Phase Structures of a Hydrated Anionic Phospholipid Composition Containing Cationic Dendrimers and Pegylated Lipids

Abstract

The effect of 4th generation poly(amidoamine) dendrimer (4G PAMAM) present in an anionic phospholipid composition, consisting of hydrogenated soyphosphatidylcholine (HSPC), cholesterol (CH), dicetyl phosphate (DCP), and poly(ethylene glycol) (Mw approximately 2000) derivatized phosphatidylethanolamine (PEG2000-PE), on the hydration and liquid crystalline structure formation was investigated. The optical and polarized light microscopies of the liposomal dispersion obtained from the hydrated lipid composition show two types of birefringent structures (mesophases): plastic, wormlike microstructures and conventional, over-elongated lamellae. Differential scanning calorimetry (DSC) shows an increase in the liquid crystalline phase transition (Tg) of the lipid composition from 60 to 94 degrees C with increasing 4G PAMAM concentrations from 0 to 0.011 mM, respectively. The Tg values of the two microstructures were 68 and 84 degrees C, respectively, indicating that the plastic microstructures were 4G PAMAM/DCP-complexes-rich (alpha mesophases) and the conventional and elongated lamellae were dendrimer-doped HSPC/CH-rich microstructures (beta mesophases). Optical microscopy shows that the alpha mesophases convert into various other types of vesicular structures such as giant unilamellar vesicles and biliquid foams, upon heating above the phase transition temperature of the lipid composition (approximately 60-65 degrees C). The microstructure transformation is a result of an osmotic influx of water and the detergent action of PEG2000-PE present in the lipid composition. The transmission electron microscopy (TEM) images of the liposomal dispersion show particles embedding circular transparent domains that exactly correlate to the theoretical 4G PAMAM/DCP complex sizes, thus, providing evidence of 4G PAMAM interspersed within the two mesophases. Small-angle X-ray scattering (SAXS) measurements indicate that the alpha mesophases are a dendrimer-interlinked, symmetrically undulated lamellar phase and the beta mesophases are dendrimer-doped, occasionally kinked lamellae. An increase in dendrimer concentration in the lipid composition was found to decrease interlamellar spacing. On the basis of optical microscopy, DSC, TEM, and SAXS data, a model of dendrimer-doped mesophase structure and lamellae fusion is proposed. This investigation provides new self-assembled materials for drug/gene delivery and supplements the understanding of mechanisms involved in various biological processes such as membrane fusion, transmembrane permeation, and endocytosis.

Effects of PAMAM dendrimers with various surface functional groups and multiple generations on cytotoxicity and neuronal differentiation using human neural progenitor cells

“…These reports suggest that dendrimer-induced cytotoxicity may cause by the surface charge of the dendrimers. Positively charged dendrimers are likely to react with negative charges on lipid membranes, and their reactions pull together two anionic lipid layers, resulting in cytotoxicity (Jain et al, 2010;Khopade et al, 2004). Our results for different surface group PAMAM dendrimers in the present study (Fig.…”

Microsponges: Topical Preparation and Its Applications

“…Benzoyl peroxide Maintained efficacy with decreased skin irritation and sensitization. [37] Anti-inflammatory: E.g. hydrocortisone Long lasting activity with reduction of skin allergic response and dermatoses.…”

Physico-chemical Studies on the Interaction of Dendrimers with Lipid Bilayers. 1. Effect of Dendrimer Generation and Liposome Surface Charge

“…The dendrimers, due to their unique structure, different from the usual/conventional polymers, possess special features. For example, the cavity/cage inside the dendrimer core, can host small molecules, may it be drug or metallic clusters 7 . The dendrimers have a predominant spherical/globular structure, for which they have low viscosity compared to the corresponding linear polymers.…”