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. After extrusion, liposomes were desalted in hbse buffer by chromatography on sepharose cl4b, loaded with doxorubicin hcl 50200 mgyml, 98% pure. Preparation and characterization of doxorubicinloaded.
Pharmacokinetics of pegylated liposome doxorubicin. 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. Classification, preparation, and applications article pdf available in nanoscale research letters 81. Characterization of sterically stabilized cisplatin liposomes.
Doxorubicin entrapped in sterically stabili zed liposomes. Improved liposome stability and drug retention significantly. Improvements in pharmacokinetics and antitumor therapeutic efficacy article pdf available in proceedings of the national academy of sciences 8824. The aim of the present study is to investigate the vitamin b12 conjugated doxorubicin loaded sterically stabilized liposomes for tumor targeting. In this study, we aimed at the wnt signaling characteristic of cscs and designed a liposomal drug delivery system to target cscs. Using synchrotron smallangle xray scattering, we were able to characterize the hydrophilic shell of the polyethylene glycol chains. 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. A growth factor antagonist as a targeting agent for sterically stabilized liposomes in human small cell lung cancer joao n. Doxorubicin encapsulated in stealth liposomes conferred. Preparation and characterization of doxorubicinloaded sterically.
Doxorubicin hydrochloride liposome injection is doxorubicin hydrochloride, an anthracycline topoisomerase inhibitor, that is encapsulated in pegylated liposomes for intravenous use. The purpose of this present study was to evaluate the antiangiogenic activity of sterically stabilized liposomes containing paclitaxel sslptx. Pdf the results obtained in this study establish that liposome formulations incorporating a synthetic polyethylene glycolderivatized. 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.
Liposomes containing colloidal gold are a useful probe of liposomecell interactions. We designed a novel doxorubicin dox sterically stabilized liposome system coloaded with the lowdose pgp inhibitor cyclosporine a. Antibodytargeted delivery of doxorubicin entrapped in. Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model. A closer look at the structure of sterically stabilized. To compare the performance of sterically stabilized, doxorubicinloaded liposomes with and without surface attached specific antibodies dssil a. Doxorubicin encapsulated in sterically stabilized liposomes is. Attachment of antibodies to sterically stabilized liposomes.
Previous studies performed in rats showed that doxorubicin containing liposomes can. 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. These new liposome formulations of vincristine and doxorubicin were significantly more effective than the free drugs in curing the mice. Doxorubicin encapsulated in sterically stabilized liposomes. Doxorubicin encapsulated in sterically stabilized liposomes for the. Doxorubicin liposomal fda prescribing information, side. 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. Sterically stabilized liposomes, containing entrapped doxorubicin, targeted to squamous cell. 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. Doxorubicin entrapped in sterically stabilized liposomes. Doxorubicin encapsulated in stealth liposomes conferred with.
Pdf huang s, stauffer p, hong k, guo j, phillips t, huang 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. Vcr and doxorubicin doxil in liposomes were compared, and the 2 preparations were also tested in alternate and in simultaneous combinations. Galactosylated liposomes for targeted codelivery of. Affibody molecules are small and stable antigenbinding molecules derived from the b domain of protein a. To prospectively evaluate the shortterm toxicoses associated with pegylatedliposomal doxorubicin doxil administered to dogs with measurable tumors of various histologic types and sites. A growth factor antagonist as a targeting agent for.
Antiangiogenic activity of sterically stabilized liposomes. 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. Liposomes are enclosed phospholipid vesicles that have been clinically approved to encapsulate a wide range of therapeutics and diagnostics bulbake et al. Alza corporation, mountain view, ca loaded in the aqueous phase of sterically stabilized 100 nm liposomes 15,16. Development and characterization of doxorubicin bearing.
The antitumor activity of a doxorubicin loaded, irgdmodified. Intracellular delivery of doxorubicin with rgdmodified sterically stabilized liposomes for an improved antitumor efficacy. However, they are usually difficult to be treated and notoriously resilient to drug eradication. The chemical name of doxorubicin hydrochloride is 8s,10s103amino2,3,6trideoxy.
C dox leakage from liposomes following the labeling incubation. Physicochemical properties of doxorubicin and sirna in sterically stabilized galactosylated liposomes. The codelivery of a lowdose pglycoprotein inhibitor with. 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. Pdf abstract the ability of pegylated liposomes sterically stabilized liposomesssl to. 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. Targeted treatment of choroidal neovascularization using. In this report we present several findings obtained with liposomes sterically stabilized by the peg headgroups of a synthetic phospholipid peg. Preliminary information regarding efficacy was also generated. Pdf sterically stabilized liposomes as a potent carrier for shikonin.
Microfluidics has been explored to prepare liposomes in a wellcontrolled, reproducible and highthroughput manner. We designed a novel doxorubicin dox sterically stabilized liposome system coloaded with the lowdose pgp inhibitor cyclosporine a csa doxcsassl. Formulation particle size nm zeta potential mv in water doxtoliposome ratio ww dox ee % galdoxl 98. Effects on bacterial blood clearance capacity of the mononuclear phagocyte system gert storm, marian t. This is the first demonstration of the therapeutic effectiveness of doxorubicin in sterically stabilized liposomes against human tumor xenografts. To compare the performance of sterically stabilized, doxorubicinloaded liposomes with and without surface attached specific antibodies dssil and dssl, respectively. Sterically stabilized liposomes containing doxorubi cin. Therapy of human ovarian carcinoma xenografts using. However, their circulation does significantly surpass that of free doxorubicin, resulting in tumor accumulation via the.
Intracellular delivery of doxorubicin with rgdmodified. Preclinical trial of doxorubicin entrapped in sterically. Inclusion of 2 molar % porphyrinphospholipid pop imparted optimal near infrared nir lighttriggered release of doxorubicin dox from conventional sterically stabilized stealth liposomes. Antibody targeting of doxorubicinloaded liposomes suppresses. These sterically stabilized liposomes stealth liposomes avoid rapid clearance by the reticuloendothelial system, thereby increasing their time in circulation 2, 3. In the study reported here, the human breastcancer cell line mcf7, chosen as a model of luminal a, was found to be lowpgp expressing.
Immunotargeting of liposomes to activated vascular. 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. 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. Sterically stabilized liposomes production using staggered. Download fulltext pdf download fulltext pdf liposome. Pharmacokinetics and tissue distribution of doxorubicin encapsulated in stable liposomes with long circulation times. 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.
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 effect of lyophilization on liposomal stability and hence expiration date were studied. We consider that such liposomes are sterically stabilized by the presence of the relevant headgroups on their surface 16. For more information fill in reader enquiry number 100 on the reader service card. Improved liposome stability and drug retention significantly increase the anticancer activity of encapsulated doxorubicin doxil, enhancing the effectiveness of chemotherapy and. Cdox, conventional liposomes containing doxorubicin. Llyxohexopyranosyloxy8glycolyl7,8,9,10tetrahydro6,8,11trihydroxy. Bakkerwoudenberg department of pharmaceutics, utrecht institute for pharmaceutical.
Pop liposomes and sterically stabilized liposomal dox ssld in 0. 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. Doxil sequus is a formulation of doxorubicin precipitated in sterically stabilized liposomes. Targeting doxorubicin encapsulated in stealth liposomes to. Physicochemical properties of doxorubicin and sirna in stericallystabilized galactosylatedliposomes. The release of paclitaxel from sslptx was analyzed using a dialysis method. 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. The evaluation of the radial electron density profile of a drug containing a sterically stabilized liposomal system is described.
We applied a bivalent, highaffinity epidermal growth factor receptor egfrspecific affibody molecule for the generation of targeted pegylated liposomes. Intrabilayer 64cu labeling of photoactivatable, doxorubicin. The antitumor activity of a doxorubicin loaded, irgdmodified stericallystabilized liposome on b16f10 melanoma cells. Stealth liposomes can be used to extend the blood circulation time of encapsulated therapeutics. Doxorubicin in sterically stabilized liposomes nature. Jul 15, 20 the antitumor activity of a doxorubicin loaded, irgdmodified sterically stabilized liposome on b16f10 melanoma cells. Read attachment of antibodies to sterically stabilized liposomes. Plain and sterically stabilized liposomes were prepared by modified ethanol injection method followed by remote loading of doxorubicin by ammonium sulphate gradient method. The use of liposomes as drug delivery systems is the most promising technique for targeting drug especially for anticancer therapy. In this study sterically stabilized liposomes was prepared from dppccholesterolpegpe encapsulated doxorubicin. Therapy of mouse mammary carcinomas with vincristine and. Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes.
Overview of comments received on pegylated liposomal. Targeting of epidermal growth factor receptor egfr. Moreover, the effect of diode laser on the drug released. A group of 51 dogs with histologically confirmed malignancies received a total of 103 doxil treatments given i. Liposomebased drug delivery in breast cancer treatment. These sterically stabilized affibody liposomes sal were produced by chemical coupling of the cysteinemodified affibody molecule to.
It proved to be applicable and successful for treatment of ehrlich solid tumors implanted in mice and eliminated toxic side effects of doxorubicin. Liposomal encapsulation can substantially affect a drugs functional properties relative to those of the unencapsulated drug. Increased tumor uptake and therapeutic efficacy of doxorubicin in sterically stabilized liposomes shi kun huang,2 paul it stauffer, keelung hong, john w. Doxil doxorubicin hcl liposome injection is doxorubicin hydrochloride hcl encapsulated in stealth liposomes for intravenous administration. However, their circulation does significantly surpass that of free doxorubicin, resulting in tumor accumulation via the enhanced permeability and retention effect. Phase i and pharmacokinetic study of a stable, polyethylene.
1260 268 710 326 1398 1471 235 1619 1402 1431 1482 631 941 1061 549 123 905 812 1640 137 557 514 482 767 819 1283 1074 1238 522 287 897 261 138