Sonvico Fabio, Colombo Gaia, Gallina Laura, Bortolotti Fabrizio, Rossi Alessandra, McInnes Colin J, Massimo Gina, Colombo Paolo, Scagliarini Alessandra
Department of Pharmacy, University of Parma, Viale G.P. Usberti, 27/a, Parma, 43100, Italy.
AAPS J. 2009 Jun;11(2):242-9. doi: 10.1208/s12248-009-9101-8. Epub 2009 Apr 21.
The aim of the research was to study a new cidofovir/sucralfate drug product to be used as a spray for treating the mucosal and/or skin lesions. The product, i.e., a water suspension of sucralfate (15% w/w) and cidofovir (1% w/w), combines the potent antiviral activity of the acyclic nucleoside phosphonate cidofovir ((S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine) and the wound healing properties of sucralfate gel (sucrose octasulphate basic aluminum salt). The product was characterized in vitro with respect to compatibility between drug and carrier, spray particle size, spray deposition, drying kinetics, and drug content and release. An interaction between the two active substances was found. The interaction between sucralfate and cidofovir was counteracted by introducing sodium dihydrogen phosphate (16% w/w) in the preparation. The spray formulation containing cidofovir/sucralfate gel painted the skin and dried quickly to a scab, remaining firmly adhered to the lesions. The therapeutic paint was tested in vivo on lambs infected with orf virus by treating the animals with different cidofovir/sucralfate formulations (0.5% or 1% cidofovir + sucralfate 15% + NaH(2)PO(4) 16% w/w) and with sucralfate gel suspension alone as control. The treatment with formulations containing cidofovir and phosphate salt for four consecutive days resulted in a rapid resolution of the lesions, with scabs containing significantly lower amounts of viable virus when compared with untreated lesions and lesions treated with sucralfate suspension alone.
该研究的目的是研究一种新的西多福韦/硫糖铝药物产品,用作喷雾剂来治疗粘膜和/或皮肤损伤。该产品,即硫糖铝(15%w/w)和西多福韦(1%w/w)的水悬浮液,结合了无环核苷膦酸西多福韦((S)-1-[3-羟基-2-(膦酰甲氧基)丙基]胞嘧啶)的强效抗病毒活性和硫糖铝凝胶(蔗糖八硫酸碱式铝盐)的伤口愈合特性。该产品在体外就药物与载体的相容性、喷雾粒径、喷雾沉积、干燥动力学以及药物含量和释放进行了表征。发现了两种活性物质之间的相互作用。通过在制剂中引入磷酸二氢钠(16%w/w)来抵消硫糖铝和西多福韦之间的相互作用。含有西多福韦/硫糖铝凝胶的喷雾制剂涂抹在皮肤上并迅速干燥结痂,牢固地附着在损伤处。通过用不同的西多福韦/硫糖铝制剂(0.5%或1%西多福韦+15%硫糖铝+16%w/w磷酸二氢钠)以及单独使用硫糖铝凝胶悬浮液作为对照对感染了羊口疮病毒的羔羊进行体内治疗,对这种治疗性涂料进行了测试。连续四天用含有西多福韦和磷酸盐的制剂进行治疗导致损伤迅速消退,与未治疗的损伤以及仅用硫糖铝悬浮液治疗的损伤相比,结痂中活病毒的含量显著降低。