Design, synthesis and evaluation of N-acetyl glucosamine (NAG)–PEG–doxorubicin targeted conjugates for anticancer delivery

Pawar, Smita K.; Badhwar, Archana J.; Kharas, Firuza; Khandare, Jayant; Vavia, Pradeep R.

doi:10.1016/j.ijpharm.2012.05.078

Cited by 44 publications

(23 citation statements)

References 33 publications

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“…24 As a glucose receptor-targeting ligand, N-acetyl-d-glucosamine (NAG) is very innovative and promising. 25,26 Herein, NAG-NLCs were prepared using emulsification and solvent evaporation. 27 We showed the synthesis and characterization of PMAGP-GEM/PTX conjugates, and confirmed that the dual-drug conjugates in the NAG-NLCs (Scheme 1A) had controllable drug-to-drug molar ratios.…”

Section: Introductionmentioning

confidence: 99%

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer

Liang

Tian

et al. 2017

IJN

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Gemcitabine (GEM) and paclitaxel (PTX) are effective combination anticancer agents against non-small-cell lung cancer (NSCLC). At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic) and PTX (hydrophobic) into simplex tumor-targeted nanostructured lipid carriers (NLCs) for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N -acetyl- d -glucosamine (NAG) is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6- O -methacryloyl- d -galactopyranose)–GEM/PTX (PMAGP-GEM/PTX) conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1) exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor-targeted combination therapy to achieve maximal anticancer efficacy in NSCLC.

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Section: Introductionmentioning

confidence: 99%

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer

Liang

Tian

et al. 2017

IJN

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“…Therefore, DOX preferably induced the strong side-effect, although DOX disappears by a rapid opsonization and an up-take by the reticuloendothelial system (RES) of liver and spleen14, 15. To suppress the side-effect of DOX, a chemical conjugate of DOX was then investigated by using poly(ethylene glycol) to produce the prodrug16, or anti-body directed against the cancer cells17. Alternatively, the enhanced cytotoxicity of DOX could be achieved by a chemical conjugate with DNA18.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Cytotoxicity for Colon 26 Cells Using Doxorubicin-Loaded Sorbitan Monooleate (Span 80) Vesicles

Hayashi¹,

Tatsui

Shimanouchi

et al. 2013

Int. J. Biol. Sci.

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Span 80 (sorbitan monooleate) vesicles behaved differently from conventional phospholipid vesicles (liposomes) because the former had a more fluid interface. After doxorubicin hydrochloride (DOX) was encapsulated into the Span 80 vesicle (loading efficiency: 63 %), DOX-loaded Span 80 vesicles (DVs) were thereafter added to Colon 26 cells. It was suggested, from the flow cytometric analysis and confocal laser microscopic observation, that DVs directly deliver DOX into the cytoplasm of Colon 26 cells. DVs showed the different delivery manner from the DOX-loaded liposomes (DLs). It is considered that the difference of delivery manner between DVs and DLs resulted in the difference of cytotoxicity (IC50); i.e. IC50 values for DVs and DLs were 5 and > 30 μM, respectively. The results obtained herein would give the fundamental findings which can contribute to the improvement of formulation of conventional liposome-based carrier and its cytotoxicity.

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“…In this context, the objectives of designing polymeric nanopreparation is primarily driven to enhance the efficacy of the drug by (i) increasing the aqueous solubility (relevant for many drugs with low aqueous solubility), (ii) improving physiological stability against degrading enzymes or reducing the uptake by reticulo-endothelial system (RES) and (iii) targeting a drug to its specific site of action (in case of anticancer therapeutics -targeting to cancer cells). [38][39][40] Nanopreparations have immense potential in treating metastatic cancer with increased capacity to carry molecular payloads to the major sites of metastasis, e.g. lungs, liver and lymph nodes.…”

Section: Polymeric Nanopreparationsmentioning

confidence: 99%

Nanopreparations for Cancer Treatment and Diagnostics

Khandare¹,

Banerjee²,

Minko³

2014

Frontiers in Nanobiomedical Research

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A number of nanopreparations for cancer treatment have been recently developed. Several advantages of nanoscale-based cancer therapeutics determine a continuous interest to these preparations. Formulation of conventional anticancer drugs as nanopreparations substantially changes their properties and allows for improving their water solubility, stability, anticancer activity, pharmacokinetics and release profi le. It also permits the inclusion of several active components with different functionalities in one delivery system. Modern nanopreparations are capable of delivering hydro-and lipophilic anticancer drugs, nucleic acids, peptides, proteins and almost any other class of therapeutic agents. Such multicomponent multifunctional nanopreparations possess newly enhanced capabilities that exceed the potentials of each individual component applied separately. In addition to traditional chemotherapy, nanopreparations can be designed to be used in several other treatment protocols. They also can be employed as imaging agents to detect primary tumors and metastases. In addition, nanotechnology approach for anticancer formulations allows for the targeting of chemotherapeutic drugs and other active substances (nucleic acids, peptides, etc.) specifi cally to cancer cells therefore enhancing their anticancer activity and limiting severe adverse side effects upon healthy organs and tissues. The present work discusses examples of a few novel approaches to the formulations of nanopreparations for cancer treatment and imaging. Handbook of Nanobiomedical Research Downloaded from www.worldscientific.com by UNIVERSITY OF BIRMINGHAM LIBRARY -INFORMATION SERVICES on 03/22/15. For personal use only.

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Design, synthesis and evaluation of N-acetyl glucosamine (NAG)–PEG–doxorubicin targeted conjugates for anticancer delivery

Cited by 44 publications

References 33 publications

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer

Enhanced Cytotoxicity for Colon 26 Cells Using Doxorubicin-Loaded Sorbitan Monooleate (Span 80) Vesicles

Nanopreparations for Cancer Treatment and Diagnostics

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