Liposomal Blockade of the Reticuloendothelial System: Improved Tumor Imaging with Small Unilamellar Vesicles

Proffitt, Richard T.; Williams, Lawrence E.; Presant, Cary A.; Tin, George W.; Uliana, Joseph A.; Gamble, Ronald C.; Baldeschwieler, John D.

doi:10.1126/science.6836294

Cited by 177 publications

(61 citation statements)

References 21 publications

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“…9 A major limiting factor to the systemic use of particulate delivery systems is the rapid clearance of carrier from the blood circulation by reticuloendothelial system (RES). Various techniques such as suppression of RES 10 and modification of surface characteristics of drug carriers by coating with block copolymers 11 were attempted to reduce the RES uptake. The second approach has been shown to be highly effective in altering the biodistribution pattern of colloidal drug carriers.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Biodistribution Studies of Doxorubicin Loaded Poly(butyl Cyanoacrylate) Nanoparticles Synthesized by Two Different Techniques

Reddy¹,

Murthy²

2004

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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The aim of the study is to determine and compare the pharmacokinetics and tissue distribution of Doxorubicin (Dox) delivered as solution or through nanoparticles after intravenous (i.v.) and intraperitoneal (i.p.) injection. Doxorubicin loaded poly(butyl cyanoacrylate) nanoparticles were synthesized by dispersion polymerization (DP) and emulsion polymerization (EP) techniques. The drug loaded DP and EP nanoparticles were administered by i.v. or i.p. routes and the respective pharmacokinetics and tissue distribution were determined. Both types of nanoparticles significantly enhanced the elimination half-life (T 1/2 ), mean residence time (MRT) AUC [0][1][2][3][4][5][6][7][8] , AUC 0-∞ and AUMC 0-8 of Dox in blood after i.v. injection. Dox delivered through DP nanoparticles rapidly disappeared from blood and distributed to the organs of reticuloendothelial system (RES). But, the clearance of Dox delivered through EP nanoparticles from blood was slower than this of the DP nanoparticles and Dox solution. After i.p. injection, the Dox loaded into DP nanoparticles quickly appeared in blood and undergone rapid distribution to the organs of RES, while the Dox loaded into EP nanoparticles absorbed slowly into blood and remained in the circulation for longer time. The absorption into blood of Dox delivered through DP and EP nanoparticles after i.p. injection was relatively rapid and higher than Dox solution. The T 1/2 , MRT, AUC [0][1][2][3][4][5][6][7][8] , AUC 0-∞ and AUMC 0-8 of Dox in blood were significantly higher and the clearance (Cl) was lower than for the Dox solution after i.p. injection. The tissue concentrations of Dox delivered through nanoparticles after i.p. injection were significantly lower than after i.v. injection. The bioavailability (F) of Dox was greatly enhanced by DP (∼1.9 fold) and EP nanoparticles (∼2.12 fold) compared to Dox solution after i.p. injection. EP nanoparticles significantly enhanced the bioavailability, MRT, T 1/2 , AUC 0-8 , AUC 0-∞ and AUMC 0-8 of Dox than DP nanoparticles. This signifies the advantage of EP nanoparticles in increasing the elimination half-life of Dox both after i.v. and i.p. injection and enhanced bioavailability after i.p. injection, which is expected to improve the therapeutic efficacy of Dox and reduce the Dox-associated systemic toxicity. Importantly, both DP and EP nanoparticles greatly reduced the distribution of Dox to heart both after i.v. and i.p. injection, suggesting their potential in reducing Dox-associated cardiotoxicity.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Biodistribution Studies of Doxorubicin Loaded Poly(butyl Cyanoacrylate) Nanoparticles Synthesized by Two Different Techniques

Reddy¹,

Murthy²

2004

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…It is now generally recognized that preferential delivery of anticancer drugs to tumor sites following intravenous injection can be achieved by encapsulation of these drugs in large unilamellar vesicles (LUVs) exhibiting a small size (Ͻ100 nm diameter) and extended circulation lifetimes (circulation half-life in mice Ͼ5 h). [7][8][9] The accumulation of these drug delivery systems at disease sites, which includes sites of infection and inflammation as well as tumors, has been attributed to enhanced permeability of the local vasculature in diseased tissue. 10 A gene delivery system containing an encapsulated plasmid for systemic applications should therefore be small (Ͻ100 nm diameter) and must exhibit extended circulation life-times to achieve enhanced delivery to disease sites.…”

Section: Introductionmentioning

confidence: 99%

Stabilized plasmid-lipid particles: construction and characterization

et al. 1999

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A detergent dialysis procedure is described which allows of up to 70% and permits inclusion of 'fusigenic' lipids such encapsulation of plasmid DNA within a lipid envelope, as dioleoylphosphatidylethanolamine (DOPE). The in vitro where the resulting particle is stabilized in aqueous media transfection capabilities of SPLP are demonstrated to be by the presence of a poly(ethyleneglycol) (PEG) coating. strongly dependent on the length of the acyl chain conThese 'stabilized plasmid-lipid particles' (SPLP) exhibit an tained in the ceramide group used to anchor the PEG polyaverage size of 70 nm in diameter, contain one plasmid mer to the surface of the SPLP. Shorter acyl chain lengths per particle and fully protect the encapsulated plasmid from result in a PEG coating which can dissociate from the digestion by serum nucleases and E. coli DNase I. Encap-SPLP surface, transforming the SPLP from a stable parsulation is a sensitive function of cationic lipid content, with ticle to a transfection-competent entity. It is suggested that maximum entrapment observed at dioleoyldimethylam-SPLP may have utility as systemic gene delivery systems monium chloride (DODAC) contents of 5 to 10 mol%. The for gene therapy protocols. formulation process results in plasmid-trapping efficiencies

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“…у5 h in murine models) liposomes results in preferential delivery of encapsulated drug to distal tumors due to increased vascular permeability in these regions. [9][10][11] It therefore follows that intravenous injection of plasmid DNA encapsulated in small, long circulating lipid particles should give rise to preferential delivery of plasmid DNA to tumor sites. Recent work has shown that plasmid DNA can be encapsulated in small (approximately 70 nm diameter) 'stabilized plasmid-lipid particles' (SPLP) that contain one plasmid per particle.…”

Section: Introductionmentioning

confidence: 99%

Stabilized plasmid-lipid particles for systemic gene therapy

et al. 2000

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The structure of 'stabilized plasmid-lipid particles' (SPLP) and their properties as systemic gene therapy vectors has been investigated. We show that SPLP can be visualized employing cryo-electron microscopy to be homogeneous particles of diameter 72 ± 5 nm consisting of a lipid bilayer surrounding a core of plasmid DNA. It is also shown that SPLP exhibit long circulation lifetimes (circulation half-life Ͼ6 h) following intravenous (i.v.) injection in a murine tumor model resulting in accumulation of up to 3% of the total injected dose and concomitant reporter gene expression at a distal (hind flank) tumor site. In contrast, i.v. injection of

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Liposomal Blockade of the Reticuloendothelial System: Improved Tumor Imaging with Small Unilamellar Vesicles

Cited by 177 publications

References 21 publications

Pharmacokinetics and Biodistribution Studies of Doxorubicin Loaded Poly(butyl Cyanoacrylate) Nanoparticles Synthesized by Two Different Techniques

Pharmacokinetics and Biodistribution Studies of Doxorubicin Loaded Poly(butyl Cyanoacrylate) Nanoparticles Synthesized by Two Different Techniques

Stabilized plasmid-lipid particles: construction and characterization

Stabilized plasmid-lipid particles for systemic gene therapy

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