PEGylated Chitosan Nanoparticles Potentiate Repurposing of Ormeloxifene in Breast Cancer Therapy

Agrawal, Satish; Ahmad, Hafsa; Dwivedi, Monika; Shukla, Mahendra; Arya, Abhishek; Sharma, Komal; Lal, Jawahar; Dwivedi, Anil Kumar

doi:10.2217/nnm-2016-0095

Cited by 34 publications

(15 citation statements)

References 58 publications

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“…In other study, CH-based NPs were prepared by layer-by-layer technique for the incorporation of Gem and platinum aiming at lung cancer treatments [38]. Other studies reported the use of CH-based NPs for the delivery of other antitumor drugs: PEG-layered CH NPs enhanced the efficacy of ormeloxifene in breast cancer [39] and platinum-gold NPs with CH and doxorubicin presented cell-specific cytotoxicity [40].…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine Delivered by Fucoidan/Chitosan Nanoparticles Presents Increased Toxicity Over Human Breast Cancer Cells

Oliveira

Neves

Reis

et al. 2018

Nanomedicine (Lond.)

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Section: Discussionmentioning

confidence: 99%

Gemcitabine Delivered by Fucoidan/Chitosan Nanoparticles Presents Increased Toxicity Over Human Breast Cancer Cells

Oliveira

Neves

Reis

et al. 2018

Nanomedicine (Lond.)

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“…4 a – c ). The absence of crystalline peak of chitosan in the Cs PEG placebo nanocapsules revealed the conformational transformation of chitosan from semi‐crystalline to amorphous due to its ionic gelation with negatively charged particles [10]. The disappearance of crystalline peak of TQ in the Cs PEG nanocapsules loaded with TQ confirmed the molecular dispersion of TQ within the Cs PEG nanocapsules [27].…”

Section: Resultsmentioning

confidence: 99%

“…PEGylated chitosan has been successfully used for the encapsulating drugs such as methotrxate, mitomycin C, ormeloxifene etc. [10,[21][22][23]. The PEGylated chitosan nanocapsules are reported to exhibit dual role in both invitro and invivo studies [22,24].…”

Section: Introductionmentioning

confidence: 99%

“…It is readily degraded into simple metabolising sugars and has good mucoadhesive and membrane permeability–enhancing properties [9]. The positive nature of chitosan serves for enhanced cellular interaction, delivery and increased penetration capacity in heterogeneous tumours [10]. The large number of free amine groups present in chitosan backbone when compared with other biodegradable polymers assists binding of many bioactive agents to the polymer [11].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and characterisation of PEG modified chitosan nanocapsules loaded with thymoquinone

Kumar

Devi

Harish

et al. 2016

IET nanobiotechnol.

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Thymoquinone (TQ), a major bioactive compound of seeds has several therapeutic properties. The main drawback in bringing TQ to therapeutic application is that it has poor stability and bioavailability. Hence a suitable carrier is essential for TQ delivery. Recent studies indicate biodegradable polymers are potentially good carriers of bioactive compounds. In this study, polyethylene glycol (PEG) modified chitosan (Cs) nanocapsules were developed as a carrier for TQ. Aqueous soluble low molecular weight Cs and PEG was selected among different biodegradable polymers based on their biocompatibility and efficacy as a carrier. Optimisation of synthesis of nanocapsules was done based on particle size, PDI, encapsulation efficiency and process yield. A positive zeta potential value of +48 mV, indicating good stability was observed. Scanning electron microscope and atomic-force microscopy analysis revealed spherical shaped and smooth surfaced nanocapsules with size between 100 to 300 nm. The molecular dispersion of the TQ in Cs PEG nanocapsules was studied using X-ray powder diffraction. The Fourier transform infrared spectrum of optimised nanocapsule exhibited functional groups of both polymer and drug, confirming the presence of Cs, PEG and TQ. In vitro drug release studies showed that PEG modified Cs nanocapsules loaded with TQ had a slow and sustained release.

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“…But the use of tamoxifen is reported to cause resistance after some years of therapy and increases the incidence of endometrial cancer by threefold and cause many complications including deep vein thrombosis, pulmonary embolism, DNA adducts formation, and liver cancer risk (Minsun, ). Ormeloxifene (ORM) is a potent nonsteroidal agent that has been widely shown to act upon several important molecular targets in cancer cell lines (Figure ) (Nigam, Singh, Ranjan, Zaidi, & Sharma, , Nigam, Ranjan, Srivastava, Sharma, & Balapure, ; Misra, Nigam, Gupta, Agarwal, & Kamboj, ; Kaushik, Shyam, Sharma, & Balapure, ; Jayant, Shweta, Srikantha, & Anil, ; Agrawal et al, ; Khan et al, ; Ramaraju et al, ; Khan, Shukla, Sinha, & Meeran, ; Singh, Zaidi, Shyam, Sharma, & Balapure, ; Mishra et al, ; Dhar & Srivastava, ; Mukhopadhyay, Gupta, Ray, & Giri, ; Mukhopadhyay, Ray, & Giri, ; Giri, Mukhopadhyay, Sun, Hsie, & Ray, ; Arindam et al, ). The molecule was developed by the Central Drug Research Institute, Lucknow, India, and marketed by HLL Lifecare limited, India, under the brand name of Saheli, Novex, and Novex‐DS (Nityanand & Anand, ).…”

Section: Introductionmentioning

confidence: 99%

Nonhormonal selective estrogen receptor modulator 1‐(2‐[4‐{(3R,4S)‐7‐Methoxy‐2, 2‐dimethyl‐3‐phenyl‐chroman‐4yl}phenoxy]ethyl)pyrrolidine hydrochloride (ormeloxifene hydrochloride) for the treatment of breast cancer

Pillai

Regidi

Varghese

et al. 2018

Drug Development Research

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Breast cancer is the most common type of diagnosed cancers in women, difficult to treat, and has received international attention because of its aggressive nature and inherent drug resistance mechanisms. Development of a better selective estrogen receptor modulator with good therapeutic profile and less toxicity is very crucial in this scenario. This study was undertaken to evaluate and compare the in vitro and in vivo antitumor activities of ormeloxifene with other clinically used breast cancer drugs. Cytotoxic activity of ormeloxifene was compared with standard drugs, 4‐hydroxytamoxifene and Adriamycin. Ormeloxifene (50 μM) concentration showed cytotoxicity of 75% and 82% in MDAMB‐231 and 24% and 80% in MCF‐7 cells, respectively, after 72 and 144 hr of incubation as displayed by cell viability assay. The same concentration of ormeloxifene was shown to exert 74% caspase‐7 activation in MCF‐7 cells after 24 hr of incubation by fluorescence resonance energy transfer assay. Cell cycle analysis proved that there was an increase in sub‐G1 peak to 64.4% and 33.9% in MDAMB‐231 and MCF‐7 cells, respectively, after treatment using ormeloxifene (50 μM) for 48 hr. The nonobese diabetic‐severe combined immunodeficiency mice bearing tumor xenografts of triple negative MDAMB‐231 cells treated with ormeloxifene (3 mg/kg bw) showed significant regression in relative tumor volume compared to control. From the results obtained and as evidenced from prior literature, ormeloxifene in addition to contraceptive use, can be repositioned for the development of an efficacious anticancer drug. These data present the preclinical part of a well concerted effort to place ormeloxifene into further clinical trials.

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PEGylated Chitosan Nanoparticles Potentiate Repurposing of Ormeloxifene in Breast Cancer Therapy

Abstract: PEGylated CNPs enhanced anticancer activity of ormeloxifene.

Cited by 34 publications

References 58 publications

Gemcitabine Delivered by Fucoidan/Chitosan Nanoparticles Presents Increased Toxicity Over Human Breast Cancer Cells

Gemcitabine Delivered by Fucoidan/Chitosan Nanoparticles Presents Increased Toxicity Over Human Breast Cancer Cells

Synthesis and characterisation of PEG modified chitosan nanocapsules loaded with thymoquinone

Nonhormonal selective estrogen receptor modulator 1‐(2‐[4‐{(3R,4S)‐7‐Methoxy‐2, 2‐dimethyl‐3‐phenyl‐chroman‐4yl}phenoxy]ethyl)pyrrolidine hydrochloride (ormeloxifene hydrochloride) for the treatment of breast cancer

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