Interaction between PEG lipid and DSPE/DSPC phospholipids: An insight of PEGylation degree and kinetics of de-PEGylation

Donatella Paolino; Maria Lorena Accolla; Felisa Cilurzo; Maria Chiara Cristiano; Donato Cosco; Francesco Castelli; Maria Grazia Sarpietro; Massimo Fresta; Christian Celia

doi:10.1016/j.colsurfb.2017.04.018

Interaction between PEG lipid and DSPE/DSPC phospholipids: An insight of PEGylation degree and kinetics of de-PEGylation

Colloids Surf B Biointerfaces. 2017 Jul 1:155:266-275. doi: 10.1016/j.colsurfb.2017.04.018. Epub 2017 Apr 13.

Authors

Donatella Paolino¹, Maria Lorena Accolla², Felisa Cilurzo³, Maria Chiara Cristiano⁴, Donato Cosco⁵, Francesco Castelli⁶, Maria Grazia Sarpietro⁶, Massimo Fresta⁵, Christian Celia⁷

Affiliations

¹ Department of Experimental and Clinical Medicine, University of Catanzaro "Magna Graecia", Building of BioSciences, V.le Europa, I - 88100 Germaneto, Catanzaro, CZ, Italy; IRC-FSH-Interregional Research Center for Food Safety & Health, University of Catanzaro "Magna Græcia", Building of BioSciences, V.le Europa, I- 88100 Germaneto, Catanzaro, CZ, Italy.
² Department of Health Sciences, University of Catanzaro "Magna Graecia", Building of BioSciences, V.le Europa, I - 88100 Germaneto, Catanzaro, CZ, Italy; Department of Drug Sciences, University of Catania, V.le A. Doria 6, I - 95125 Catania, Italy.
³ Department of Pharmacy, University of Chieti - Pescara "G. d'Annunzio", Via dei Vestini 31, I - 66100 Chieti, Italy.
⁴ Department of Health Sciences, University of Catanzaro "Magna Graecia", Building of BioSciences, V.le Europa, I - 88100 Germaneto, Catanzaro, CZ, Italy.
⁵ IRC-FSH-Interregional Research Center for Food Safety & Health, University of Catanzaro "Magna Græcia", Building of BioSciences, V.le Europa, I- 88100 Germaneto, Catanzaro, CZ, Italy; Department of Health Sciences, University of Catanzaro "Magna Graecia", Building of BioSciences, V.le Europa, I - 88100 Germaneto, Catanzaro, CZ, Italy.
⁶ Department of Drug Sciences, University of Catania, V.le A. Doria 6, I - 95125 Catania, Italy.
⁷ Department of Pharmacy, University of Chieti - Pescara "G. d'Annunzio", Via dei Vestini 31, I - 66100 Chieti, Italy; Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA. Electronic address: c.celia@unich.it.

PMID: 28460301
DOI: 10.1016/j.colsurfb.2017.04.018

Abstract

The degree to which liposomes are PEGylated is the feature, which most influences the length of the presence of stealth liposomes in the bloodstream. In order to thoroughly investigate the maximum amount of DSPE-PEG₂₀₀₀ that can be used to stabilize stealth liposomes, these were synthesized at different concentrations of DSPE-PEG₂₀₀₀ and their physicochemical properties were investigated by using differential scanning calorimetry (DSC). The kinetics of PEGylation and de-PEGylation were performed by incubating non-stealth liposomes in a DSPE-PEG₂₀₀₀ suspension at different incubation times, and then analyzing the data using DSC and dynamic light scattering (DLS) techniques. The results demonstrated that DSPE-PEG₂₀₀₀ was self-assembled in the phospholipid bilayers, thus forming stealth liposomes. The different amounts of DSPE-PEG₂₀₀₀ in the bilayer triggered a de-PEGylation phenomenon, resulting in mixed nanoaggregates, which derived from the detergent-like properties of the PEGylated phospholipids.

Keywords: DSPE-PEG(2000) interaction; Differential scanning calorimetry; Dynamic light scattering; PEGylation; Stealth liposomes; de-PEGylation.

MeSH terms

Drug Stability
Kinetics
Liposomes / chemistry*
Phosphatidylcholines / chemistry*
Phosphatidylethanolamines / chemistry*
Polyethylene Glycols / chemistry*
Solutions

Substances

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)
Liposomes
Phosphatidylcholines
Phosphatidylethanolamines
Solutions
1,2-distearoylphosphatidylethanolamine
Polyethylene Glycols
1,2-distearoyllecithin