Priprava pegiliranih nano-liposomskih formulacija sa SN-38: In vitro karakterizacija i in vivo biodistribucija u miševa

7-Ethyl-10-hydroxy-camptothecin (SN38), a metabolite of irinotecan × HCl, is poorly soluble in aqueous solutions and practically insoluble in most physiologically compatible and pharmaceutically acceptable solvents. Formulation of SN38 in concentrated pharmaceutical delivery systems for parenteral administration is thus very difficult. Due to their biocompatibility and low toxicity, liposomes were considered for the delivery of SN38. In this study, pegylated liposomes with distearoylphosphatidylcholine, distearoylphosphatidylethanolamine containing SN38 were prepared and their characteristics, such as particle size, encapsulation efficiency, in vitro drug release and biodistribution, were investigated. The particle size of liposomes was in the range of 150200 nm. The encapsulation efficiency and in vitro release rate of pegylated liposomes was higher than those of non-pegylated liposomes. As expected, the distribution of pegylated liposomes in body organs such as liver, kidney, spleen and lung was considerably lower than that of non-pegylated liposomes. Also, their blood concentration was at least 50 % higher than that of non-pegylated liposomes.7-Etil-10-hidroksi-kamptotecin (SN38), metabolit irinotekan hidroklorida, vrlo je slabo topljiv u vodenim otopinama i praktički netopljiv u većini fiziološki kompatibilnih i farmaceutski prihvatljivih otapala. Poradi toga je veoma teško formuliranje supstancije SN38 u koncentrirane sustave za parenteralnu primjenu. Liposomi se zbog svoje biokompatibilnosti i niske toksičnosti čine pogodnim za isporuku SN38. U ovom radu opisana je priprava pegiliranih liposoma sa SN38 pomoću distearoilfosfatidilkolina i distearoilfosfatidiletanolamina. Pripravljenim liposomima određena je veličina čestica, sposobnost inkapsuliranja, in vitro oslobađanje i biodistribucija. Veličina čestica liposoma bila je u rasponu 150200 nm. Sposobnost kapsuliranja i in vitro oslobađanje pegiliranih liposoma bila je veća nego nepegiliranih liposoma. Kao što se očekivalo, distribucija pegiliranih liposoma u jetri, bubregu, slezeni i plućima bila je značajno niža nego nepegiliranih liposoma. Njihova koncentracija u krvi bila je najmanje 50 % viša od nepegiliranih liposoma