Polymeric mixed micelles as nanomedicines: Achievements and perspectives
01 Apr 2017-European Journal of Pharmaceutics and Biopharmaceutics (Eur J Pharm Biopharm)-Vol. 113, pp 211-228
TL;DR: An overview on the current state of the art of several mixed micellar formulations as nanocarriers for drugs and imaging probes, evaluating their ongoing status (preclinical or clinical stage), with special emphasis on type of copolymers, physicochemical properties, in vivo progress achieved so far and toxicity profiles is given.
About: This article is published in European Journal of Pharmaceutics and Biopharmaceutics.The article was published on 2017-04-01. It has received 263 citations till now. The article focuses on the topics: Nanocarriers.
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TL;DR: In this paper, the authors highlight the recent development of smart drug delivery systems for a number of smart nanocarriers, including liposomes, micelles, dendrimers, meso-porous silica nanoparticles, gold nanoparticles and carbon nanotubes.
576 citations
Cites background from "Polymeric mixed micelles as nanomed..."
...This type of arrangement is called a direct or regular polymeric micelle [59,60], depicted in Fig....
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TL;DR: The roles of nanoparticles and hybrid nanoparticles for drug delivery in chemotherapy, targeted therapy, and immunotherapy are discussed and the targeting mechanism of nanoparticle-based drug delivery as well as its function on reversing drug resistance are described.
Abstract: Nanotechnology has been extensively studied and exploited for cancer treatment as nanoparticles can play a significant role as a drug delivery system. Compared to conventional drugs, nanoparticle-based drug delivery has specific advantages, such as improved stability and biocompatibility, enhanced permeability and retention effect, and precise targeting. The application and development of hybrid nanoparticles, which incorporates the combined properties of different nanoparticles, has led this type of drug-carrier system to the next level. In addition, nanoparticle-based drug delivery systems have been shown to play a role in overcoming cancer-related drug resistance. The mechanisms of cancer drug resistance include overexpression of drug efflux transporters, defective apoptotic pathways, and hypoxic environment. Nanoparticles targeting these mechanisms can lead to an improvement in the reversal of multidrug resistance. Furthermore, as more tumor drug resistance mechanisms are revealed, nanoparticles are increasingly being developed to target these mechanisms. Moreover, scientists have recently started to investigate the role of nanoparticles in immunotherapy, which plays a more important role in cancer treatment. In this review, we discuss the roles of nanoparticles and hybrid nanoparticles for drug delivery in chemotherapy, targeted therapy, and immunotherapy and describe the targeting mechanism of nanoparticle-based drug delivery as well as its function on reversing drug resistance.
338 citations
TL;DR: In this paper, a review of different characterization techniques for polymeric micelles is presented, from the ones used for the determination of micells basic characteristics (critical micellar concentration, size, surface charge, morphology) to the more complex approaches used to figure out micellers kinetic stability, drug release and behavior in the presence of biological substrates (fluids, cells and tissues).
264 citations
TL;DR: This review will focus on the potential of pH-sensitive micells in tumor therapy, analyze four types of drug-loaded micelles and mechanisms of drug release and give an exhaustive collection of recent investigations.
178 citations
Cites background from "Polymeric mixed micelles as nanomed..."
...…micelles have the following characteristics: excellent biocompatibility; suitable particle size (<200nm); prolonged circulation time in the blood after intravenous injection; and can carry anti-tumor drugs passively targeted and accumulated in the tumor via the EPR effects (Cagel et al., 2017)....
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...(<200nm); prolonged circulation time in the blood after intravenous injection; and can carry anti-tumor drugs passively targeted and accumulated in the tumor via the EPR effects (Cagel et al., 2017)....
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TL;DR: The prepared Exo-Dox showed enhanced cellular uptake efficiency and anti-tumor effect in osteosarcoma MG63 cell line but low cytotoxicity in myocardial H9C2 cell line, suggesting it could be used as an excellent chemotherapeutic drug for treatment of osteosARcoma in vitro.
Abstract: Purpose The primary goal of the present study was to develop the nano-drug consisting of doxorubicin and exosome derived from mesenchymal stem cells, and to explore its effect on osteosarcoma in vitro. Methods The exosomes were isolated from bone marrow MSCs (BM-MSCs) by an Exosome Isolation Kit. The exosome-loaded doxorubicin (Exo-Dox) was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM) were used to characterize of the exosome and Exo-Dox. The cytotoxicity of Exo-Dox was determined by CCK-8 assay. Further, the cellular uptake of different drugs was analyzed using inverted fluorescence microscope and flow cytometry. Results The typical exosome structures can be observed by TEM. After loading with doxorubicin, its size is larger than free exosome. Compared with the free Dox, the prepared Exo-Dox showed enhanced cellular uptake efficiency and anti-tumor effect in osteosarcoma MG63 cell line but low cytotoxicity in myocardial H9C2 cell line. Conclusion The prepared Exo-Dox could be used as an excellent chemotherapeutic drug for treatment of osteosarcoma in vitro. Considering the tumor-homing feature of BM-MSCs, the Exo-Dox may be a good candidate for targeted osteosarcoma treatment in future study.
149 citations
References
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TL;DR: First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy.
Abstract: In the planned interim analysis of data for the first 200 patients, progression-free survival was significantly longer in the gefitinib group than in the standard-chemotherapy group (hazard ratio for death or disease progression with gefitinib, 0.36; P<0.001), resulting in early termination of the study. The gefitinib group had a significantly longer median progression-free survival (10.8 months, vs. 5.4 months in the chemotherapy group; hazard ratio, 0.30; 95% confidence interval, 0.22 to 0.41; P<0.001), as well as a higher response rate (73.7% vs. 30.7%, P<0.001). The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group (P = 0.31). The most common adverse events in the gefitinib group were rash (71.1%) and elevated amino transferase levels (55.3%), and in the chemotherapy group, neutropenia (77.0%), anemia (64.6%), appetite loss (56.6%), and sensory neuropathy (54.9%). One patient receiving gefitinib died from interstitial lung disease. CONCLUSIONS First-line gefitinib for patients with advanced non–small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy. (UMIN-CTR number, C000000376.)
4,829 citations
TL;DR: In this article, it was shown that in the presence of polar solvents, there is a significant enhancement in the intensity of the 0-0 vibronic band at the expense of other bands.
Abstract: The fluorescence intensities for various vibronic fine structures in the pyrene monomer fluorescence show strong solvent dependence. In the presence of polar solvents, there is a significant enhancement in the intensity of the 0--0 vibronic band at the expense of other bands. This strong perturbation in the vibronic band intensities is more dependent on the solvent dipole moment than on the bulk solvent dielectric constant. This suggests the operation of some specific solute--solvent dipole--dipole interaction mechanism. The strong perturbation of the vibronic band intensities has been used as a probe to accurately determine critical micelle concentrations and also to investigate the extent of water penetration in micellar systems.
3,271 citations
"Polymeric mixed micelles as nanomed..." refers background in this paper
...When micelles are formed, pyrene is preferentially partitioned on the hydrophobic core and thus, a CMC value can be determined [59]....
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TL;DR: This review summarizes historical and scientific perspectives of Doxil development and lessons learned from its development and 20 years of its use and demonstrates the obligatory need for applying an understanding of the cross talk between physicochemical, nano-technological, and biological principles.
3,189 citations
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...However, it presents several adverse effects, including nausea, vomiting, stomatitis, alopecia, myelosuppression and dose-dependent cardiotoxicity (550 mg/m2 is the maximum allowed cumulative dose) [79]....
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TL;DR: It is shown that the penetration and efficacy of the larger micelles could be enhanced by using a transforming growth factor-β inhibitor to increase the permeability of the tumours.
Abstract: Drug-loaded polymeric micelles with a diameter of 30 nm can penetrate poorly permeable tumours to achieve an antitumour effect.
2,026 citations
"Polymeric mixed micelles as nanomed..." refers background in this paper
...altered pharmacokinetics: longer mean residence time (MRT) of the drug in the bloodstream [14-17]; increased bioavailability [18]; reduced administered dose and possible diminished of non-specific organ toxicity as a result of more precise drug delivery to target tissues [14]....
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TL;DR: A general overview of the preparation, characterization and theories of block copolymer micellar systems is presented in this paper, with examples of micelle formation in aqueous and organic medium are given for di-and triblock copolymers, as well as for more complex architectures.
1,856 citations
"Polymeric mixed micelles as nanomed..." refers background in this paper
...This thermodynamically driven process occurs above a copolymer determined concentration, commonly known as critical micellar concentration (CMC) [5-6]....
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