PMID- 28377318 OWN - NLM STAT- MEDLINE DCOM- 20180105 LR - 20181202 IS - 1873-3476 (Electronic) IS - 0378-5173 (Linking) VI - 524 IP - 1-2 DP - 2017 May 30 TI - The effect of thermosensitive liposomal formulations on loading and release of high molecular weight biomolecules. PG - 279-289 LID - S0378-5173(17)30277-6 [pii] LID - 10.1016/j.ijpharm.2017.03.090 [doi] AB - Thermosensitive liposomes are clinically-relevant nanocarriers which have been used to deliver chemotherapeutic agents to tumors in combination with local hyperthermia. However, the encapsulation and release of macromolecular therapeutic agents (proteins, nucleic acids, bioactive polymers) is often hindered by their instability during the liposome formation as well as by the low encapsulation efficiency. The objective of this study was to investigate the influence of the thermosensitive liposomal formulation on the encapsulation and release of low and high molecular weight hydrophilic drugs, in order to identify the key parameters to control during nanocarrier design, depending on the specific drug delivery application. Thermosensitive liposomes with different formulations were prepared through the combinations of different lipids, including dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC), cholesterol (Chol), 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine (P-Lyso-PC), and the PEGylated lipid distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(PEG)-2000 (DSPE-PEG2000). The thin film hydration method was used for liposome preparation and loading of different water soluble molecules. The encapsulation efficiency and release profiles were investigated for a low molecular weight compound such as carboxyfluorescein (CF), proteins (albumin), and hydrophilic polymers which do not interact with the lipid bilayer, such as a linear dextran and a poly(ethylene glycol)-based star polymer. An optimised liposomal formulation [DPPC/P-lyso-PC/DSPE-PEG2000 90/10/4 (mol/mol) (LTSL)] was chosen for further application in encapsulating therapeutic proteins, such as lysozyme and the brain-derived neurotrophic factor (BDNF), which are recognized as drug carriers and potential therapeutic agents for kidney diseases and neurological disorders. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Huang, Xiaoyi AU - Huang X AD - Fondazione CEN - European Centre for Nanomedicine,Piazza Leonardo da Vinci 32, 20133 Milan, Italy; Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta". Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy. FAU - Li, Min AU - Li M AD - Fondazione CEN - European Centre for Nanomedicine,Piazza Leonardo da Vinci 32, 20133 Milan, Italy; Renal Research Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy. FAU - Bruni, Riccardo AU - Bruni R AD - Fondazione CEN - European Centre for Nanomedicine,Piazza Leonardo da Vinci 32, 20133 Milan, Italy; Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta". Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy. FAU - Messa, Piergiorgio AU - Messa P AD - Renal Research Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy. FAU - Cellesi, Francesco AU - Cellesi F AD - Fondazione CEN - European Centre for Nanomedicine,Piazza Leonardo da Vinci 32, 20133 Milan, Italy; Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta". Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy. Electronic address: francesco.cellesi@polimi.it. LA - eng PT - Journal Article DEP - 20170402 PL - Netherlands TA - Int J Pharm JT - International journal of pharmaceutics JID - 7804127 RN - 0 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Drug Carriers) RN - 0 (Lipids) RN - 0 (Liposomes) RN - 0 (Lysophosphatidylcholines) RN - 0 (Phosphatidylethanolamines) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - EC 3.2.1.17 (Muramidase) SB - IM MH - Brain-Derived Neurotrophic Factor/chemistry MH - Drug Carriers/*chemistry MH - Lipids/*chemistry MH - Liposomes/*chemistry MH - Lysophosphatidylcholines MH - Molecular Weight MH - Muramidase/chemistry MH - Phosphatidylethanolamines MH - Polyethylene Glycols MH - Temperature OTO - NOTNLM OT - BDNF OT - Lysozyme OT - Macromolecular drug delivery OT - Protein encapsulation OT - Thermosensitive liposomes EDAT- 2017/04/06 06:00 MHDA- 2018/01/06 06:00 CRDT- 2017/04/06 06:00 PHST- 2017/01/24 00:00 [received] PHST- 2017/03/28 00:00 [revised] PHST- 2017/03/31 00:00 [accepted] PHST- 2017/04/06 06:00 [pubmed] PHST- 2018/01/06 06:00 [medline] PHST- 2017/04/06 06:00 [entrez] AID - S0378-5173(17)30277-6 [pii] AID - 10.1016/j.ijpharm.2017.03.090 [doi] PST - ppublish SO - Int J Pharm. 2017 May 30;524(1-2):279-289. doi: 10.1016/j.ijpharm.2017.03.090. Epub 2017 Apr 2.