Preparation and characterization of liposomal formulations of neurotensin-degrading enzyme inhibitors.
Neurotensin-degrading enzyme (NTDE) inhibitors hold great potential for treating psychotic disorders. However, brain uptake of such compounds in vivo is generally low due to the presence of the blood-brain barrier. In this study, liposomal formulations of two NTDE inhibitors, named compound 1 (C1) and compound 2 (C2) were prepared. Association of these compounds with the liposomal bilayer, subsequent liposomal stability, and compound release in the presence of albumin was studied. Entrapment of the compounds in the liposomal bilayer showed the solubilizing properties of the liposomes. Size and polydispersity index of the compound-entrapped liposomes did not change over 1 month, showing colloidal stability of the liposomal drug formulations. The amount of compounds associated with the liposomes decreased within one day. After this, the association remained stable at 4°C. For C1, association remained stable at 37°C in HEPES buffered saline, and the compound was gradually released in the presence of bovine serum albumin. For C2, the release was rapid in both HBS and BSA at 37°C. In conclusion, the formulation of NTDE inhibitors C1 and C2 in liposomes has been demonstrated and holds promise to deliver NTDE inhibitors in vivo.
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands. i.vanrooy@uu.nl
Inge
I
van Rooy
Shin-Ying
SY
Wu
Gert
G
Storm
Wim E
WE
Hennink
Heike
H
Dinter-Heidorn
Raymond M
RM
Schiffelers
Enrico
E
Mastrobattista
D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000737:chemistry; D004355:Drug Stability; D004356:Drug Storage; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D006531:HEPES / Q000737:chemistry; D008081:Liposomes; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry; D012995:Solubility; D013696:Temperature
D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D008081:Liposomes; D012710:Serum Albumin, Bovine; D012965:Sodium Chloride; D008666:Metalloendopeptidases; C045334:neurotensin-degrading enzyme; D006531:HEPES