Efficient targeting to alveolar macrophages by intratracheal administration of mannosylated liposomes in rats (original) (raw)
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Cancer research, 1985
The ability of a member of a new class of lipophilic muramyl dipeptide (MDP) derivative, muramyl dipeptide-glyceryldipalmitate (MDP-GDP), to induce alveolar macrophage cytotoxic activity in vitro towards B16 melanoma cells when incorporated into two types of liposome was studied. MDP-GDP incorporated into conventionally prepared liposomes formulated from distearoylphosphatidylcholine and phosphatidylserine (7:3 molar ratio) was 10-fold more effective than liposomes containing MDP, and 7000-fold more effective than free MDP in inducing macrophage cytotoxic activity. MDP-GDP incorporated into freeze-dried liposomes was 50,000- to 100,000-fold more effective than free MDP in inducing such activity. Freeze-dried liposomes containing MDP-GDP were efficiently localized in the lungs of normal mice, and induced cytotoxic activity in the alveolar macrophages. Such liposomes were able to significantly reduce the pulmonary metastatic burden of mice carrying the B16 melanoma. These data provide...
Cancer research, 1982
Functional and ultrastructural studies of liposomes injected i.v. into inbred C57BL/6N mice were performed to determine whether free liposomes can traverse capillaries. In the liver and spleen, organs with discontinuous (sinusoidal) capillaries, ultrastructural and cell fractionation studies revealed that small (300- to 800-A diameter), sonicated, unilamellar liposomes were more efficient in penetrating liver sinusoids to interact with hepatocytes than were large (0.5- to 10-micrometers) multilamellar liposomes. Ultrastructural studies of the behavior of liposomes in the continuous capillaries of the lungs revealed that circulating phagocytic cells engulf the liposomes in the capillaries. Transcapillary migration of free liposomes was not observed. We conclude that free liposomes are unable to extravasate to reach the alveoli for subsequent engulfment by alveolar macrophages. Instead, liposomes in the lung capillaries are engulfed by circulating blood phagocytes which subsequently m...
Targeted liposomal drug delivery to monocytes and macrophages
Journal of drug delivery, 2011
As the role of monocytes and macrophages in a range of diseases is better understood, strategies to target these cell types are of growing importance both scientifically and therapeutically. As particulate carriers, liposomes naturally target cells of the mononuclear phagocytic system (MPS), particularly macrophages. Loading drugs into liposomes can therefore offer an efficient means of drug targeting to MPS cells. Physicochemical properties including size, charge and lipid composition can have a very significant effect on the efficiency with which liposomes target MPS cells. MPS cells express a range of receptors including scavenger receptors, integrins, mannose receptors and Fc-receptors that can be targeted by the addition of ligands to liposome surfaces. These ligands include peptides, antibodies and lectins and have the advantages of increasing target specificity and avoiding the need for cationic lipids to trigger intracellular delivery. The goal for targeting monocytes/macrop...
Liposomes; from synthesis to targeting macrophages
Liposomes are a proposed tool to use for cell and tissue specific drug targeting. Because of their phospholipid membranes and carrying capacity within their spheres, liposomes are of particular interest for clinical applications. Stealth liposomes are especially important for these clinical applications because they are able to avoid the body's immune system. When it comes to synthesizing these liposomes, there are two major categories of synthesis techniques including active and passive loading. This paper focuses on passive loading techniques which involve mechanical dispersion methods, solvent dispersion methods, and detergent removal. Each of these categories of passive loading techniques has several methods for preparation, all of which aim at producing a homogeneous solution of liposomes with a high loading efficiency. Beyond preparation techniques, this paper also explores the use of liposomes in targeting macrophages to reduce inflammation in various diseases. From this, it has been found that liposomes are able to effectively target macrophages as well as deliver drugs to macrophages that cause the cells to reverse from a pro-inflammatory response to an anti-inflammatory response. These findings are critical as they may lead to further targeting of liposomes to specific cell types to treat other diseases in humans.