title: Ultrasound effects on brain-targeting mannosylated liposomes: in vitro and blood-brain barrier transport investigations.
abstract: Delivering drugs to intracerebral regions can be accomplished by improving the capacity of transport through blood-brain barrier. Using sertraline as model drug for brain targeting, the current study aimed at modifying its liposomal vesicles with mannopyranoside. Box-Behnken design was employed to statistically optimize the ultrasound parameters, namely ultrasound amplitude, time, and temperature, for maximum mannosylation capacity, sertraline entrapment, and surface charge while minimizing vesicular size. Moreover, in vitro blood-brain barrier transport model was established to assess the transendothelial capacity of the optimized mannosylated vesicles. Results showed a dependence of vesicular size, mannosylation capacity, and sertraline entrapment on cavitation and bubble implosion events that were related to ultrasound power amplitude, temperature. However, short ultrasound duration was required to achieve >90% mannosylation with nanosized vesicles (<200 nm) of narrow size distribution. Optimized ultrasound parameters of 65°C, 27%, and 59 seconds for ultrasound temperature, amplitude, and time were elucidated to produce 81.1%, 46.6 nm, and 77.6% sertraline entrapment, vesicular size, and mannosylation capacity, respectively. Moreover, the transendothelial ability was significantly increased by 2.5-fold by mannosylation through binding with glucose transporters. Hence, mannosylated liposomes processed by ultrasound could be a promising approach for manufacturing and scale-up of brain-targeting liposomes.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Zidan
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Hibah
authors.initials: H
authors.lastname: Aldawsari
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D042783:Endothelial Cells / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D010316:Particle Size; D011485:Protein Binding; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D020280:Sertraline / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D013997:Time Factors; D014465:Ultrasonics
chemical_list: D000928:Antidepressive Agents; D004337:Drug Carriers; D051246:Glucose Transport Proteins, Facilitative; D008055:Lipids; D008358:Mannose; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
keywords: CNS delivery; lipid based formulations; quality by design; sertraline hydrochloride; sizing