Merclin N, Bender J, Sparr E, Guy R H, Ehrsson H, Engström S
Department of Pharmacy, Uppsala Biomedical Centre, Uppsala University, Uppsala, Sweden.
J Control Release. 2004 Nov 24;100(2):191-8. doi: 10.1016/j.jconrel.2004.08.025.
The hydrochloride salts of 5-aminolevulinic acid (ALA) and its methyl ester (m-ALA), respectively, were dissolved in a lipid sponge phase comprising monoolein, propylene glycol and aqueous buffer at concentrations of approximately 0.25% and 16% w/w m-ALA. The iontophoretic and passive delivery of ALA and m-ALA from this formulation through porcine skin in vitro were measured and compared to formulations used in clinical practice, 20% w/w ALA in Unguentum M and Metvix (a cream containing 16% w/w m-ALA). A sponge phase with 16% w/w m-ALA showed a higher passive flux (approximately 140 nmol cm(-2) h(-1) at 5 h) but a lower iontophoretic flux (approximately 800 nmol cm(-2) h(-1) at 5 h) compared to the clinically used products but the differences are hardly significant due to large standard deviations. ALA and m-ALA in sponge phase formulation showed iontophoretic fluxes in the range 80-100 nmol cm(-2) h(-1) at 3 h, i.e. values comparable to the passive fluxes from the more concentrated vehicles. The results demonstrate that the lipid sponge phase, a thermodynamically stable liquid with amphiphilic character, may have potential as a transdermal drug delivery vehicle.
分别将5-氨基乙酰丙酸（ALA）及其甲酯（m-ALA）的盐酸盐溶解于由单油酸甘油酯、丙二醇和水性缓冲液组成的脂质海绵相中，m-ALA的浓度约为0.25%和16%（w/w）。测定了ALA和m-ALA从该制剂通过猪皮的体外离子电渗和被动给药情况，并与临床实践中使用的制剂进行比较，即Unguentum M中20%（w/w）的ALA和Metvix（一种含有16%（w/w）m-ALA的乳膏）。与临床使用的产品相比，含16%（w/w）m-ALA的海绵相显示出更高的被动通量（5小时时约为140 nmol cm⁻² h⁻¹）但更低的离子电渗通量（5小时时约为800 nmol cm⁻² h⁻¹），不过由于标准偏差较大，差异不太显著。海绵相制剂中的ALA和m-ALA在3小时时的离子电渗通量范围为80 - 100 nmol cm⁻² h⁻¹，即与来自更浓缩载体的被动通量相当。结果表明，脂质海绵相这种具有两亲性的热力学稳定液体，可能具有作为透皮给药载体的潜力。
