ABSTRACT
This article presents an overview of the characteristics of liposomes as drug carriers, particularly in relation to liposomal formulations of amphotericin B. General features regarding structure, liposome-cell interactions, stability, encapsulation of active substances and elimination of liposomes are described. Up to the present time extensive efforts to produce similar or bioequivalent products of amphotericin B formulations, in particular in the case of liposomal amphotericin B, have been unsuccessful in spite of having a very similar composition and even an apparently identical manufacturing process. Guidelines for the development of generic liposomal formulations developed by the FDA and EMA are also summarized. Based on the available evidence of the composition of liposomes, any differences in the manufacturing process even if the same lipid composition is used may result in different final products. Therefore, it seems unreasonable to infer that all amphotericin B liposomal formulations are equal in efficacy and safety.
Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Amphotericin B/administration & dosage , Amphotericin B/adverse effects , Amphotericin B/pharmacokinetics , Animals , Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Antifungal Agents/pharmacokinetics , Chemistry, Pharmaceutical , Clinical Trials as Topic , Drug Carriers , Drug Compounding , Drug Evaluation, Preclinical , Humans , Liposomes/administration & dosage , Liposomes/chemistry , Liposomes/pharmacokinetics , Mycoses/drug therapy , Phospholipids/chemistry , Unilamellar Liposomes/pharmacokineticsABSTRACT
To prepare ethosome gel containing simvastatin ethosome and investigate the permeation behavior of simvastatin from ethosome gel. Cumulative permeation quantity in unit area and intradermal retention were the indicators to evaluate the effects of simvastatin in vitro percutaneous permeation behavior. Cumulative permeation quantity in unit area of simvastatin ethosome gel was significantly higher than other agents (P < 0.05), the intradermal retention of simvastatin ethosome gel, simvastatin gel containing 1%, and 3% menthol were significantly higher than simvastatin gel (P < 0.05). Ethosome gel could enhance the skin permeation and accumulation in a depot of simvastatin.
Subject(s)
Coronary Artery Disease/drug therapy , Gels/pharmacokinetics , Simvastatin/pharmacokinetics , Skin/metabolism , Unilamellar Liposomes/pharmacokinetics , Administration, Cutaneous , Animals , Drug Delivery Systems , Gels/chemistry , Gels/therapeutic use , Humans , In Vitro Techniques , Male , Mice , Mice, Inbred Strains , Simvastatin/chemistry , Simvastatin/therapeutic use , Unilamellar Liposomes/chemistry , Unilamellar Liposomes/therapeutic useABSTRACT
The aim of this study was to investigate the effect of liposomal membrane properties on cellular uptake and transcytosis across a tight Madin-Darby canine kidney (MDCK) cell barrier in vitro. More than 25 small vesicles were prepared by lipid film hydration/extrusion to generate small unilamellar vesicles. The fluorescence marker calcein was encapsulated to mimic hydrophilic drug transport. Marker uptake by MDCK cells seems to be mediated by different mechanisms for the liposomes used. It was mainly depending on membrane fluidity and vesicle charge. Liposomes L2 with a positive charge (325 +/- 3 pmol/well) and vesicles L3 containing the helper lipid dioleylphosphatidylethanolamine (DOPE) in their membrane (216 +/- 42 pmol/well) were taken up to the most. Selected liposomes were tested for their transcytotic transport across a MDCK monolayer. Liposomes L4 containing equimolar DOPE and octadecyl-1,1-dimethylpiperidin-1-ium-4-yl phosphate (OPP) were the most efficient vesicles for transcellular transport resulting in 808 +/- 30 pmol calcein/cm(2) in the basal medium (28.1% of total liposomal marker added). Transcytosis was positively correlated with membrane fluidity in the outer part of the bilayer, as electron paramagnetic resonance measurements revealed. We expect that an increase in membrane fluidity of vesicles should also improve the restricted transport of hydrophilic drugs across the blood-brain barrier.
Subject(s)
Drug Carriers/chemistry , Epithelial Cells/metabolism , Membrane Fluidity , Nanoparticles/chemistry , Unilamellar Liposomes/chemistry , Animals , Biological Transport , Cell Line , Cell Membrane/drug effects , Cell Membrane/metabolism , Dogs , Drug Carriers/pharmacokinetics , Drug Compounding , Electron Spin Resonance Spectroscopy , Epithelial Cells/drug effects , Fluoresceins/administration & dosage , Fluorescent Dyes/administration & dosage , Microscopy, Confocal , Microscopy, Fluorescence , Unilamellar Liposomes/pharmacokineticsABSTRACT
The (31)P NMR resonance from the inner and outer leaflets of DMPC in unilamellar vesicle bilayers has been split by use of the slowly penetrating paramagnetic shift reagent, Pr(3+). The perturbing effect of subsequently added iminosulfurane transdermal penetration enhancers (TPEs) is to accelerate the collapse of this splitting, especially in the case of the bromo derivative 3. The aforementioned acceleration of the splitting is enhanced by the addition of 16 mol% cholesterol. Conversely, 33 mol% cholesterol appears to seal the bilayer to the effect of the TPEs--even when present at 20 mol%. These observations are consistent with the deep penetration of the TPEs into the DMPC bilayer, i.e., the perturbation of the bilayer is transmembrane and supports a model in which a subset of the bromo TPE derivative 3 is kinetically trapped in the bilayer. This feature leads to an enhanced residence time of 3 in the bilayer, and by extension to the skin, and therefore to an explanation for the markedly enhanced activity of the bromo TPE derivative relative to that of other halogenated derivatives in the series of iminosulfuranes studied.
Subject(s)
Adjuvants, Pharmaceutic/chemistry , Models, Biological , Skin Absorption , Sulfur Compounds/chemistry , Unilamellar Liposomes/chemistry , Adjuvants, Pharmaceutic/pharmacokinetics , Anisotropy , Cholesterol/chemistry , Dimyristoylphosphatidylcholine/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Praseodymium/chemistry , Sulfur Compounds/pharmacokinetics , Unilamellar Liposomes/pharmacokineticsABSTRACT
This article illustrates some innovative applications of liposomes loaded with paramagnetic lanthanide-based complexes in MR molecular imaging field. When a relatively high amount of a Gd(III) chelate is encapsulated in the vesicle, the nanosystem can simultaneously affect both the longitudinal (R(1)) and the transverse (R(2)) relaxation rate of the bulk H2O H-atoms, and this finding can be exploited to design improved thermosensitive liposomes whose MRI response is not longer dependent on the concentration of the probe. The observation that the liposome compartmentalization of a paramagnetic Ln(III) complex induce a significant R(2) enhancement, primarily caused by magnetic susceptibility effects, prompted us to test the potential of such agents in cell-targeting MR experiments. The results obtained indicated that these nanoprobes may have a great potential for the MR visualization of cellular targets (like the glutamine membrane transporters) overexpressing in tumor cells. Liposomes loaded with paramagnetic complexes acting as NMR shift reagents have been recently proposed as highly sensitive CEST MRI agents. The main peculiarity of CEST probes is to allow the MR visualization of different agents present in the same region of interest, and this article provides an illustrative example of the in vivo potential of liposome-based CEST agents.
