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Docetaxel and nanoparticles

Jitendrakumar Patel, Jitendra Amrutiya, Priyanka Bhatt, Ankit Javia, Mukul Jain, Ambikanandan Misra
Aim of this study was to develop anti EGFR antibody conjugated poly (lactide-co-glycolide) nanoparticles (NPs) to target epidermal growth factor receptor, highly expressed on non-small cell lung cancer cells to improve cytotoxicity and site specificity. Cetuximab was conjugated to Docetaxel loaded PLGA NPs by known EDC/NHS chemistry and characterized for size, zeta potential, conjugation efficiency and results were 128.4 ±3.6 nm, -31.0 ± 0.8 mV and 39.77 ± 3.4% respectively. In-vitro release study demonstrated sustained release of drug from NPs with 25% release at pH 5...
March 15, 2018: Journal of Microencapsulation
Xing Chen, Lili Zhao, Yang Kang, Zhiyu He, Fei Xiong, Xiang Ling, Jun Wu
Non-small-cell lung cancer (NSCLC) accounts for over 85% of clinical lung cancer cases, which is the leading cause of cancer-related death. To develop new therapeutic strategy for NSCLC, a library of L-phenylalanine-based poly(ester amide) (Phe-PEA) polymers was synthesized and assembled with docetaxel (Dtxl) to form Dtxl-loaded Phe-PEA nanoparticles (NPs). The hydrophobic Phe-PEA polymers were able to form NPs by nanoprecipitation method and the characterization results showed that the screened Dtxl-8P4 NPs have small particle size (∼100 nm) and high Dtxl loading (∼20 wt%)...
2018: Frontiers in Pharmacology
Claudia Conte, Francesca Mastrotto, Vincenzo Taresco, Aleksandra Tchoryk, Fabiana Quaglia, Snjezana Stolnik, Cameron Alexander
In the treatment of lung cancer, there is an urgent need of innovative medicines to optimize pharmacological responses of conventional chemotherapeutics while attenuating side effects. Here, we have exploited some relatively unexplored subtle differences in reduction potential, associated with cancer cell microenvironments in addition to the well-known changes in intracellular redox environment. We report the synthesis and application of novel redox-responsive PLGA (poly(lactic-co-glycolic acid)) -PEG (polyethylene glycol) nanoparticles (RR-NPs) programmed to change surface properties when entering tumor microenvironments, thus enhance cell internalization of the particles and their drug cargo...
March 10, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Na Kong, Mei Deng, Xiu-Na Sun, Yi-Ding Chen, Xin-Bing Sui
Current limitations of cancer therapy include the lack of effective strategy for target delivery of chemotherapeutic drugs, and the difficulty of achieving significant efficacy by single treatment. Herein, we reported a synergistic chemo-photothermal strategy based on aptamer (Apt)-polydopamine (pD) functionalized CA-(PCL- ran -PLA) nanoparticles (NPs) for effective delivery of docetaxel (DTX) and enhanced therapeutic effect. The developed DTX-loaded Apt-pD-CA-(PCL- ran -PLA) NPs achieved promising advantages, such as (i) improved drug loading content (LC) and encapsulation efficiency (EE) initiated by star-shaped copolymer CA-(PCL- ran -PLA); (ii) effective target delivery of drugs to tumor sites by incorporating AS1411 aptamers; (iii) significant therapeutic efficacy caused by synergistic chemo-photothermal treatment...
2018: Frontiers in Pharmacology
Man Ao, Xu Xiao, Yazhou Ao
In the present study, we successfully developed a docetaxel (DTX) and thalidomide (TDD) co-delivery system based on low density lipoprotein (LDL) modified silica nanoparticles (LDL/SLN/DTX/TDD). By employing the tumor homing property of LDL and the drug-loading capability of silica nanoparticles, the prepared LDL/SLN/DTX/TDD was expected to locate and specifically deliver the loaded drugs (DTX and TDD) to achieve effective chemotherapy of liver cancer. In vitro analysis revealed that nano-sized LDL/SLN/DTX/TDD with decent drug loading capabilities was able to increase the delivery efficiency by targeting the low density lipoprotein receptors, which were overexpressed on HepG2 human hepatocellular liver carcinoma cell line, which exerted better cytotoxicity than unmodified silica nanoparticles and free drugs...
January 23, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Jee Young Chung, Jae Ho Ko, Ye Ji Lee, Hyung Seok Choi, Yong-Hee Kim
Docetaxel, an advanced taxoid, has been widely used as an anti-mitotic agent, but further augmentation of its properties is still required, including improvement in low aqueous solubility. Herein, we report the development of bio-eliminable low molecular weight methylcellulose-based surfactant-free injectable formulation for the delivery of docetaxel. Crude methylcellulose, a hydrophobically modified cellulose derivative, was hydrolyzed by an enzymatic degradation method to obtain low molecular weight methylcellulose (LMwMC)...
February 21, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Qingshuo Meng, Jia Meng, Wei Ran, Junyang Wang, Yihui Zhai, Pengcheng Zhang, Yaping Li
Triple-negative breast cancer (TNBC) tumors are heterogeneous, with mesenchymal-like cells at their core and fast proliferating cells on the periphery. It is desirable and beneficial to treat TNBC cells of different phenotypes with the most appropriate drugs. Here, we report a 78 nm, chlorin e6-, docetaxel-, and anti-Twist siRNA-containing polymeric nanoparticle (CDTN) with spatiotemporally specific activity when irradiated by light. Under conditions mimicking superficial tumor tissue with sufficient light input, TNBC cells are mainly killed by the photodynamic therapy (PDT) function of CDTNs...
February 22, 2018: ACS Nano
Shaohui Zheng, Jiwon Han, Zhen Jin, Chang-Sei Kim, Sukho Park, Kyu-Pyo Kim, Jong-Oh Park, Eunpyo Choi
Multifunctional polymeric micelles were developed as a promising dual tumor-targeted drug delivery platform for magnetic resonance (MR) imaging and combined photothermal-chemotherapy. HA-C16 copolymers were synthesized via peptide formation process with subsequent co-encapsulation of therapeutic agent docetaxel (DTX) and superparamagnetic iron oxide nanoparticles (SPIONs) to form the multifunctional micelles. The micelles exhibited uniform nanosize and remarkable colloidal stability in aqueous solution. The sustained drug release behavior from HA micelles was observed over the test period...
February 5, 2018: Colloids and Surfaces. B, Biointerfaces
Yifei Guo, Shuang Zhao, Hanhong Qiu, Ting Wang, Yanna Zhao, Meihua Han, Zhengqi Dong, Xiangtao Wang
It was reported that the shape of nanocarriers played an important role in achieving better therapeutic effect. To optimize the morphology and enhance the antitumor efficacy, in this study based on the amphiphilic PAMAM-b-OEG codendrimer (POD), docetaxel-loaded spherical and flake-like nanoparticles (DTX nanospheres and nanosheets) were prepared via antisolvent precipitation method with the similar particle size, surface charge, stability, and release profiles. The feed weight ratio of DTX/POD and the branched structure of OEG dendron were suggested to influence on the shapes of the self-assembled nanostructures...
February 9, 2018: Bioconjugate Chemistry
Erfaneh Ghassami, Jaleh Varshosaz, Ali Jahanian-Najafabadi, Mohsen Minaiyan, Parvin Rajabi, Effat Hayati
Purpose: Epithelixal ovarian cancer is the fourth cause of cancer death in developed countries with 77% of ovarian cancer cases diagnosed with regional or distant metastasis, with poor survival rates. Docetaxel (DTX) is a well-known anticancer agent, with clinically proven efficacy in several malignancies, including ovarian cancer. However, the adverse effects caused by the active ingredient or currently marketed formulations could even deprive the patient of the advantages of treatment...
2018: International Journal of Nanomedicine
Ya-Xuan Zhu, Hao-Ran Jia, Guang-Yu Pan, Nathan W Ulrich, Zhan Chen, Fu-Gen Wu
Research on nanomedicines has rapidly progressed in the last few years. However, due to the limited size of nuclear pores (9-12 nm), the nuclear membrane remains a difficult barrier to many nucleus-targeting agents. Here, we report the development of a general platform to effectively deliver chemical compounds such as drug molecules or nanomaterials into cell nuclei. This platform consists of a polyamine unit polyhedral oligomeric silsesquioxane (POSS), a hydrophilic polyethylene glycol (PEG) chain, and a photosensitizer rose bengal (RB), which can self-assemble into nanoparticles (denoted as PPR NPs)...
February 6, 2018: Journal of the American Chemical Society
Wei Zhang, Yunmei Song, Preethi Eldi, Xiuli Guo, John D Hayball, Sanjay Garg, Hugo Albrecht
Prostate cancer cells frequently overexpress the gastrin-releasing peptide receptor, and various strategies have been applied in preclinical settings to target this receptor for the specific delivery of anticancer compounds. Recently, elastin-like polypeptide (ELP)-based self-assembling micelles with tethered GRP on the surface have been suggested to actively target prostate cancer cells. Poorly soluble chemotherapeutics such as docetaxel (DTX) can be loaded into the hydrophobic cores of ELP micelles, but only limited drug retention times have been achieved...
2018: International Journal of Nanomedicine
Mengrui Liu, Hongliang Du, Abdur Rauf Khan, Jianbo Ji, Aihua Yu, Guangxi Zhai
In this report, redox/enzyme responsive chondroitin sulfate-ss-deoxycholic acid (CSCD) conjugates were synthesized using cystamine as the linkage which could self-assemble to form self-assembled nanoparticles (175.6 + 5.2 nm) in the aqueous environment. Docetaxel (DTX) was loaded in nanoparticles with desired loading efficiency for the inhibition of tumor growth and metastasis of melanoma. Interestingly, nanoparticles were demonstrated to respond to hyaluronidase-1 (Hyal-1) which could degrade chondroitin sulfate (CS) backbones...
March 15, 2018: Carbohydrate Polymers
Jaleh Varshosaz, Erfaneh Ghassami, Abdollah Noorbakhsh, Ali Jahanian-Najafabadi, Mohsen Minaiyan, Ramezan Behzadi
OBJECTIVES: Ovarian cancer is still a major cause of morbidity and mortality. Docetaxel (DTX) is one of the most notable cytotoxic agents for treatment of ovarian cancer. However, its side-effects proposed considerable problems to the patients. SIGNIFICANCE: Polymeric nanoparticles (NPs) of poly (butylene adipate-co-butylene terephthalate) (Ecoflex®), a biodegradable and biocompatible polymer, were prepared for the first time by the upgradeable electrospraying technique...
January 18, 2018: Drug Development and Industrial Pharmacy
Sheryhan F Gad, Joonyoung Park, Ji Eun Park, Gihan N Fetih, Sozan S Tous, Wooin Lee, Yoon Yeo
Intravenous delivery of poorly water-soluble anticancer drugs such as docetaxel (DTX) is challenging due to the low bioavailability and the toxicity related to solubilizing excipients. Colloidal nanoparticles are used as alternative carriers, but low drug loading capacity and circulation instability limit their clinical translation. To address these challenges, DTX nanocrystals (NCs) were prepared using Pluronic F127 as an intermediate stabilizer and albumin as a functional surface modifier, which were previously found to be effective in producing small and stable NCs...
January 17, 2018: Molecular Pharmaceutics
Gantumur Battogtokh, Oyuntuya Gotov, Jee He Kang, Jinsung Cho, Tae Ho Jeong, Ganzorig Chimed, Young Tag Ko
AIM: The objective of this study was to develop a mitochondria-targeted anticancer drug, docetaxel (DTX), for chemotherapy. MATERIALS & METHODS: The DTX was conjugated to 4-carboxybutyl triphenylphosphonium (TPP) to enhance mitochondrial targeting, and the TPP-DTX conjugate was further loaded into folate-cholesteryl albumin (FA-chol-BSA) nanoparticles (NPs) to improve its biocompatibility. RESULTS & CONCLUSION: In vitro studies showed that TPP-DTX and its NP primarily accumulated in the mitochondria; generated high reactive oxygen species, leading to mitochondrial disruption and cell apoptosis; and had a higher cytotoxicity against cancer cells...
January 17, 2018: Nanomedicine
Chang Chih-Chun, Yang Yang, Dong-Yu Gao, Hui-Teng Cheng, Bryan Hoang, Po-Han Chao, Ling-Hsuan Chen, Joseph Bteich, Tsaiyu Chiang, Jia-Yu Liu, Shyh-Dar Li, Yunching Chen
Chronic liver diseases have recently garnered substantial attention as a leading cause of death around the world. During the progression of liver fibrosis/cirrhosis induced by chronic liver injury, hepatic stellate cells (HSCs) play key roles in the regulation of liver fibrogenesis and can even accelerate the progression of hepatocellular carcinoma (HCC). Thus, inhibition of HSC activation or suppression of inflammatory cytokine secretion by HSCs may be an efficient therapeutic strategy to ameliorate liver fibrosis/cirrhosis...
December 18, 2017: Journal of Drug Targeting
Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P Zhou, Mien-Chie Hung, Xiaoming Xie
Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS)...
2017: Theranostics
Guolian Ren, Pei Chen, Jiaqi Tang, Rongrong Wang, Shuai Duan, Ruili Wang, Yin Xie, Shuqiu Zhang
Docetaxel (DTX) solution has some serious adverse side effects. A redox-responsive DTX prodrug synthesized in our laboratory was used to prepare DTX prodrug self-assembled nanoparticles (DSNPs) with the method of nanoprecipitation. This study aimed at optimizing the formulation to develop stable preparation for the delivery of DTX. Single-factor test was used to evaluate the effects of the preparation concentration of DTX prodrug, stirring speed, the types of stabilizers and temperature on the prescription process of DSNPs...
April 2018: Drug Development and Industrial Pharmacy
Huibo Lian, Jinhui Wu, Yiqiao Hu, Hongqian Guo
Resistance to regular treatment strategies is a big challenge in the treatment of castration-resistant prostate cancer. Combination of photothermal and photodynamic therapy (PTT/PDT) with chemotherapy offers unique advantages over monotherapy alone. However, free drugs, such as photosensitizers and chemotherapeutic agents, lack tumor-targeted accumulation and can be easily eliminated from the body. Moreover, most of the PTT drugs are hydrophobic and their organic solvents have in vivo toxicity, thereby limiting their potential in clinical translation...
2017: International Journal of Nanomedicine
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