A novel method for measuring rigidity of submicron-size liposomes with atomic force microscopy

Nakano, Koji; Tozuka, Yuichi; Yamamoto, Hiromitsu; Kawashima, Yasunaru; Takeuchi, Hirofumi

doi:10.1016/j.ijpharm.2007.12.018

Cited by 64 publications

(49 citation statements)

References 16 publications

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“…Despite this, we found that this photobleaching approach could not be applied to the 400-and 650-nm vesicles, as their fluorescence intensity continued to increase for some time after landing, instead of following an exponential-like decay. Perhaps this is because these vesicles are much taller than the evanescent TIRF field, or perhaps an indication that these larger vesicles slowly become oblate as they adsorb onto the glass substrate, as shown by Nakano et al (32). Therefore, for the experiments involving different diameter vesicles, we then relied on our motor number estimates from these 200-nm vesicles (see below).…”

Section: Resultsmentioning

confidence: 99%

Motor coupling through lipid membranes enhances transport velocities for ensembles of myosin Va

Nelson

Trybus

Warshaw

2014

Proc. Natl. Acad. Sci. U.S.A.

100

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Myosin Va is an actin-based molecular motor responsible for transport and positioning of a wide array of intracellular cargoes. Although myosin Va motors have been well characterized at the single-molecule level, physiological transport is carried out by ensembles of motors. Studies that explore the behavior of ensembles of molecular motors have used nonphysiological cargoes such as DNA linkers or glass beads, which do not reproduce one key aspect of vesicular systems-the fluid intermotor coupling of biological lipid membranes. Using a system of defined synthetic lipid vesicles (100-to 650-nm diameter) composed of either 1,2-dioleoylsn-glycero-3-phosphocholine (DOPC) (fluid at room temperature) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) (gel at room temperature) with a range of surface densities of myosin Va motors (32-125 motors per μm 2 ), we demonstrate that the velocity of vesicle transport by ensembles of myosin Va is sensitive to properties of the cargo. Gel-state DPPC vesicles bound with multiple motors travel at velocities equal to or less than vesicles with a single myosin Va (∼450 nm/s), whereas surprisingly, ensembles of myosin Va are able to transport fluid-state DOPC vesicles at velocities significantly faster (>700 nm/s) than a single motor. To explain these data, we developed a Monte Carlo simulation that suggests that these reductions in velocity can be attributed to two distinct mechanisms of intermotor interference (i.e., load-dependent modulation of stepping kinetics and binding-site exclusion), whereas faster transport velocities are consistent with a model wherein the normal stepping behavior of the myosin is supplemented by the preferential detachment of the trailing motor from the actin track.liposome | actin filament M yosin Va is a processive, actin-based molecular motor critical for transport, morphology, and positioning of a wide variety of intracellular cargoes and organelles (1, 2). Although a single myosin Va can transport cargo in vitro, intracellular membrane-bound vesicular cargoes have a high surface density of motor proteins (3-5). Ensembles of motors that transport cargo in vitro have been shown to demonstrate enhanced run lengths (6-9) and slower movement, relative to the behavior of a single motor (6,(8)(9)(10)(11)(12)(13). Slower velocities are generally attributed to negative interference between motors that arise when rigidly coupled, high duty ratio motors step asynchronously (12). The stepping kinetics of myosin Va are load sensitive, whereby resistive loads slow the stepping rate, whereas assistive loads produce only a modest acceleration (14-16). This asymmetric load dependence causes an overall slowing for a motor ensemble. Indicative of the complexity of the intracellular environment, Efremov et al. (17) have shown that physiological vesicle transport (whether microtubule-or actin-based) does not directly mirror the behavior of the responsible molecular motor but is sensitive to aspects of the cargo itself. In some microtubule-based transport systems, v...

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Section: Resultsmentioning

confidence: 99%

Motor coupling through lipid membranes enhances transport velocities for ensembles of myosin Va

Nelson

Trybus

Warshaw

2014

Proc. Natl. Acad. Sci. U.S.A.

100

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“…It has been reported that particles smaller than 100 nm easily penetrate tumor tissues (Mayer et al, 1989). This is because these nano-particles can penetrate the discontinuous capillaries and fenestra of tumor tissues (Nakanoa et al, 2008). A size reduction step is occasionally incorporated into the niosome production procedure, subsequent to the initial hydration step.…”

Section: Niosome Size's Influence On In Vivo Performancementioning

confidence: 99%

Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations

2013

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Non-ionic surfactant vesicles, simply known as niosomes are synthetic vesicles with potential technological applications. Niosomes have the same potential advantages of phospholipid vesicles (liposomes) of being able to accommodate both water soluble and lipid soluble drug molecules control their release and as such serve as versatile drug delivery devices of numerous applications. Additionally, niosomes can be considered as more economically, chemically, and occasionally physically stable alternatives to liposomes. Niosomes can be fabricated using simple methods of preparations and from widely used surfactants in pharmaceutical technology. Many reports have discussed niosomes in terms of physicochemical properties and their applications as drug delivery systems. In this report, a brief and simplified summary of different theories of self-assembly will be given. Furthermore manufacturing methods, physical characterization techniques, bilayer membrane additives, unconventional niosomes (discomes, proniosomes, elastic and polyhedral niosomes), their recent applications as drug delivery systems, limitations and directions for future research will be discussed.

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“…This trend has already been reported by Utsumi et al 27 In addition, we previously reported that atomic force microscopy images showed that DSPC/SA/cholesterol liposomes changed from spheres to ovals on mica surfaces with an increase in cholesterol content, indicating the decrease of liposomal rigidity with an increase in cholesterol content. 28 The rigidity of DSPC/DCP/cholesterol liposomes may decrease with an increase in cholesterol content. We have reported that the efficiency of coumarin-6 delivery to the retina is higher for DSPC/ DCP/cholesterol liposomes than for EPC/DCP/cholesterol liposomes.…”

Section: Discussionmentioning

confidence: 99%

Physicochemical Properties Affecting Retinal Drug/Coumarin-6 Delivery from Nanocarrier Systems via Eyedrop Administration

Inokuchi¹,

Hironaka

Fujisawa

et al. 2010

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To elucidate the effect of physicochemical properties of nanocarrier systems on drug delivery efficiency to the retina by eyedrop administration in mice, rabbits, and monkeys. METHODS. Submicron-sized liposomes (ssLips) of different particle size, cholesterol content, surface charge, and multilamellar vesicles (MLV) were prepared by the hydration method. Fluorescence probe (coumarin-6)-incorporated liposomes, lipid emulsions, and FITC-labeled polystyrene particles were used to investigate their intraocular behavior after eyedrop administration, using epifluorescence microscopy in mice, rabbits, and monkeys. RESULTS. Delivery efficiency of fluorescent probes to the mouse retina from dropped liposomes was extensively improved by reducing their particle size (Ͻ600 nm) and cholesterol content, whereas negligible improvement was observed in the case of MLV. Furthermore, FITC-labeled polystyrene particles and coumarin-6 -incorporated lipid emulsions showed an insufficient effect on retinal delivery in mice even if their size was controlled at 110 nm. The highest accumulation of the fluorescent probe in the retina was observed around 30 minutes with any type of ssLip used, followed by the prompt disappearance of their fluorescence within 120 minutes in mice. Changes in the fluorescence intensity of coumarin-6 in rabbits and monkeys were observed in a manner similar to that described in mice. Retinal flat-mount images suggest that coumarin-6 incorporated in ssLip diffused from the iris and ciliary body side to the optic disc side in the retina after eyedrop administration. CONCLUSIONS. The delivery efficiency of coumarin-6 to the retina was altered depending on particle size, constituents, and rigidity. ssLips with appropriate features would be promising drug carriers for retinal delivery through eyedrops. (Invest Ophthalmol Vis Sci.

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A novel method for measuring rigidity of submicron-size liposomes with atomic force microscopy

Cited by 64 publications

References 16 publications

Motor coupling through lipid membranes enhances transport velocities for ensembles of myosin Va

Motor coupling through lipid membranes enhances transport velocities for ensembles of myosin Va

Recent advances in non-ionic surfactant vesicles (niosomes): self-assembly, fabrication, characterization, drug delivery applications and limitations

Physicochemical Properties Affecting Retinal Drug/Coumarin-6 Delivery from Nanocarrier Systems via Eyedrop Administration

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