Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors

Williams, Joshua; Lansdown, Rachael; Sweitzer, Robert H.; Romanowski, Marek; LaBell, Rachel; Ramaswami, Rajan; Unger, Evan C.

doi:10.1016/s0168-3659(03)00241-4

Cited by 120 publications

(60 citation statements)

References 6 publications

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“…routes. There are several disadvantages to these methods; for example, oral administration of tablets or capsules could result in disorderly pharmocokinetics due to the exposure of these agents to the metabolic pathways of the body (4). This can result in larger than necessary doses being administered, which can further cause increased toxicity (5).…”

Section: Introductionmentioning

confidence: 99%

Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery

Sinha

Kim

Nie

et al. 2006

Molecular Cancer Therapeutics

713

437

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Nanotechnology refers to the interactions of cellular and molecular components and engineered materialstypically, clusters of atoms, molecules, and molecular fragments into incredibly small particles-between 1 and 100 nm. Nanometer-sized particles have novel optical, electronic, and structural properties that are not available either in individual molecules or bulk solids. The concept of nanoscale devices has led to the development of biodegradable self-assembled nanoparticles, which are being engineered for the targeted delivery of anticancer drugs and imaging contrast agents. Nanoconstructs such as these should serve as customizable, targeted drug delivery vehicles capable of ferrying large doses of chemotherapeutic agents or therapeutic genes into malignant cells while sparing healthy cells. Such ''smart'' multifunctional nanodevices hold out the possibility of radically changing the practice of oncology, allowing easy detection and then followed by effective targeted therapeutics at the earliest stages of the disease. In this article, we briefly discuss the use of bioconjugated nanoparticles for the delivery and targeting of anticancer drugs.

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Section: Introductionmentioning

confidence: 99%

Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery

Sinha

Kim

Nie

et al. 2006

Molecular Cancer Therapeutics

713

437

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“…The hydrophilic shell [usually a dense layer of polyethylene glycol (PEG) chains] evades the immune recognition 9,10 to have a long blood circulation time for passive accumulation into tumor tissues through their leaky blood capillaries, which is referred to as the enhanced permeability and retention effect. [9][10][11][12] The hydrophobic inner core can carry various anticancer drugs such as cisplatin, [13][14][15][16][17] doxorubicin, [18][19][20][21][22] paclitaxel, 23,24 camptothecin (CPT), 25,26 and etoposide. 27 The premature (within the first several hours) burst drug release of most of the carried drug, however, is a general problem of nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Multifunctioning pH‐responsive nanoparticles from hierarchical self‐assembly of polymer brush for cancer drug delivery

et al. 2008

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in Wiley InterScience (www.interscience.wiley.com).Polymer nanoparticles are extensively explored as drug carriers but they generally have issues of premature burst drug release, slow cellular uptake, and retention in acidic intracellular compartments. Herein, we report multifunctioning three-layered nanoparticles (3LNPs) that can overcome these problems. The 3LNPs have a poly(e-caprolactone) (PCL) core, a pH-responsive poly[2-(N,N-diethylamino)ethyl methacrylate](P-DEA) middle layer and a polyethylene glycol (PEG) outer layer. The pH-responsive PDEA layer is insoluble at pH above 7 but becomes positively charged and soluble via protonation at pH lower than 6.5. Thus, this layer has three functions: it covers on the PCL core inhibiting the premature burst drug release at the physiological pH, becomes positively charged and thus promotes endocytosis for fast cellular internalization in the acidic interstitium of solid tumors, and is highly positively charged in lysosomes to disrupt the lysosomal membrane and release the nanoparticle into the cytosol. The multifunctioning nanoparticles are an efficient carrier for cancer cytosolic drug delivery.

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“…The incorporation of 20-S-(+)-camptothecin (CPT) into liposomes is described in the literature mostly in a qualitative manner, 10 and the few quantitative data are difficult to compare because of the differences in their experimental approaches. [11][12][13] Many approaches [9][10][11][13][14][15] are aimed at incorporation of CPT or its derivatives into micellar, liposomal, or nanoparticular lipid carriers, separating free from incorporated CPT by various means. From our experience, the results of all these approaches may be hampered by incomplete separation of free and liposomal CPT.…”

Section: Introductionmentioning

confidence: 99%

A method to determine the incorporation capacity of camptothecin in liposomes

2004

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The purpose of this study was to establish a new experimental approach to determine the maximum amount of camptothecin (CPT) that can be incorporated in liposomes, and to use this method to compare the CPT-incorporation capacity of various liposome formulations. Small, CPT-saturated liposomes were prepared by dispersing freeze-dried blends of lipids and drug in phosphate buffer, and subsequent probe-sonication. Excess precipitated CPT could be separated from the liposomes by ultracentrifugation. The small and homogeneous liposome size obtained gave a good and reproducible recovery of liposomes in the supernatant (>80%), whereas the acidic pH (pH 6.0) kept CPT in its hydrophobic lactone form, which is poorly soluble in the buffer. The maximum CPT-incorporation capacity of 12 different liposome formulations was investigated, using the described method, and was found to vary widely. With liposomes made of neutral and anionic phospholipids, the solubility of CPT in the buffer was improved by approximately a factor of 10 (from ~2.7 to 15-50 µg/mL) as compared with buffer. With cationic liposomes containing 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), a maximum CPT-solubilization of ~100-fold, the buffer solubility was reached, probably owing to an electrostatic interaction between the cationic lipids and the carboxylate-CPT isomer. Increasing DOTAP fractions within egg-phosphatidylcholine (EPC)/DOTAP liposomes reached a CPT-incorporation plateau at ~20 mol% DOTAP. The presented approach appears suitable to study the incorporation capacity of any drug component within small vesicles as long as the liposome incorporation is high relative to the intrinsic water solubility of the drug.

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Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors

Cited by 120 publications

References 6 publications

Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery

Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery

Multifunctioning pH‐responsive nanoparticles from hierarchical self‐assembly of polymer brush for cancer drug delivery

A method to determine the incorporation capacity of camptothecin in liposomes

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