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Showing papers by "Vinod Labhasetwar published in 2005"


Journal ArticleDOI
TL;DR: A novel water-dispersible oleic acid-Pluronic-coated iron oxide magnetic nanoparticle formulation that can be loaded easily with high doses of water-insoluble anticancer agents and demonstrated sustained intracellular drug retention relative to drug in solution and a dose-dependent antiproliferative effect in breast and prostate cancer cell lines.
Abstract: We have developed a novel water-dispersible oleic acid (OA)-Pluronic-coated iron oxide magnetic nanoparticle formulation that can be loaded easily with high doses of water-insoluble anticancer agents Drug partitions into the OA shell surrounding iron oxide nanoparticles, and the Pluronic that anchors at the OA−water interface confers aqueous dispersity to the formulation Neither the formulation components nor the drug loading affected the magnetic properties of the core iron oxide nanoparticles Sustained release of the incorporated drug is observed over 2 weeks under in vitro conditions The nanoparticles further demonstrated sustained intracellular drug retention relative to drug in solution and a dose-dependent antiproliferative effect in breast and prostate cancer cell lines This nanoparticle formulation can be used as a universal drug carrier system for systemic administration of water-insoluble drugs while simultaneously allowing magnetic targeting and/or imaging Keywords: Sustained release; wat

870 citations



Journal ArticleDOI
TL;DR: The increase in antiproliferative activity of the drug with incubation time in MCF-7/Adr cells with Tf-conjugated NPs suggests that the drug resistance can be overcome by sustaining intracellular drug retention.
Abstract: We studied the molecular mechanism of greater efficacy of paclitaxel-loaded nanoparticles (Tx-NPs) following conjugation to transferrin (Tf) ligand in breast cancer cell line. NPs were formulated using biodegradable polymer, poly(lactic-co-glycolide) (PLGA), with encapsulated Tx and conjugated to Tf ligand via an epoxy linker. Tf-conjugated NPs demonstrated greater and sustained antiproliferative activity of the drug in dose- and time-dependent studies compared to that with drug in solution or unconjugated NPs in MCF-7 and MCF-7/Adr cells. The mechanism of greater antiproliferative activity of the drug with conjugated NPs was determined to be due to their greater cellular uptake and reduced exocytosis compared to that of unconjugated NPs, thus leading to higher and sustained intracellular drug levels. The increase in antiproliferative activity of the drug with incubation time in MCF-7/Adr cells with Tf-conjugated NPs suggests that the drug resistance can be overcome by sustaining intracellular drug retention. The intracellular disposition characteristics of Tf-conjugated NPs following their cellular uptake via Tf receptors could have been different from that of unconjugated NPs via nonspecific endocytic pathway, thus influencing the NP uptake, their intracellular retention, and hence the therapeutic efficacy of the encapsulated drug.

340 citations


Journal ArticleDOI
TL;DR: The possibilities and challenges for targeted drug delivery in cancer therapy and better understanding of tumor biology in recent years provide optimism in developing successful cancer therapy.
Abstract: Chemotherapy has been the main modality of treatment for cancer patients; however, its success rate remains low, primarily due to limited accessibility of drugs to the tumor tissue, their intolerable toxicity, development of multi-drug resistance, and the dynamic heterogeneous biology of the growing tumors. Better understanding of tumor biology in recent years and new targeted drug delivery approaches that are being explored using different nanosystems and bioconjugates provide optimism in developing successful cancer therapy. This article reviews the possibilities and challenges for targeted drug delivery in cancer therapy.

273 citations


Journal ArticleDOI
TL;DR: Biodegradable porous polymeric microparticles with cancer cells grown into a tissue-like structure in vitro can be potentially used as a model system for preclinical evaluation of the cytotoxic effect of anticancer agents.

185 citations


Journal ArticleDOI
TL;DR: Understanding the molecular mechanisms that underlie the interactions of nanosystems with the cell, their uptake properties and retention will be crucial for the successful development of these systems.

129 citations


Journal ArticleDOI
TL;DR: In this article, the mean diameter of the iron-oxide nanoparticles was 9.3(±)0.8nm, and the saturation magnetization values measured at 10K varied from 66.1(± 0.7)emu∕g to 98.7(±0.5)mu ∕g.
Abstract: We have prepared and studied iron-oxide nanoparticles coated with oleic acid (OA) and Pluronic® polymer. The mean diameter of the iron-oxide nanoparticles was 9.3(±)0.8nm. Saturation magnetization values measured at 10K varied from 66.1(±0.7)emu∕gto98.7(±0.5)emu∕g. At 300K the loops showed negligible coercive field. The peaks in zero-field-cooled susceptibility decreased from 280to168K with increasing OA concentration up to 10.6wt%, and remained nearly constant for higher concentrations. This suggests that incomplete coverage of the OA allows small, interacting agglomerates to form.

74 citations


Patent
26 Sep 2005
TL;DR: In this paper, a magnetic nanoparticle composition with enhanced drug delivery characteristics is presented, which is composed of a magnetic particle core surrounded by a fatty acid and surfactant corona.
Abstract: The present invention is a magnetic nanoparticle composition with enhanced drug delivery characteristics. The magnetic nanoparticle composition is composed of a magnetic particle core surrounded by a fatty acid and surfactant corona. Methods for increasing the efficacy of therapeutic agents and facilitating diagnostic imaging are also provided.

48 citations


Patent
12 Dec 2005
TL;DR: In this paper, a composition composed of a therapeutic agent encapsulated in a copolymer of an N-alkylacrylamide, a vinyl monomer, and a polyethylene glycol (PEG) conjugate is presented.
Abstract: The present invention is a composition composed of a therapeutic agent encapsulated in a copolymer of an N-alkylacrylamide, a vinyl monomer, and a polyethylene glycol (PEG) conjugate and a method for using the same in the treatment or prevention of a disease or condition.

33 citations


Patent
09 May 2005
TL;DR: In this article, a transferrin-conjugated nanoparticle composition with sustained release characteristics was proposed for increasing the efficacy of therapeutic agents and a method for treating cancer using the transferrin con-guration.
Abstract: The present invention relates to a transferrin-conjugated nanoparticle composition with sustained release characteristics. A method for increasing the efficacy of therapeutic agents and a method for treating cancer using the transferrin-conjugated nanoparticle composition are also provided.

12 citations