The pharmacokinetics of 3H-Triamcinolone Acetonide-21-palmitate entrapped in liposomes with neutral, negative and positive surface charge was investigated in the male New Zealand White rabbit after a single intravenous bolus injection. Drug concentration-time data monitored in whole blood showed bi-exponential decay and were analysed by a least-squares regression analysis procedure to obtain pertinent pharmacokinetic parameters. The significance of the observed differences in the pharmacokinetics after administration of each type of liposome was assessed by the Analysis of Variance test method. Significant differences (p less than 0.05) were found in alpha, beta, (t 0.5)alpha, K12, and Vc. Positive liposomes apparently encountered a larger initial apparent volume of distribution than the neutral or negative type, and consequently exhibited demonstrably lower initial blood drug concentration, (Cb)0. Liposomes with different surface properties were removed from circulation at different rates and this resulted in significant difference (p less than 0.01) in the concentration of circulating liposomes an hour following injection of each type of liposome. A mean of 66 per cent of the initial concentration of positive liposomes remained in circulation an hour after injection whereas 11 and 23 per cent respectively of the neutral and negative type remained in circulation during the same time period. Liposomes with different surface properties apparently exhibited similar total body clearance of the encapsulated compound.

Animals↗

PubMedDate not supplied

Imaging liposomes at electron microscopic level: encapsulated colloidal iron as an electrondense marker for liposome-cell interactions.

Colloidal iron was encapsulated into liposomes prepared by different methods to provide an electrondense marker for easy identification of liposomes in cell and tissue culture. Stable colloidal iron solution can be prepared at virtually any concentration. The diameters of more than 75 per cent of the iron particles measured between 1 and 5 nm. Liposomes with a distinct electrondense core were evident at a colloidal iron solution concentration of 0.6 g/l. The colloidal iron labelled liposomes were easily identified in cells after incubation by routine electron microscopic procedures. Liposomes could be found in lysosomes or endosomes of human M21 melanoma cells. Intact, as well as partially degraded liposomes were present after two hours of incubation.

Capsules↗

PubMedDate not supplied

Liposomal pulmonary drug delivery. I. In vivo disposition of atropine base in solution and liposomal form following endotracheal instillation to the rabbit lung.

The potential of liposomes as carriers for local pulmonary drug delivery was investigated in the rabbit. Atropine base, a model compound for lipophilic drugs, was encapsulated in neutral MLVs and sprayed at the bifurcation of the trachea. Drug concentrations determined in the lung indicated liposomal encapsulation provided higher drug concentrations within pulmonary tissue for a more prolonged period of time as compared to the solution form. Comparison of drug levels in plasma and appearance of drug in urine demonstrated more rapid systemic absorption and elimination of 'free' drug. Greater accessibility of drug in solution to the systemic circulation was reflected in higher atropine concentrations in all internal organs studied. Liposome encapsulation favourably altered the disposition of atropine base when locally administered to the rabbit lung.

Animals↗

PubMedDate not supplied

Freeze substitution technique for identifying liposomes incorporated in emulsion and gel preparations.

The freeze-substitution technique was utilized for identifying unilamellar and multilamellar liposomes incorporated in gel or emulsion preparations. Samples of each preparation were rapidly frozen in liquid propane and the ice formed in the process was substituted with acetone containing 2 per cent osmium tetroxide at -70 degrees C. Electron micrographs obtained by both freeze-fracture and freeze-substitution methods showed the presence of either small unilamellar or multilamellar vesicles in all the liposome preparations. Results clearly demonstrated that freeze-substitution is a simple and cost-effective technique in comparison to the traditional freeze-fracture method and can be successfully used to characterize liposomes incorporated in dermatological or cosmetic vehicles.

Emulsions↗

PubMedDate not supplied

Dermal drug delivery by liposome encapsulation: clinical and electron microscopic studies.

The fate of liposomes and the encapsulated drug was studied after topical application on the skin. Lidocaine applied on the forearm of human volunteers produced greater local anaesthetic effect in the liposomal form than in the cream form (p less than or equal to 0.001 after 1 h application). Autoradiography demonstrated higher concentration (p less than or equal to 0.01) of 14C-lidocaine in the epidermis and dermis of guinea pigs treated with liposome-encapsulated lidocaine as opposed to lidocaine in Dermabase cream. Electron microscopic observations, using colloidal iron as an electrodense marker, indicated that intact liposomes penetrated into the skin and deposited in the dermis where they acted as a slow release depot system. On the basis of results in the human volunteers and animals, a hypothetical model for liposome-skin interaction is proposed.

Administration, Topical↗

PubMedDate not supplied

Liposomal drug delivery to the eye and lungs: a preliminary electron microscopy study.

Colloidal gold was used as an electron-dense marker for multilamellar vesicles to study the mechanism of liposome drug delivery to the eye and lung. A gold labelled multilamellar vesicle could be seen in the conjunctiva but there was no evidence of vesicles adsorbed to the epithelial surface of cornea or conjunctiva. In the lung, a free gold particle was isolated in type 1 epithelial cells and many vesicular structures were observed in the alveolar spaces which were not gold labelled. Experiments performed so far indicate that adsorption and not endocytosis was the major mechanism of uptake of drug or marker for multilamellar vesicles except for conjunctiva.

Adsorption↗