Interaction of cremophor EL with human plasma

Area of Science:

• Biochemistry
• Pharmacology
• Analytical Chemistry

Background:

• Cremophor EL (CRM) is a widely used pharmaceutical excipient.
• Understanding CRM's interaction with plasma components is crucial for drug formulation and delivery.
• Lipoproteins play key roles in lipid transport and are potential interaction partners for excipients.

Purpose of the Study:

• To investigate the interaction between cremophor EL (CRM) and human plasma lipoproteins (VLDL, LDL, HDL) and nonlipoprotein components.
• To determine how CRM affects the physical properties and distribution of these plasma proteins.
• To assess the binding capacity and potential alterations induced by varying CRM concentrations.

Main Methods:

• Ultracentrifugation was employed to separate and analyze human plasma lipoproteins.
• CRM was added at various concentrations to plasma samples.
• Changes in lipoprotein density, distribution, and optical absorption were measured to assess interactions.

Main Results:

• Very-low-density lipoproteins (VLDL) showed negligible binding capacity for CRM.
• Low-density lipoproteins (LDL) may act as carriers for CRM, but without significant protein alteration.
• High-density lipoproteins (HDL) exhibited density shifts and particle destruction at higher CRM concentrations, forming bimodal distributions.
• Human serum albumin (HSA) and other heavy proteins were unaffected by CRM, even at high concentrations.

Conclusions:

• CRM exhibits differential interactions with human plasma lipoproteins.
• HDL is particularly sensitive to CRM, undergoing structural modifications.
• LDL's role as a potential CRM carrier warrants further investigation.
• The selective interaction of CRM with lipoproteins may have implications for drug delivery and pharmacokinetic profiles.