Long-circulating liposomes for drug delivery in cancer therapy: a review of biodistribution studies in tumor-bearing animals

Gabizón, Alberto; Goren, Dorit; Horowitz, Aviva T.; Tzemach, Dinah; Lossos, Alexander; Siegal, Tali

doi:10.1016/s0169-409x(96)00476-0

Cited by 192 publications

(123 citation statements)

References 19 publications

Supporting

Mentioning

118

Contrasting

Order By: Relevance

“…Because pharmacokinetic studies did not provide any evidence of significant drug release in plasma, in vivo prodrug activation and release must be a slow process occurring in tissues where long-circulating liposomes are mostly deposited. These tissues include tumor, liver, spleen, and skin (37). Indeed, our in vivo therapeutic studies show that PL-MLP has substantial antitumor activity (Figs.…”

Section: Discussionmentioning

confidence: 83%

“…In addition, delivery of lipophilic MMC prodrugs by means of liposomes or emulsions has also attempted in the past (45,46); however, to our knowledge, this is the first study combining a lipophilic prodrug with thiolytic release and a pegylated liposomal carrier that provides a clear advantage over earlier liposome formulations in terms of stability and circulation time. Although polymeric conjugates and liposomal formulations of cytotoxic drugs have seldom been compared head to head, one important difference lies in the fact that polymers usually release the drug after tumor cell uptake and breakdown in the endosomal compartment (33), whereas in the case of liposomes, especially for the pegylated ones, drug is released in the tumor extracellular fluid (32,37).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Reduced Toxicity and Superior Therapeutic Activity of a Mitomycin C Lipid-Based Prodrug Incorporated in Pegylated Liposomes

Gabizón

Tzemach

Horowitz³

et al. 2006

Clinical Cancer Research

Self Cite

114

View full text Add to dashboard Cite

Purpose: A lipid-based prodrug of mitomycin C [MMC; 2,3-(distearoyloxy)propane-1-dithio-4V-benzyloxycarbonyl-MMC] was designed for liposome formulation. The purpose of this study was to examine the in vitro cytotoxicity, pharmacokinetics, in vivo toxicity, and in vivo antitumor activity of this new lipid-based prodrug formulated in polyethylene glycol^coated (pegylated) liposomes. Experimental Design: MMC was released from the MMC lipid^based prodrug (MLP) by thiolytic-induced cleavage with a variety of thiol-containing reducing agents. MLP was incorporated with nearly 100% efficiency in cholesterol-free pegylated liposomes with hydrogenated phosphatidylcholine as the main component and a mean vesicle size of f90 nm.This formulation was used for in vitro and in vivo tests in rodents. Results: In vitro, the cytotoxic activity of pegylated liposomal MLP (PL-MLP) was drastically reduced compared with free MMC. However, in the presence of reducing agents, such as cysteine or N-acetyl-cysteine, its activity increased to nearly comparable levels to those of free MMC. Intravenous administration of PL-MLP in rats resulted in a slow clearance indicating stable prodrug retention in liposomes and long circulation time kinetics, with a pharmacokinetic profile substantially different from that of free MMC. In vivo, PL-MLP was f3-fold less toxic than free MMC.The therapeutic index and absolute antitumor efficacy of PL-MLP were superior to that of free MMC in the three tumor models tested. In addition, PL-MLP was significantly more active than a formulation of doxorubicin in pegylated liposomes (DOXIL) in the M109R tumor model, a mouse tumor cell line with a multidrug-resistant phenotype. Conclusions: Delivery of MLP in pegylated liposomes is a potential approach for effective treatment of multidrug-resistant tumors while significantly buffering the toxicity of MMC.

show abstract

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Reduced Toxicity and Superior Therapeutic Activity of a Mitomycin C Lipid-Based Prodrug Incorporated in Pegylated Liposomes

Gabizón

Tzemach

Horowitz³

et al. 2006

Clinical Cancer Research

Self Cite

114

View full text Add to dashboard Cite

show abstract

“…In addition, they are found in several industrial applications, e.g. as emulsifiers in pharmaceutical and food products and components of liposomes for cosmetics and drug delivery (Gabizon et al, 1997;Schneider, 2001).…”

Section: Introductionmentioning

confidence: 99%

Lipase-catalyzed interesterification of egg-yolk phosphatidylcholine and plant oils

Chojnacka¹,

Gładkowski²,

Kiełbowicz³

et al. 2014

Grasas y Aceites

View full text Add to dashboard Cite

SUMMARY:The incorporation of polyunsaturated fatty acids into the sn-1 position of egg-yolk phosphatidylcholine (PC) in the process of lipase-catalyzed interesterification was investigated. For this purpose plant oils containing these acids in the triacylglycerol (TAG) form were used as acyl donors and three commercially available immobilized lipases were examined as biocatalysts. In all the experiments the best results were obtained using Novozym 435. After 72 h of the reaction of PC with linseed oil the maximum incorporation of α-linolenic acid into PC was 34%. The result of this reaction was also a reduction in the n-6/n-3 ratio in egg-yolk PC from 24.5 to 0.7. The highest incorporation n-6 PUFAs into PC were obtained with evening primrose oil as the acyl donor, and in this case, 50.7% of n-6 PUFA as the sum of linoleic and γ-linolenic was achieved. The highest content of γ-linolenic acid in modified PC (7.3%) was achieved in the reaction of PC with borage oil. KEYWORDS:Egg-yolk phosphatidylcholine; Interesterification; Lipase; Plant oil; Polyunsaturated fatty acids; Structured phospholipids RESUMEN: Interesterificación de fosfatidilcolina de yema de huevo y aceites vegetales catalizada por lipasas. Se ha investigado la incorporación de ácidos grasos poliinsaturados en la posición sn-1 de fosfatidilcolina de yema de huevo (PC) en el proceso de interesterificación catalizado por lipasas. Para lograr este propósito, fueron examinados aceites vegetales que contienen estos ácidos en la forma de triacilgliceroles (TAG) como donadores de acilo y tres lipasas inmovilizadas disponibles comercialmente. En todos los experimentos los mejores resultados se obtuvieron para Novozym 435. La incorporación máxima de ácido α-linolénico en PC fue del 34% después de 72h de la reacción de PC con aceite de linaza. El resultado de esta reacción fue también la reducción de la relación de n-6/n-3 en PC de yema de huevo de 24.5 a 0.7. La incorporación más alta de n-6 PUFAs en PC se logró para el aceite de onagra como donador de acilo, en este caso se alcanzó el 50.7% de n-6 PUFA, como suma de los ácidos linoleico y γ-linolénico. El mayor contenido de ácido γ-linolénico en PC modificado (7.3%) se logró en la reacción de PC con aceite de borraja.

show abstract

“…PEG grafting has been shown to impart onto a large range of substrates improved properties, including reduced hemolytic toxicity, improved water solubility, and increased blood circulation times, (Medina and El-Sayed 2009;Middel et al 2002;Tekade et al 2009) and is advantageous in drugdelivery systems involving liposomes, nanoparticles, and peptides (Gabizon et al 1997;Kataoka et al 2001;Veronese 2001). PEGylated Si NPs with strong Si-C attachments have been prepared by Sudeep et al through the hydrosilation of H-terminated Si NP's with alkenyl-terminated PEGs (Sudeep et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Water-soluble PEGylated silicon nanoparticles and their assembly into swellable nanoparticle aggregates

Zhang

et al. 2015

J Nanopart Res

View full text Add to dashboard Cite

Water-soluble silicon nanoparticles were synthesized by grafting PEG polymers onto functionalized silicon nanoparticles with distal alkyne or azide moieties. The surface-functionalized silicon nanoparticles were produced in one step from the reactive high-energy ball milling (RHEBM) of silicon wafers with a mixture of either 5-chloro-1-pentyne in 1-pentyne or 1,7 octadiyne in 1-hexyne to afford air and water-stable chloroalkyl or alkynyl-terminated nanoparticles, respectively. Nanoparticles with the xchloroalkyl substituents were easily converted to xazidoalkyl groups through the reaction of the Si nanoparticles with sodium azide in DMF. The azidoterminated nanoparticles were then grafted with mono-alkynyl-PEG polymers using a coppercatalyzed alkyne-azide cycloaddition (CuAAC) reaction to afford core-shell silicon nanoparticles with a covalently attached PEG shell. Covalently linked Si nanoparticle clusters were synthesized via the CuAAC ''click'' reaction of functional Si NPs with a,xfunctional PEG polymers of various lengths. Dynamic light scattering studies show that the flexible globular nanoparticle aggregates undergo a solvent-dependent change in volume (ethanol [ dichloromethane [ toluene) similar in behavior to hydrogel nanocomposites.

show abstract

Long-circulating liposomes for drug delivery in cancer therapy: a review of biodistribution studies in tumor-bearing animals

Cited by 192 publications

References 19 publications

Reduced Toxicity and Superior Therapeutic Activity of a Mitomycin C Lipid-Based Prodrug Incorporated in Pegylated Liposomes

Reduced Toxicity and Superior Therapeutic Activity of a Mitomycin C Lipid-Based Prodrug Incorporated in Pegylated Liposomes

Lipase-catalyzed interesterification of egg-yolk phosphatidylcholine and plant oils

Water-soluble PEGylated silicon nanoparticles and their assembly into swellable nanoparticle aggregates

Contact Info

Product

Resources

About