Chain length-dependent effects of alkylmaltosides on nasal absorption of enoxaparin.
The purpose of this study was to investigate whether the hydrophobic chain length of alkylmaltosides affects their efficacy as absorption promoters for nasally administered low-molecular-weight heparin and to study whether these agents enhance nasal absorption in a time-dependent manner without causing irreversible damage to the nasal epithelial membrane. For the nasal absorption studies, enoxaparin formulated with different alkylmaltosides was administered nasally to anesthetized rats and absorption of the drug was determined by measuring plasma anti-factor Xa activity. Reversibility studies were performed by administering enoxaparin at different time points after administration of alkylmaltosides. The AUC(0-360) for plasma anti-factor Xa-time curves increased with the increase in alkylmaltoside concentration in the formulations. Absolute and relative bioavailability of enoxaparin were increased by two-fold when the alkyl chain length of maltosides was increased from 8 to 14 carbons. Alkylmaltosides therefore increase nasal absorption of enoxaparin in a dose- and chain length-dependent manner. Of the alkylmaltosides tested, tetradecylmaltoside is the most potent enhancer of nasal absorption of enoxaparin. Longer chain alkylmaltosides produce a more prolonged effect on nasal mucosa compared with those with shorter alkyl chain.
Mustafa
Fatima
F
Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center School of Pharmacy, 1300 Coulter Drive, Amarillo, TX 79106, USA.
Yang
Tianzhi
T
Khan
Mansoor A
MA
Ahsan
Fakhrul
F
D000042:Absorption / Q000187:drug effects; D000281:Administration, Intranasal; D000818:Animals; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D009296:Nasal Cavity / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D017984:Enoxaparin; D008320:Maltose