The chemical name of doxorubicin hydrochloride is 8s,10s103amino2,3,6trideoxy. Doxorubicin encapsulated in sterically stabilized liposomes exhibits renal and biliary clearance properties that are independent of valspodar psc 833 under conditions that significantly inhibit nonencapsulated drug excretion1 rajesh krishna,2 natashia. Pdf huang s, stauffer p, hong k, guo j, phillips t, huang a. Pdf the results obtained in this study establish that liposome formulations incorporating a synthetic polyethylene glycolderivatized.
Cancer stem cells csc that may account for only a small fraction of tumor mass were found to play crucial roles during tumor initiating, progression, and metastasis. They have been used successfully to deliver chemotherapeutic agents such as doxorubicin, epirubicin, and vincristine to mouse colon or mammary tumors and have been shown to. Antiangiogenic activity of sterically stabilized liposomes. Classification, preparation, and applications article pdf available in nanoscale research letters 81. These sterically stabilized liposomes stealth liposomes avoid rapid clearance by the reticuloendothelial system, thereby increasing their time in circulation 2, 3. Pharmacokinetics and tissue distribution of doxorubicin encapsulated in stable liposomes with long circulation times. The antitumor activity of a doxorubicin loaded, irgdmodified stericallystabilized liposome on b16f10 melanoma cells. Targeting doxorubicin encapsulated in stealth liposomes to. Interest in liposomes as drug carriers was rejuvenated by the introduction of new ideas from membrane biophysics, and this multidisciplinary approach has enhanced prospects for their use in medicine 25. Doxil doxorubicin hcl liposome injection is doxorubicin hydrochloride hcl encapsulated in stealth liposomes for intravenous administration. Antibody targeting of doxorubicinloaded liposomes suppresses. Liposomal encapsulation can substantially affect a drugs functional properties relative to those of the unencapsulated drug. Affibody molecules are small and stable antigenbinding molecules derived from the b domain of protein a.
A group of 51 dogs with histologically confirmed malignancies received a total of 103 doxil treatments given i. Targeted treatment of choroidal neovascularization using. Microfluidics has been explored to prepare liposomes in a wellcontrolled, reproducible and highthroughput manner. These new liposome formulations of vincristine and doxorubicin were significantly more effective than the free drugs in curing the mice. Download fulltext pdf download fulltext pdf liposome. To compare the performance of sterically stabilized, doxorubicinloaded liposomes with and without surface attached specific antibodies dssil a.
For more information fill in reader enquiry number 100 on the reader service card. Llyxohexopyranosyloxy8glycolyl7,8,9,10tetrahydro6,8,11trihydroxy. C dox leakage from liposomes following the labeling incubation. Antibodytargeted delivery of doxorubicin entrapped in. Improved liposome stability and drug retention significantly increase the anticancer activity of encapsulated doxorubicin doxil, enhancing the effectiveness of chemotherapy and. Using synchrotron smallangle xray scattering, we were able to characterize the hydrophilic shell of the polyethylene glycol chains. Previous studies performed in rats showed that doxorubicin containing liposomes can. Doxorubicin encapsulated in stealth liposomes conferred with. A growth factor antagonist as a targeting agent for. Therapy of mouse mammary carcinomas with vincristine and. Alza corporation, mountain view, ca loaded in the aqueous phase of sterically stabilized 100 nm liposomes 15,16. Targeting of epidermal growth factor receptor egfr. Development and characterization of doxorubicin bearing. Improved liposome stability and drug retention significantly.
Inclusion of 2 molar % porphyrinphospholipid pop imparted optimal near infrared nir lighttriggered release of doxorubicin dox from conventional sterically stabilized stealth liposomes. Read attachment of antibodies to sterically stabilized liposomes. Intracellular delivery of doxorubicin with rgdmodified. However, they are usually difficult to be treated and notoriously resilient to drug eradication. Physicochemical properties of doxorubicin and sirna in stericallystabilized galactosylatedliposomes. Doxorubicin liposomal fda prescribing information, side. Sterically stabilized liposomes, containing entrapped doxorubicin, targeted to squamous cell. Effects on bacterial blood clearance capacity of the mononuclear phagocyte system gert storm, marian t. Doxorubicin encapsulated in sterically stabilized liposomes is. Stealth liposomes can be used to extend the blood circulation time of encapsulated therapeutics. Polyethylene glycol liposomes, containing entrapped doxorubicin, targeted to kln205 squamous cell carcinoma of the lung by means of specific antibodies attached at the liposome surface were capable of reducing tumor burden to a high degree and eradicating tumor in a significant percentage of mice. Intrabilayer 64cu labeling of photoactivatable, doxorubicin.
After extrusion, liposomes were desalted in hbse buffer by chromatography on sepharose cl4b, loaded with doxorubicin hcl 50200 mgyml, 98% pure. Phase i and pharmacokinetic study of a stable, polyethylene. Sep 29, 2004 read pharmacokinetics of sterically stabilized hexadecylphosphocholine liposomes versus conventional liposomes and free hexadecylphosphocholine in tumorfree and human breast carcinoma bearing mice, breast cancer research and treatment on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. The objective of this study was to develop an efficient vasculaturetargeted liposomal combretastatin a4 ca4, by the modification of the sterically stabilized liposomes ssl with a ligand of integrins and to explore the possibility of such system for the treatment of choroidal neovascularization cnv. This is the first demonstration of the therapeutic effectiveness of doxorubicin in sterically stabilized liposomes against human tumor xenografts.
Formulation particle size nm zeta potential mv in water doxtoliposome ratio ww dox ee % galdoxl 98. In this study sterically stabilized liposomes was prepared from dppccholesterolpegpe encapsulated doxorubicin. Pop liposomes and sterically stabilized liposomal dox ssld in 0. We consider that such liposomes are sterically stabilized by the presence of the relevant headgroups on their surface 16.
Improvements in pharmacokinetics and antitumor therapeutic efficacy article pdf available in proceedings of the national academy of sciences 8824. Development of antiproliferative longcirculating liposomes coencapsulating doxorubicin and curcumin, through the use of a qualitybydesign approach targeting doxorubicin encapsulated in stealth liposomes to solid tumors by non thermal diode laser. We applied a bivalent, highaffinity epidermal growth factor receptor egfrspecific affibody molecule for the generation of targeted pegylated liposomes. Pharmacokinetics of pegylated liposome doxorubicin. Doxorubicin encapsulated in sterically stabilized liposomes for the. Read pharmacokinetics of sterically stabilized hexadecylphosphocholine liposomes versus conventional liposomes and free hexadecylphosphocholine in tumorfree and human breast carcinoma bearing mice, breast cancer research and treatment on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Therapy of human ovarian carcinoma xenografts using. The aim of the present study is to investigate the vitamin b12 conjugated doxorubicin loaded sterically stabilized liposomes for tumor targeting. The use of liposomes as drug delivery systems is the most promising technique for targeting drug especially for anticancer therapy. Sterically stabilized liposomes production using staggered. Characterization of sterically stabilized cisplatin liposomes.
The codelivery of a lowdose pglycoprotein inhibitor with. These sterically stabilized affibody liposomes sal were produced by chemical coupling of the cysteinemodified affibody molecule to. Overview of comments received on pegylated liposomal. A growth factor antagonist as a targeting agent for sterically stabilized liposomes in human small cell lung cancer joao n. In this study, we aimed at the wnt signaling characteristic of cscs and designed a liposomal drug delivery system to target cscs. To compare the performance of sterically stabilized, doxorubicinloaded liposomes with and without surface attached specific antibodies dssil and dssl, respectively. Bakkerwoudenberg department of pharmaceutics, utrecht institute for pharmaceutical. Preparation and characterization of doxorubicinloaded. Preliminary information regarding efficacy was also generated. Doxorubicin encapsulated in sterically stabilized liposomes. Galactosylated liposomes for targeted codelivery of.
Doxorubicin hydrochloride liposome injection is doxorubicin hydrochloride, an anthracycline topoisomerase inhibitor, that is encapsulated in pegylated liposomes for intravenous use. Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes. Antibodytargeted delivery of doxorubicin entrapped in sterically stabilized liposomes can eradicate lung cancer in mice1 imran ahmad, michael longenecker, john samuel, and theresa m. Increased tumor uptake and therapeutic efficacy of doxorubicin in sterically stabilized liposomes shi kun huang,2 paul it stauffer, keelung hong, john w. A closer look at the structure of sterically stabilized. In the study reported here, the human breastcancer cell line mcf7, chosen as a model of luminal a, was found to be lowpgp expressing. It proved to be applicable and successful for treatment of ehrlich solid tumors implanted in mice and eliminated toxic side effects of doxorubicin. Moreover, the effect of diode laser on the drug released.
Doxorubicin entrapped in sterically stabili zed liposomes. Pdf sterically stabilized liposomes as a potent carrier for shikonin. Sterically stabilized liposomes containing doxorubi cin. The antitumor activity of a doxorubicin loaded, irgdmodified. Doxorubicin in sterically stabilized liposomes nature. Cdox, conventional liposomes containing doxorubicin. Polymerbased anthracyclines have not achieved the same degree of prolonged circulation as sterically stabilized liposomal doxorubicin. Doxil sequus is a formulation of doxorubicin precipitated in sterically stabilized liposomes. Doxorubicin encapsulated in stealth liposomes conferred. Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model. Liposomes are enclosed phospholipid vesicles that have been clinically approved to encapsulate a wide range of therapeutics and diagnostics bulbake et al. Apr 27, 2001 although sterically stabilized liposomes are able to traverse the endothelium and to extravasate into the extracellular spaces, whether the presence of a large molecule like peg on the surface of the liposome may impede the tumor targeting efficiency is a major concern.
In this report we present several findings obtained with liposomes sterically stabilized by the peg headgroups of a synthetic phospholipid peg. Doxorubicin entrapped in sterically stabilized liposomes. Characterization of the peg layer of sterically stabilized liposomes. The evaluation of the radial electron density profile of a drug containing a sterically stabilized liposomal system is described. Pdf abstract the ability of pegylated liposomes sterically stabilized liposomesssl to. The release of paclitaxel from sslptx was analyzed using a dialysis method.
Attachment of antibodies to sterically stabilized liposomes. Physicochemical properties of doxorubicin and sirna in sterically stabilized galactosylated liposomes. However, their circulation does significantly surpass that of free doxorubicin, resulting in tumor accumulation via the. Plain and sterically stabilized liposomes were prepared by modified ethanol injection method followed by remote loading of doxorubicin by ammonium sulphate gradient method. Jul 15, 20 the antitumor activity of a doxorubicin loaded, irgdmodified sterically stabilized liposome on b16f10 melanoma cells. To prospectively evaluate the shortterm toxicoses associated with pegylatedliposomal doxorubicin doxil administered to dogs with measurable tumors of various histologic types and sites. Liposomes cannowbe designed rationally, resulting in nonreactive sterically stabilized liposomes sls, as well as polymorphic catonic. Vcr and doxorubicin doxil in liposomes were compared, and the 2 preparations were also tested in alternate and in simultaneous combinations. Intracellular delivery of doxorubicin with rgdmodified sterically stabilized liposomes for an improved antitumor efficacy.
Immunotargeting of liposomes to activated vascular. Antibodytargeted delivery of doxorubicin entrapped in sterically stabili zed liposomes can eradicate lung cancer in mice1 imran ahmad, michael longenecker, john samuel, and theresa m. Improved liposome stability and drug retention significantly increase the anticancer activity of encapsulated doxorubicin doxil, enhancing the effectiveness of chemotherapy and potentially reducing its toxicity. In clusion of 2 molar % porphyrinphospholipid pop imparted optimal near infrared nir lighttriggered release of doxorubicin dox from conventional sterically stabilized stealth liposomes. Preclinical trial of doxorubicin entrapped in sterically.
Liposomes containing colloidal gold are a useful probe of liposomecell interactions. The purpose of this present study was to evaluate the antiangiogenic activity of sterically stabilized liposomes containing paclitaxel sslptx. We designed a novel doxorubicin dox sterically stabilized liposome system coloaded with the lowdose pgp inhibitor cyclosporine a csa doxcsassl. The effect of lyophilization on liposomal stability and hence expiration date were studied. Liposomebased drug delivery in breast cancer treatment. However, their circulation does significantly surpass that of free doxorubicin, resulting in tumor accumulation via the enhanced permeability and retention effect. In vitro and in vivo author links open overlay panel xiaobing xiong 1 yue huang 2 wanliang lu 1 xuan zhang 1 hua zhang 1 tsuneji nagai 3 qiang zhang 1. Pdf huang s, stauffer p, hong k, guo j, phillips t. Two liposomal formulations have been approved by the us food and drug administration fda and are commercially available in the usa, europe and japan for the treatment of aidsrelated kaposis sarcoma. Indeed, the uptake of sterically stabilized liposomes in vitro by bone marrowderivedmurinemacrophages37 andbycv1cells, a primate cell line of epithelial origin 38, is significantly reduced comparedto conventional liposomes. Preparation and characterization of doxorubicinloaded sterically. We designed a novel doxorubicin dox sterically stabilized liposome system coloaded with the lowdose pgp inhibitor cyclosporine a. Doxorubicin encapsulated in sterically stabilized liposomes exhibits renal and biliary clearance properties that are independent of valspodar psc 833 under conditions that significantly inhibit nonencapsulated drug excretion1 rajesh krishna,2 natashia mcintosh, k.
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