title: Synthesis, preformulation and liposomal formulation of cholesteryl carborane esters with various fatty chains.
abstract: The elevated expression of LDL receptor on tumor cells provides one attractive approach for targeted drug delivery to tumor cells. Suitable antitumor compounds, however, need to be synthesized and developed which mimic the native cholesteryl esters (as major constituent of LDL) in chemical structure for targeted delivery to tumor cells through the over-expressed LDL receptors. In the present study, new antitumor compounds were designed containing cholesterol, fatty chain and carborane which is used as the antitumor unit. Three new compounds were synthesized with a three-step reaction scheme. Similar to the native cholesteryl esters, these compounds are extremely hydrophobic and, before any further biological studies, suitable liposomal formulations for these new compounds are required. Various liposomal formulations as well as the preformulation characterization of these new compounds were thus examined. The incorporation efficiency of the compounds in liposomes was found to vary significantly depending on the type of fatty chain attached and the ratio of cholesterol:phospholipid used as the excipients of liposomal formulation.
authors.affiliation: Department of Pharmaceutical and Biomedical Science, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA.
authors.forename: Fars
authors.initials: F
authors.lastname: Alanazi
authors.forename: Hengguang
authors.initials: H
authors.lastname: Li
authors.forename: David S
authors.initials: DS
authors.lastname: Halpern
authors.forename: Svein
authors.initials: S
authors.lastname: Øie
authors.forename: D Robert
authors.initials: DR
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002788:Cholesterol Esters / Q000138:chemical synthesis* / Q000737:chemistry; D003460:Crystallization; D006361:Heating; D008081:Liposomes; D008970:Molecular Weight; D012995:Solubility
chemical_list: C477153:3-cholesteryl 12-(1-octenyl)-1,12-dicarba-closo-dodecaborane-1-carboxylate; C477154:3-cholesteryl 12-octadecyl-1,12-dicarba-closo-dodecaborane-1-carboxylate; C477152:3-cholesteryl 12-octyl-1,12-dicarba-closo-dodecaborane-1-carboxylate; D000970:Antineoplastic Agents; D001896:Boron Compounds; D002788:Cholesterol Esters; D008081:Liposomes