title: Formulation optimization and in vivo proof-of-concept study of thermosensitive liposomes balanced by phospholipid, elastin-like polypeptide, and cholesterol.
abstract: One application of nanotechnology in medicine that is presently being developed involves a drug delivery system (DDS) employing nanoparticles to deliver drugs to diseased sites in the body avoiding damage of healthy tissue. Recently, the mild hyperthermia-triggered drug delivery combined with anticancer agent-loaded thermosensitive liposomes was widely investigated. In this study, thermosensitive liposomes (TSLs), composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG), cholesterol, and a fatty acid conjugated elastin-like polypeptide (ELP), were developed and optimized for triggered drug release, controlled by external heat stimuli. We introduced modified ELP, tunable for various biomedical purposes, to our thermosensitive liposome (e-TSL) to convey a high thermoresponsive property. We modulated thermosensitivity and stability by varying the ratios of e-TSL components, such as phospholipid, ELP, and cholesterol. Experimental data obtained in this study corresponded to results from a simulation study that demonstrated, through the calculation of the lateral diffusion coefficient, increased permeation of the lipid bilayer with higher ELP concentrations, and decreased permeation in the presence of cholesterol. Finally, we identified effective drug accumulation in tumor tissues and antitumor efficacy with our optimized e-TSL, while adjusting lag-times for systemic accumulation.
authors: Drug Delivery System Group, Bio Research Center, Samsung Advanced Institute of Technology (SAIT), Yongin, Gyeonggi-do, South Korea.
authors: Sun Min
authors: SM
authors: Park
authors: Drug Delivery System Group, Bio Research Center, Samsung Advanced Institute of Technology (SAIT), Yongin, Gyeonggi-do, South Korea.
authors: Jae Min
authors: JM
authors: Cha
authors: Drug Delivery System Group, Bio Research Center, Samsung Advanced Institute of Technology (SAIT), Yongin, Gyeonggi-do, South Korea.
authors: Jungyong
authors: J
authors: Nam
authors: Drug Delivery System Group, Bio Research Center, Samsung Advanced Institute of Technology (SAIT), Yongin, Gyeonggi-do, South Korea.
authors: Min Sang
authors: MS
authors: Kim
authors: Drug Delivery System Group, Bio Research Center, Samsung Advanced Institute of Technology (SAIT), Yongin, Gyeonggi-do, South Korea.
authors: Sang-Jun
authors: SJ
authors: Park
authors: Drug Delivery System Group, Bio Research Center, Samsung Advanced Institute of Technology (SAIT), Yongin, Gyeonggi-do, South Korea.
authors: Eun Sung
authors: ES
authors: Park
authors: Department of Chemical Engineering, Dankook University, Yongin, Gyeonggi-do, South Korea.
authors: Hwankyu
authors: H
authors: Lee
authors: Drug Delivery System Group, Bio Research Center, Samsung Advanced Institute of Technology (SAIT), Yongin, Gyeonggi-do, South Korea.
authors: Hyun Ryoung
authors: HR
authors: Kim
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D013816:Thermodynamics; D044366:Transition Temperature; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides; D010743:Phospholipids; D004317:Doxorubicin; D002784:Cholesterol