 91(2):350-61. DOI: 10.1002/jps.10019. View

11.

Santi P, Volpato N, Bettini R, Catellani P, Massimo G, Colombo P . Transdermal iontophoresis of salmon calcitonin can reproduce the hypocalcemic effect of intravenous administration. Farmaco. 1997; 52(6-7):445-8. View

12.

Wang S, Tham S, Poon M . Thin-layer chromatographic and column liquid chromatographic analyses of morphine in urine via dabsylation. J Chromatogr. 1986; 381(2):331-41. DOI: 10.1016/s0378-4347(00)83599-9. View

13.

Bi M, Singh J . Stability of luteinizing hormone releasing hormone: effects of pH, temperature, pig skin, and enzyme inhibitors. Pharm Dev Technol. 2000; 5(3):417-22. DOI: 10.1081/pdt-100100558. View

14.

Edgcomb S, Murphy K . Variability in the pKa of histidine side-chains correlates with burial within proteins. Proteins. 2002; 49(1):1-6. DOI: 10.1002/prot.10177. View

15.

Chang J, Knecht R, Braun D . Amino acid analysis at the picomole level. Application to the C-terminal sequence analysis of polypeptides. Biochem J. 1981; 199(3):547-55. PMC: 1163409. DOI: 10.1042/bj1990547. View

16.

Knecht R, Chang J . Liquid chromatographic determination of amino acids after gas-phase hydrolysis and derivatization with (dimethylamino)azobenzenesulfonyl chloride. Anal Chem. 1986; 58(12):2375-9. DOI: 10.1021/ac00125a006. View

17.

Steigleder G, KUDICKE R, Kamei Y . [Localization of aminopeptidase activity in normal skin]. Arch Klin Exp Dermatol. 1962; 215:307-25. DOI: 10.1007/BF00693555. View

18.

Boderke P, Merkle H, Cullander C, Ponec M, Bodde H . Localization of aminopeptidase activity in freshly excised human skin: direct visualization by confocal laser scanning microscopy. J Invest Dermatol. 1997; 108(1):83-6. DOI: 10.1111/1523-1747.ep12285642. View

19.

Chang S, Hofmann G, Zhang L, Deftos L, Banga A . Transdermal iontophoretic delivery of salmon calcitonin. Int J Pharm. 2000; 200(1):107-13. DOI: 10.1016/s0378-5173(00)00351-3. View

20.

Glikfeld P, Cullander C, Hinz R, Guy R . A new system for in vitro studies of iontophoresis. Pharm Res. 1988; 5(7):443-6. DOI: 10.1023/a:1015944619348. View