Browsing by Author "Si-Shen Feng"

Now showing 1 - 11 of 11

Development of docetaxel-loaded vitamin e TPGS micelles: Formulation optimization, effects on brain cancer cells and biodistribution in rats
(2012) Madaswamy S. Muthu; Sneha Avinash Kulkarni; Yutao Liu; Si-Shen Feng
Aim: This work aimed to develop docetaxel-loaded D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for brain cancer chemotherapy by taking advantage of polyethylene glycol for its long half-life in circulation and vitamin E for its high cellular uptake. Material and methods: TPGS micelles containing docetaxel or coumarin-6 were prepared by the solvent casting method and the direct dissolution method at high, moderate and low drug-loading levels. Results and discussion: The particle size of the docetaxel-loaded TPGS micelles ranged between 12 and 14 nm. Docetaxel formulated in the TPGS micelles of high, moderate and low drug-loading levels achieved lower IC 50 values compared with Taxotere® after 24-h incubation with C6 glioma brain cancer cells. The TPGS has much lower critical micelle concentration than most phospholipids in micellar formulation, which can be an efficient drug carrier across the blood brain-barrier with high drug encapsulation efficiency, cell uptake, cytotoxicity and desired biodistribution of the formulated drug. © 2012 Future Medicine Ltd.
In vivo and ex vivo proofs of concept that cetuximab conjugated vitamin E TPGS micelles increases efficacy of delivered docetaxel against triple negative breast cancer
(Elsevier Ltd, 2015) Rajaletchumy Veloo Kutty; Sing Ling Chia; Magdiel I. Setyawati; Madaswamy S. Muthu; Si-Shen Feng; David Tai Leong
In this study we examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. Here, we developed docetaxel-loaded vitamin E D-α-tocopheryl polyethylene glycol succinate (TPGS) micelles, of which the surface modified with cetuximab ligands for targeting epidermal growth factor receptors (EGFR) that are overexpressed in MDA-MB-231 breast cancer cells. The targeting micelles accumulated in the tumours immediately after the intravenous injection and retained for at least 24 h. The successful delivery of docetaxel into the tumours by the targeting micelles was shown by the greater degree of tumour growth inhibition than that for Taxotere® after the 15-day treatment. Furthermore, the explanted tumour culture study involving gene analysis and immunohistochemistry staining indicated that the in vivo micelle treatment induced cell cycle arrest and attenuated cell proliferation. In addition, the targeting and non-targeting micellar formulations brought about anti-angiogenesis and anti-migration effects. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGFR-overexpressing MDA-MB-231 tumours. © 2015 Elsevier Ltd.
Nanotheranostics - application and further development of nanomedicine strategies for advanced theranostics
(Ivyspring International Publisher, 2014) Madaswamy S. Muthu; David Tai Leong; Lin Mei; Si-Shen Feng
Nanotheranostics is to apply and further develop nanomedicine strategies for advanced theranostics. This review summarizes the various nanocarriers developed so far in the literature for nanotheranostics, which include polymer conjugations, dendrimers, micelles, liposomes, metal and inorganic nanoparticles, carbon nanotubes, and nanoparticles of biodegradable polymers for sustained, controlled and targeted co-delivery of diagnostic and therapeutic agents for better theranostic effects with fewer side effects. The theranostic nanomedicine can achieve systemic circulation, evade host defenses and deliver the drug and diagnostic agents at the targeted site to diagnose and treat the disease at cellular and molecular level. The therapeutic and diagnostic agents are formulated in nanomedicine as a single theranostic platform, which can then be further conjugated to biological ligand for targeting. Nanotheranostics can also promote stimuli- responsive release, synergetic and combinatory therapy, siRNA co-delivery, multimodality therapies, oral delivery, delivery across the blood-brain barrier as well as escape from intracellular autophagy. The fruition of nanotheranostics will be able to provide personalized therapy with bright prognosis, which makes even the fatal diseases curable or at least treatable at the earliest stage. © Ivyspring International Publisher.
Nanotheranostics: Advanced nanomedicine for the integration of diagnosis and therapy
(Future Medicine Ltd., 2014) Madaswamy S. Muthu; Lin Mei; Si-Shen Feng
[No abstract available]
Pharmaceutical stability aspects of nanomedicines
(2009) Madaswamy S. Muthu; Si-Shen Feng
[No abstract available]
Targeted nanomedicine for detection and treatment of circulating tumor cells
(2011) Madaswamy S. Muthu; Si-Shen Feng
[No abstract available]
Theranostic liposomes for cancer diagnosis and treatment: Current development and pre-clinical success
(2013) Madaswamy S Muthu; Si-Shen Feng
Liposomes are one of the effective drug delivery systems that are developed based on the nanotechnology concept. Liposomal formulation is the first nanomedicine approved by the US FDA for clinical application. Recently, the marketed liposomes and stealth liposomes have made impact for cancer therapy. In addition, a few receptor-targeted liposome products have been in different phases of clinical trials, which are yet to be marketed. In the present editorial, the advantages of vitamin E TPGS-coated liposomes over the currently available PEG-coated liposomes will be described and their great potentials for nanotheranostics for cancer imaging and therapy will be covered. © 2013 Informa UK, Ltd.
Theranostic liposomes of TPGS coating for targeted co-delivery of docetaxel and quantum dots
(2012) Madaswamy S. Muthu; Sneha A. Kulkarni; Anandhkumar Raju; Si-Shen Feng
The aim of this work was to develop a new type of d-alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) coated multi-functional (theranostic) liposomes, which contain both docetaxel and quantum dots (QDs) for cancer imaging and therapy. Non-targeting and folate receptor targeting TPGS coated theranostic liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta potential, surface chemistry and drug encapsulation efficiency. MCF-7 breast cancer cells of folate receptor overexpression were employed as an in vitro model to assess cellular uptake and cytotoxicity of the drug and QDs loaded liposomes. The mean particle size of the non-targeting and the targeting liposomes was found to be 202 and 210 nm, respectively. High resolution field emission transmission electron microscopy (FETEM) confirmed the presence of quantum dots in the peripheral hydrophobic membranes of the liposomes. The qualitative internalization of multi-functional liposomes by MCF-7 cells was visualized by confocal laser scanning microscopy (CLSM). The IC50 value, which is the drug concentration needed to kill 50% cells in a designated time period, was found to be 9.54 ± 0.76, 1.56 ± 0.19 and 0.23 ± 0.05 μg/ml for the commercial Taxotere ®, non-targeting and targeting liposomes, respectively after 24 h culture with MCF-7 cells. The targeting multi-functional liposomes showed greater efficacy than the non-targeting liposomes and thus great potential to improve the cancer imaging and therapy. © 2012 Elsevier Ltd.
Theranostic vitamin E TPGS micelles of transferrin conjugation for targeted co-delivery of docetaxel and ultra bright gold nanoclusters
(Elsevier Ltd, 2015) Madaswamy S. Muthu; Rajaletchumy Veloo Kutty; Zhentao Luo; Jianping Xie; Si-Shen Feng
The aim of this work was to develop an advanced theranostic micelles of D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), which are conjugated with transferrin for targeted co-delivery of docetaxel (DTX) as a model drug and ultra bright gold clusters (AuNC) as a model imaging agent for simultaneous cancer imaging and therapy. The theranostic micelles with and without transferrin conjugation were prepared by the solvent casting method and characterized for their particle size, polydispersity, surface chemistry, drug encapsulation efficiency, drug loading and cellular uptake efficiency. Transferrin receptors expressing MDA-MB-231-luc breast cancer cells and NIH-3T3 fibroblast cells (control cells without transferrin receptor expression) were employed as an invitro model to access cytotoxicity of the formulations. The overexpression of transferrin receptor on the surface of MDA-MB-231-luc cells was confirmed by flow cytometry. The biodistribution study and theranostic efficacy of the micelles were investigated by using the Xenogen IVIS® Spectrum imaging system, which includes AuNC based fluorescence imaging and luciferase induced bioluminescence imaging on MDA-MB-231-luc tumor bearing SCID mice. The IC50 values demonstrated that the non-targeted and targeted micelles could be 15.31 and 71.73 folds more effective than Taxotere® after 24h treatment with the MDA-MB-231-luc cells. Transferrin receptor targeted delivery of such micelles was imaged in xenograft model and showed their great advantages for real-time tumor imaging and inhibition of tumor growth. © 2014 Elsevier Ltd.
Trastuzumab-conjugated vitamin e TPGS liposomes for sustained and targeted delivery of docetaxel
(2013) Anandhkumar Raju; Madaswamy S Muthu; Si-Shen Feng
Objectives: In this study, the authors developed d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) liposomes and further conjugated them to trastuzumab for controlled and targeted delivery of docetaxel (DTX) as a model hydrophobic drug. Methods: DTX-or coumarin-6-loaded liposomes were prepared by solvent injection method and characterized for size and size distribution, surface charge, surface chemistry and drug encapsulation efficiency and drug release profile. SK-BR-3 cells were employed as an in vitro model for HER2-positive breast cancer and assessed for their cellular uptake and cytotoxicity of the two liposomal formulations. In vivo pharmacokinetics (PK) was investigated in Sprague-Dawley rats. Results: The IC50 value was found to be 20.23 ± 1.95, 3.74 ± 0.98, 0.08 ± 0.4 μg/ml for the marketed preparation of DTX, TPGS liposomes and trastuzumab-conjugated TPGS liposomes, respectively after 24 h incubation with SK-BR-3 cells. In vivo PK experiments showed that i.v. administration of trastuzumab-conjugated liposomes achieved 1.9 and 10 times longer half-life, respectively than PEG-coated liposomes and DTX. The area under the curve (AUC) was increased by 3.47-and 1.728-fold, respectively. Conclusion: The trastuzumab-conjugated vitamin E TPGS-coated liposomes showed greater potential for sustained and targeted chemotherapy in the treatment of HER2 overexpressing breast cancer. © 2013 Informa UK, Ltd.
Vitamin e TPGS coated liposomes enhanced cellular uptake and cytotoxicity of docetaxel in brain cancer cells
(2011) Madaswamy S. Muthu; Sneha A. Kulkarni; Jiaqing Xiong; Si-Shen Feng
The aim of this work was to develop a drug delivery system of liposomes, which are coated with d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), a PEGylated vitamin E, with docetaxel as a model drug for enhanced treatment of brain tumour in comparison with the nude liposomes as well as with the so-called stealth liposomes, i.e. those coated with polyethylene glycol (PEG), which have been intensive investigated in the literature. Docetaxel or coumarin-6 loaded liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta potential and drug encapsulation efficiency. C6 glioma cells were employed as an in vitro model to access cellular uptake and cytotoxicity of the drug or coumarin-6 loaded liposomes. The particle size of the PEG or TPGS coated liposomes was ranged between 126 and 191 nm. High-resolution field-emission transmission electron microscopy (FETEM) confirmed the coating of TPGS on the liposomes. The IC50 value, which is the drug concentration needed to kill 50% cells in a designated time period, was found to be 37.04 ± 1.05, 31.04 ± 0.75, 7.70 ± 0.22, and 5.93 ± 0.57 μg/ml for the commercial Taxotere ®, the nude, PEG coated and TPGS coated liposomes, respectively after 24 h culture with C6 glioma cells. The TPGS coated liposomes showed great advantages in vitro than the PEG coated liposomes. © 2011 Elsevier B.V. All rights reserved.