Lipidic particles

In contrast, the carotenes such as p-carotene and lycopene may position themselves parallel to the membrane surfaces to remain in a more lipophilic environment in the inner cores of the bilayer membranes. To move through an aqueous environment, carotenoids can be incorporated into lipid particles such as mixed micelles in the gut lumen or lipoproteins in the blood circulation and they can also form complexes with proteins with unspecific or specific bindings. 

To enhance lipid particle clearance by acting as a cofactor for the lipoprotein lipase enzyme... 

A reduction in the electrical charge is known to increase the flocculation and coalescence rates. Sufficient high zeta potential (> — 30 mV) ensures a stable emulsion by causing repulsion of adjacent droplets. The selection of suitable surfactants can help to optimize droplet surface charges and thus enhance emulsion stability. Lipid particles with either positive or negative surface charges are more stable and are cleared from the bloodstream more rapidly than those with neutral charge [192, 193]. 

Westesen and Siekmann [11] used suspensions of colloidal solid lipid particles as well as lyophilizates as delivery systems for the parenteral administration of the drug for its particle morphology determination. 

Figure 6 Encapsulation of plasmid DNA (pDNA) in small sterically stabilized liposomes [stabilized plasmid-lipid particles (SPLP)] using a detergent dialysis procedure. (A) Entrapped pDNA-to-lipid ratio as a function of the initial pDNA-to-lipid ratio (mg/mg). The initial lipid concentration was lOmg/mL. (B) Cryo-electron micrograph showing the structure of SPLP. The location of the plasmid is indicated by the striated pattern superimposed on the liposomes. The bar represents 100 nm.

Figure 7 Pharmacokinetic properties and in vivo gene expression of stabilized plasmid-lipid particles (SPLP). (A) The levels of intact plasmid DNA (pDNA) in the circulation resulting from IV injection of naked plamid pDNA ( ), lipoplexes (O), and SPLP ( ) were determined by Southern blot analysis of plasma samples (100 pg pDNA/mouse). (B) Transgene expression at a distal tumor site resulting from rv injection of naked plamid pDNA ( ), plamid pDNA-cationic liposome complexes (O), and SPLP ( ).

Tam P, Monck M, Lee D, et al. Stabilized plasmid-lipid particles for systemic gene therapy. Gene Ther 2000 7 1867. 

Saravolac EG, Ludkovski O, Skirrow R, et al. Encapsulation of plasmid DNA in stabilized plasmid-lipid particles composed of different cationic lipid concentration for optimal transfection activity. J Drug Target 2000 7 423. 

Fenske DB, MacLachlan I, Cullis PR. Stabilized plasmid-lipid particles a systemic gene therapy vector. In Phillips MI, ed. Methods in Enzymology Gene Therapy Methods. Vol. 346. San Diego, CA, U.S.A. Academic Press Inc., 2002 36-71. 

Mui B, Raney SG, Semple SC, Hope MJ. Immune stimulation by a CpG-containing oligodeoxynucleotide is enhanced when encapsulated and delivered in lipid particles. J Pharmacol Exp Ther 2001 298 1185. 

Mok KW, Lam AM, Cullis PR. Stabilized plasmid-lipid particles factors influencing plasmid entrapment and transfection properties. Biochim Biophys Acta 1999 1419 137. 

Heurtault B, Saulnier P, Pech B, et al. Physico-chemical stability of colloidal lipid particles. Biomaterials 2003 24(23) 4283. 

Lipid particles can also be prepared by dispersing a hot microemulsion in cold water (2 to 3°C) under stirring. Drawbacks of this process are the frequent need for organic solvents and the relative low particle concentration as a result of the dilution with water [14]. 

The interpretation of in vitro drng release prohles also has to take the specific in vivo environment into account. Then a possible enzymatic degradation of lipid particles may be influenced to a relevant extent by the composition of the particles [31]. 

If SLN are incorporated into vehicles, interactions with the vehicle constituents may induce physical instabilities such as dissolution or aggregation of lipid particles. Therefore, during storage, particle sizes and the solid character of the particles have to be followed. 

Following the evaporation of water from the lipid nanodispersion applied to the skin surface, lipid particles form an adhesive layer, applying occlusion to the surface [17,40]. Therefore, the hydration of the stratum comeum may increase, which can facilitate drug penetration into deeper skin strata and even systemic availability of the drug. Occlusive effects are strongly related to particle size. Nanoparticles have turned out 15-fold more occlusive than microparticles [17], and particles smaller than 400 nm in a dispersion containing at least 35% high-crystallinity lipid proved to be most potent [41]. 

Solidification of the particles may not be the final step in the formation process of solid lipid particles. Lipidic materials exhibit rich polymorphism [69,70], which may also occur in the dispersed state. In nanoparticles, the polymorphic behavior of the matrix lipids may, however, differ distinctly from that in the bulk material. Polymorphic transitions are usually accelerated in the nanoparticles compared with the bulk lipids [2,62]. In some cases, polymorphic forms not observable in the corresponding bulk materials were detected in lipid nanoparticles [1,65]. Because polymorphism can affect pharmaceutically relevant properties of the particles, such as the drug incorporation capacity [65], corresponding investigations should also be included in the characterization process. As long as polymorphic or other crystalaging phenomena have not terminated, the particle matrix cannot be regarded as static, and alterations of the particle properties may still occur. 

Differential scanning calorimetry (DSC) and x-ray diffraction (XRD) are the techniques most widely used for the characterization of crystallinity and polymorphism of solid lipid particles. Although DSC is usually more sensitive in detecting crystalline material, XRD is much more reliable in determining the type of polymorph present in the dispersions because it provides structural data. In contrast, DSC can detect the type of polymorph only indirectly via the transition temperatures and enthalpies. Because these parameters may be different from those observed in the bulk material, particularly for small colloidal particles [1,62], assigmnent of polymorphic forms in DSC curves should be supported by x-ray data. 

In DSC the sample is subjected to a controlled temperature program, usually a temperature scan, and the heat flow to or from the sample is monitored in comparison to an inert reference [75,76], The resulting curves — which show the phase transitions in the monitored temperature range, such as crystallization, melting, or polymorphic transitions — can be evaluated with regard to phase transition temperatures and transition enthalpy. DSC is thus a convenient method to confirm the presence of solid lipid particles via the detection of a melting transition. DSC recrystaUization studies give indications of whether the dispersed material of interest is likely to pose recrystallization problems and what kind of thermal procedure may be used to ensure solidification [62-65,68,77]. 

Baeza, L, Wong, C., Mondragon, R., etal. (1994). Transbilayer diffusion of divalent cations into liposomes mediated by lipidic particles of phosphatidate, / Mol. EvoL, 39, 560-8. 

Bot, A.I., D.J. Smith, S. Bot, L. Dellamary, T.E. Tarara, S. Harders, W. Phillips, J.G Weers, and C.M. Woods, Receptor-mediated targeting of spray-dried lipid particles coformulated with immunoglobulin and loaded with a prototype vaccine. Pharm Res, 2001.18(7) 971-9. 

FIGURE 10.3 Schematic presentation of lipid based drug delivery systems. Micelles (right) are composed of a solid lipid core with the polar heads exposed to the aqueous environment. Liposomes (left) are particles with a hpid bilayer surrounding an aqueous core. Drug can be encapsulated in the hydrophobic regions of the lipid particle, in the aqueous environment of the liposome, or adsorbed to the surface of the lipid particle. 

Monck, M.A., Mori, A., Lee, D., et al. (2000). Stabilized plasmid-lipid particles Pharmacokinetics and plasmid delivery to distal tumors following intravenous injection. J. Dnug Tanget, 7, 439 152. 

Figure 8-12 (A) 31P NMR spectra of different phospholipid phases. Hydrated soya phosphatidylethanolamine adopts the hexagonal Hn phase at 30°C. In the presence of 50 mol% of egg phosphatidylcholine only the bilayer phase is observed. At intermediate (30%) phosphatidylcholine concentrations an isotropic component appears in the spectrum. (B) Inverted micelles proposed to explain "lipidic particles" seen in freeze fracture micrographs of bilayer mixture of phospholipids, e.g., of phosphatidylethanolanine + phosphatidylcholine + cholesterol. From de Kruijft et al.m Courtesy of B. de Kruijft.

A third important structural pattern involves extensive use of amphipathic helices that lie partially embedded in a membrane surface. For example, the blood lipoproteins are lipid particles partially coated by amphipathic helices (Chapter 21).200 201... 

In addition, to release lipids from source material, such as those in starch, fish meal, or milk, it might be necessary to treat the sample with an acid prior to lipid extraction (see Basic Protocol 4). In the case of milk, addition of ammonium hydroxide is necessary to dissolve casein prior to lipid extraction, which will release the lipids from its surrounding matrix (e.g., from the film surrounding the fat globules in milk). Furthermore, in certain cases, it is necessary to predry the sample in order to allow efficient and complete extraction of lipids. Particle size reduction is another factor that may improve lipid extraction efficacy. 

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