- Enhanced noscapine delivery using estrogen-receptor-targeted nanoparticles for breast cancer therapy
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Noscapine (Nos), an orally available plant-derived antitussive alkaloid, is in phase II clinical trials for cancer chemotherapy. It has extensively been shown to inhibit tumor growth in nude mice bearing human xenografts of hematopoietic, breast, lung, ovarian, brain, and prostate origin. However, high tumor-suppressive Nos dosages encumber the development of oral controlled-release formulations because of a short biological half-life (a uniformly compact size, stable at physiological pH, and showed a drug entrapment efficiency of 66.1±5.9 and 65.2±5.6% for Nos-GN and Nos-ES-GN, respectively. The secondary structure of gelatin nanocoacervates was predicted using circular dichroism and in-silico molecular modeling. Our data suggest that ethanol-fabricated GN retained the α-helical content of gelatin, whereas acetone favored the formation of random coils. The conjugation of estrone to Nos-GN did not affect the release rate of the drug, and both formulations followed first-order release kinetics with an initial burst, followed by a slow release. The IC50 value of Nos-ES-GN was 21.2 μmol/l, which was ~50% lower than the free drug (43.3 μmol/l), suggesting targeted drug delivery. Our cell uptake study carried out in an estrogen-receptor-positive (MCF-7) and negative (MDA-MB-231) cancer cell lines showed greater accumulation of Nos-ES-GN in MCF-7 cells instead of MDA-MB-231 cells. Our data indicated that estrone-conjugated nanoparticles may potentially be used for targeting breast cancer cells.
- Madan, Jitender,Gundala, Sushma R.,Kasetti, Yoganjaneyulu,Bharatam, Prasad V.,Aneja, Ritu,Katyal, Anju,Jain, Upendra K.
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- Dual cancer targeting using estrogen functionalized chitosan nanoparticles loaded with doxorubicin-estrone conjugate: A quality by design approach
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In this study, estrone was used as targeting functionality in chitosan nanoparticles (DoxEs-CSEsNPs) carrying doxorubicin-estrone conjugate for dual targeted intracellular delivery to breast cancer cells. Estrone was conjugated with Dox and CS and characterized by FTIR and FT-NMR spectroscopy. Dox/DoxEs containing CSEsNPs were prepared with ionic gelation method and for the effect of formulation variables a 3-factor, 3-level Box-Behnken design (BBD) was explored, which predict the responses like particle size (Y1) and percent entrapment efficiency (%EE) (Y2) when CSEs: TPP ratio (X1), sonication time (X2) and stirring speed (X3) were selected as independent variables. The Dox-CSEsNPs and DoxEs-CSEsNPs were characterized for size, shape, PDI, surface charge and thermal analysis. The drug entrapment efficiency was 66.33 ± 2.82% and 62.25 ± 2.63% for Dox-CSEsNPs and DoxEs-CSEsNPs formulation respectively. The in vitro release, haemolytic toxicity, and fluorescent microscopy studies were also assessed. Anticancer activity on the MCF-7 cell line indicated the higher potency of DoxEs-CSEsNPs as compared to Dox-CSEsNPs, DoxEs, and Dox solution. The findings are decisive for selective targeting of antineoplastic agents to the ERs, which indicate that the DoxEs loaded CSEsNPs were able to significantly improve the efficacy of Dox.
- Kurmi, Balak Das,Paliwal, Rishi,Paliwal, Shivani Rai
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- Oestrone-targeted liposomes for mitoxantrone delivery via oestrogen receptor – synthesis, physicochemical characterization and in-vitro evaluation
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Objectives: Targeted delivery of mitoxantrone (MTO, an anthraquinone drug with high antitumour effect) may be achieved using a novel nanoparticulate delivery system via binding the oestrogen receptor (ER, highly expressed in a variety of human tumours). Methods: A novel liposomal nanoparticle (NP) was developed using a conjugate derived from 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000] (DSPE-PEG2000-NH2) and oestrone (ES, is known to bind the ER) to produce an ES-targeted PEGylated liposome (ES-SSL). The resulting targeted NP was loaded with MTO to produce a targeted liposome-MTO formulation (ES-SSL-MTO). Key findings: The targeted formulation (~140 nm, 1.5 mV) achieved over 95% drug encapsulation efficiency and a favourable stability at 4, 25 and 37 °C up to 48 h. The flow cytometric data indicated that cellular uptake of ES-SSL into human leukaemia HL-60 cells was mediated via binding the oestrogen receptor. In addition, the ES-SSL-MTO significantly reduced the growth of HL-60 cells. Conclusions: Our results provide a proof of principle that ES-modified PEGylated liposomes can target the ER, thereby potentially improving the therapeutic benefits in ER-overexpressed tumours.
- Hao, Qiang,Xu, Guoxing,Yang, Yue,Sun, Yuxin,Cong, Dengli,Li, Hongrui,Liu, Xin,Wang, Zeng,Zhang, Zheng,Chen, Jinglin,Li, Yao,Luan, Xue,Wang, Lin,Tian, Lin,Liu, Kun,Li, Yan,Jiao, Qianru,Pei, Jin
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- Glucagon superfamily peptides exhibiting nuclear hormone receptor activity
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Provided herein are glucagon superfamily peptides conjugated with NHR ligands that are capable of acting at a nuclear hormone receptor. Also provided herein are pharmaceutical compositions and kits of the conjugates of the invention. Further provided here
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Page/Page column 249; 250
(2015/09/28)
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- GLUCAGON SUPERFAMILY PEPTIDES EXHIBITING GLUCOCORTICOID RECEPTOR ACTIVITY
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Provided herein are glucagon superfamily peptides conjugated with GR ligands that are capable of acting at a glucocorticoid receptor. Also provided herein are pharmaceutical compositions and kits of the conjugates of the invention. Further provided herein
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Paragraph 00871
(2013/06/05)
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