Impeded Molecular Reorganization by Polyethylene Glycol Conjugation Revealed by X-ray Reflectivity and Diffraction Measurements

Abstract

Polyethylene glycol (PEG) coatings have been widely applied in pharmaceutical and biomedical systems to prevent nonspecific protein absorption, increase vesicle blood circulation time, and sustain drug release. This study systematically investigated the planar interfacial organization of phospholipid monolayers containing various amounts of PEG conjugations before and after enzyme-catalyzed degradation of the lipids using X-ray reflectivity and grazing incidence X-ray diffraction techniques. Results showed that attaching PEG to the headgroup of the lipids up to 15 mol % had limited effects on molecular packing of the lipid monolayers in the condensed phase at the gas−liquid interface and negligible effects on the enzyme adsorption to the interface. After enzyme-catalyzed degradation, equimolar fatty acids and lyso PC were generated. The fatty acids together with the subphase Ca 2+ self-assembled into highly organized multilayer domains at the interface. The X-ray measurements unambiguously revealed that the densely packed PEG markedly hindered microphase separation and formation of the palmitic acid−Ca 2+ complexes.

Knowledge-Based Design of 5-Fluororacil Prodrug Liposomal Formulation: Molecular Packing and Interaction Revealed by Interfacial Isotherms and X-ray Scattering Techniques

“…Therefore, the surface charges of the particles need to be shielded for biomedical applications. By adding 5% molar of PEGylated lipid DPPE-PEG5k, which has a limited effect on lipid molecular packing and interaction, the surface charge of the nanoparticles reduced to 4.14 ± 0.9 mV (which is considered neutral) from 30.6 ± 4.4 mV without the PEGylated lipid (Figure B), while the size remained at 90.4 ± 1.4 nm (Figure A).…”

“…The X-ray wavelength was 1.24 Å. Details of the experimental setup were described in our previous publications. − Briefly, a custom-made Langmuir trough (78 mm × 177.6 mm) with a single barrier was filled with 60 mL of PBS buffer. The trough is placed inside a gastight box.…”

“…Synchrotron X-ray reflectivity (XR) and grazing-incidence diffraction (GIXD) are powerful techniques to reveal the molecular interaction between the drug and lipid molecules, which provide the fundamental information for the judicious design of liposomal formulations embedding amphiphiles with high drug loading. We have previously employed XR and GIXD to reveal the spontaneous collapsing of the fatty acid after enzyme-catalyzed degradation of the phospholipid and evaluated the effects of polyethylene glycol (PEG) on enzyme adsorption and lipid degradation and reorganization. , By integrating a Langmuir trough with the synchrotron X-ray liquid surface scattering techniques, we systematically studied the monolayer packing of 5-FCPal and various lipids at the air–water interface. Five representative saturated and unsaturated lipids of different headgroup charges were employed in the study, including lipids with positively charged head groups (i.e., 1,2-stearoyl-3-trimethylammonium-propane (DSTAP) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)), neutral zwitterionic head groups (i.e., 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC)), and negatively charged head groups (i.e., 1,2-dipalmitoyl- sn -glycero-3-phospho-(1′-rac-glycerol) (DPPG)).…”

Self-assembled nanoformulations of paclitaxel for enhanced cancer theranostics

“…The promoiety plays a key role in the whole process of drug delivery, including blood circulation, tumor accumulation and penetration, cellular uptake and intracellular drug release. The hydrophilic segments, such as polypeptide, amino acid and zwitterionic molecules, can realize superior physiology stability and simultaneously avoid non-specific protein absorption in blood circulation 168 , 169 , 170 , 171 . Mu et al.…”