Relationships between Liposome Properties, Cell Membrane Binding, Intracellular Processing, and Intracellular Bioavailability
Journal Title: The AAPS Journal - Year 2011, Vol 13, Issue 4
Abstract
Positive surface charge enhances liposome uptake into cells. Pegylation, used to confer stealth properties to enable in vivo applications of cationic liposomes, compromises internalization. The goal of this study was to determine the quantitative relationships between these two liposome properties (separately and jointly), liposomes binding to cell membrane, and the subsequent internalization and residence in intracellular space (referred to as intracellular bioavailability). The results, obtained in pancreatic Hs-766T cancer cells, revealed nonlinear and inter-dependent relationships, as well as substantial qualitative and quantitative differences. The proportionality constant K of intracellular and membrane-bound liposomes at equilibrium (i.e., Ieq and Beq) showed a positive triphasic relationship with surface charge and a negative biphasic relationship with pegylation. Near-neutral liposomes showed little internalization of the membrane-bound moiety, increasing to a constant K value for medium charge liposomes (+15 to +35 mV zeta potential), followed by a further increase for highly charged liposomes (greater than or equal to +46 mV). The decline of pegylation with K value showed a breakpoint at 2%. The negative consequences of pegylation (%PEG) were partially offset by increasing charge (ZP). The best-fitting regression equations are: Beq = −1.36 × %PEG + 0.33 × ZP; Ieq = −1.52 × %PEG + 0.34 × ZP. It suggested that 1% pegylation increase can be offset with 4 mV ZP. The differences are such that it may be possible to balance these parameters to simultaneously maximize the stealth property and intracellular bioavailability of cationic liposomes.
Authors and Affiliations
Yinghuan Li, Jie Wang, Yue Gao, Jiabi Zhu, M. Guillaume Wientjes, Jessie L. -S. Au
Keywords
Related Articles
- EP ID EP681343
- DOI 10.1208/s12248-011-9298-1
- Views 71
- Downloads 0
Study of crystallization of endogenous surfactant in Eudragit NE30D-Free films and its influence on drug-release properties of controlled-release diphenhydramine HCI pellets coated with Eudragit NE30D
This study investigates the crystallization of the endogenous surfactant nonoxynol 100 in Eudragit NE30D-free films during storage and the influences of nonoxynol 100 on the dissolution of diphenhydramine hydrochloric ac...
Development of a Generic Anti-PEG Antibody Assay Using BioScale’s Acoustic Membrane MicroParticle Technology
Immunogenicity testing for PEGylated biotherapeutics should include methods to detect both anti-protein and anti-PEG antibodies (anti-PEG). Although some methods have been published for the detection of anti-PEG antibodi...
Application of the Modified Chi-Square Ratio Statistic in a Stepwise Procedure for Cascade Impactor Equivalence Testing
The online version of this article (doi:10.1208/s12248-014-9698-0) contains supplementary material, which is available to authorized users.
Cannabinoids, electrophysiology, and retrograde messengers: Challenges for the next 5 years
Most of the behavioral effects of cannabis and its active ingredients, the cannabinoids (Δ9THC being the most abundant of these), appear to be mediated by cannabinoid receptors. Endogenous cannabinoids (endocanna...
Effect of nonionic surfactant on transport of surface-active and non-surface-active model drugs and emulsion stability in triphasic systems