Thermodynamic and Physical Interactions between Novel Polymeric Surfactants and Lipids: Toward Designing Stable Polymer–Lipid Complexes

Abstract

Surfactant amphiphilic macromolecules (AMs) were complexed with a 1:1 ratio of 1,2-dioleoyl-3-trimethyl-ammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), either by a coevaporation (CE) or postaddition (PA) method, to form AM–lipid complexes with enhanced drug delivery applications. By characterizing the surfactant–lipid interactions, these heterogeneous drug delivery systems can be better controlled and engineered for optimal therapeutic outcomes. In this study, the physical interactions between DOPE:DOTAP liposomes and AM surfactants were investigated. Langmuir fllm balance and isothermal calorimetry studies showed cooperative intermolecular interactions between pure lipids and AM in monolayers and high thermostability of structure formed by the addition of AM micelles to DOTAP: DOPE vesicles in buffer solution respectively. Increasing the AM weight ratio in the complexes via the CE method led to complete vesicle solubilization—from lamellar aggregates, to a mixture of coexisting vesicles and micelles, to mixed micelles. Isothermal calorimetry evaluation of AM-lipid complexes shows that, at higher AM weight ratios, PA-produced complexes exhibit greater stability than complexes at lower AM weight ratios. Similar studies show that AM-lipid complexes produced by the CE methods display stronger interactions between AM-lipid components than complexes produced by the PA method. The results suggest that the PA method produces vesicles with AM molecules associated with its outer leaflet only (i.e., an AM-coated vesicle), while the CE method produces complexes ranging from mixed vesicles to mixed micelle in which the AM-lipid components are more intimately associated. These results will be helpful in the design of AM-lipid complexes as structurally defined, stable, and effective drug delivery systems.

Prediction of Micelle/Water and Liposome/Water Partition Coefficients Based on Molecular Dynamics Simulations, COSMO-RS, and COSMOmic

“…Liposomes and micelles can be regarded as potential drug delivery systems in research and industry . Consequently, numerous studies investigate novel micelle forming polymers as well as targeted uptake and release kinetics from nanostructured materials such as liposomes or micelles. − One of the crucial factors, representing the capacity of potential drug delivery systems, is the partition coefficient of a potential drug candidate between the aggregate and the surrounding water. Depending on the hydrophobicity of the solute, it partitions into different regions of the aggregate.…”

Carbohydrate-Derived Amphiphilic Macromolecules: A Biophysical Structural Characterization and Analysis of Binding Behaviors to Model Membranes

“…Lipid film was hydrated using 10 mM HEPES, MP Biomedical LLC (Aurora, OH, USA) for 1 mg/mL solutions with continuous shaking on an orbital reciprocating shaker for 1 h. Liposomes were produced by extruding through an Avanti mini-extruder system (Avanti Polar lipids) using 0.1 µm membrane filters, resulting in sizes averaging 100 nm after 21 passes. Liposomes were used within 10 h, stored at 4 °C [ 48 , 49 ]. Liposome sizes were measured using a Dynamic Light Scattering (DLS), NanoZS90 Instrument (Malvern Instruments, Malvern, UK).…”

Sugar-Based Amphiphilic Polymers for Biomedical Applications: From Nanocarriers to Therapeutics

“…The attractive intermolecular interaction between SBAP and lipid was illustrated by the observed condensation effect, in which the experimental molecular area negatively deviates from the ideal molecular area (i.e., no intermolecular interaction). These results indicated that SBAPs and lipids formed a stable mixture . To evaluate how serum impacts the size of SBAP–lipid complexes, dynamic light scattering (DLS) was used to monitor the complexes’ sizes over time.…”

“…These results indicated that SBAPs and lipids formed a stable mixture. 23 To evaluate how serum impacts the size of SBAP− lipid complexes, dynamic light scattering (DLS) was used to monitor the complexes' sizes over time. Complexes with low SBAP content underwent visible aggregation upon serum addition.…”