Nanoparticles of Conjugated Methotrexate-Human Serum Albumin: Preparation and Cytotoxicity Evaluations

Taheri, Azade; Atyabi, Fatemeh; Nouri, Faranak Salman; Ahadi, Fatemeh; Derakhshan, Mohammad Ali; Amini, Mohsen; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Mansoori, Parvin; Dinarvand, Rassoul

doi:10.1155/2011/768201

Cited by 39 publications

(24 citation statements)

References 23 publications

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“…HSA has received special interest in drug delivery studies due to its ability for passive targeting through enhanced permeation and retention (EPR) effect which is related to both “enhanced permeation” of macromolecules through the fenestrated structure of tumor vasculature in addition to an “enhanced retention” which is considered to be related to the lack of effective lymphatic drainage in tumor tissues [6]. Furthermore it has been postulated that active targeting of HSA coated nanoparticles occurs through special albumin receptors on tumor cell membranes [7]. …”

Section: Introductionmentioning

confidence: 99%

Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

et al. 2013

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BackgroundPoly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues.MethodsPLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells.ResultsSize, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, −11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, −5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg).ConclusionIn conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may represent a promising drug delivery system in cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

et al. 2013

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“…Drugs can be incorporated within the HSA nanoparticles [27], or bound with covalent linkage to HSA [28,29]. The free amino groups of HSA could be used for covalent coupling of targeting moieties to the surface of the HSA nanoparticles [30–32].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

Taheri

Dinarvand

Atyabi

et al. 2011

IJMS

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Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX.

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“…34,35 Given the success of nab-paclitaxel, there has been a spurt in the research effort to develop albumin as a nanocarrier for many other drugs e.g. DTX, 36 doxorubicin, 37 gemcitabine,38 methotrexate,39 and noscapine. HPG NPs have, therefore, the potential to be drug carriers in a similar way, while being easier to produce as well as being a more versatile carrier for targeted drug delivery.…”

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confidence: 99%

Investigation of hydrophobically derivatized hyperbranched polyglycerol with PEGylated shell as a nanocarrier for systemic delivery of chemotherapeutics

Misri¹,

Wong²,

Shenoi

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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Nanoparticles of Conjugated Methotrexate-Human Serum Albumin: Preparation and Cytotoxicity Evaluations

Cited by 39 publications

References 23 publications

Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

Investigation of hydrophobically derivatized hyperbranched polyglycerol with PEGylated shell as a nanocarrier for systemic delivery of chemotherapeutics

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