Block copolymer micelles for drug delivery: design, characterization and biological significance
TL;DR: The utility of polymeric micelles formed through the multimolecular assembly of block copolymers as novel core-shell typed colloidal carriers for drug and gene targeting and their feasibility as non-viral gene vectors is highlighted.
About: This article is published in Advanced Drug Delivery Reviews.The article was published on 2001-03-23. It has received 3457 citations till now. The article focuses on the topics: Micelle & Targeted drug delivery.
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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
TL;DR: There is a highly promising role of stimuli-responsive nanocarrier systems for drug and gene delivery in the future with greater understanding of the difference between normal and pathological tissues and cells.
1,993 citations
Cites background from "Block copolymer micelles for drug d..."
...Micelles are spherical supramolecular nanoassemblies ranging from 20 to 100 nm in size that have attracted considerable interest as potential drug nanocarriers due to their unique properties such as high solubility, high drug loading capacity and low toxicity [104]....
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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
Cites background from "Block copolymer micelles for drug d..."
...In continuation of their pioneering work on polymeric micelles as drug release systems Kataoka and co-worker [299,301,315] have introduced the concept of active targeting for micellar systems....
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TL;DR: A background to investigators new to stealth nanoparticles is presented, and some key considerations needed prior to designing a nanoparticle PEGylation protocol and characterizing the performance features of the product are suggested.
1,791 citations
TL;DR: Fluorescent Chemosensors Based on Spiroring-Opening of Xanthenes and Related Derivatives and their applications in Nano Science and Bioinspired Science.
Abstract: Fluorescent Chemosensors Based on Spiroring-Opening of Xanthenes and Related Derivatives Xiaoqiang Chen, Tuhin Pradhan, Fang Wang, Jong Seung Kim,* and Juyoung Yoon* Departments of Chemistry and Nano Science and of Bioinspired Science (WCU), Ewha Womans University, Seoul 120-750, Korea State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemistry and Chemical Engineering, Nanjing University of Technology, Nanjing 210009, China Department of Chemistry, Korea University, Seoul 136-701, Korea
1,719 citations
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TL;DR: It is speculated that the tumoritropic accumulation of smancs and other proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels in tumors of tumor-bearing mice.
Abstract: We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.
6,483 citations
TL;DR: Together, these properties make PEI a promising vector for gene therapy and an outstanding core for the design of more sophisticated devices because its efficiency relies on extensive lysosome buffering that protects DNA from nuclease degradation, and consequent lysOSomal swelling and rupture that provide an escape mechanism for the PEI/DNA particles.
Abstract: Several polycations possessing substantial buffering capacity below physiological pH, such as lipopolyamines and polyamidoamine polymers, are efficient transfection agents per se--i.e., without the addition of cell targeting or membrane-disruption agents. This observation led us to test the cationic polymer polyethylenimine (PEI) for its gene-delivery potential. Indeed, every third atom of PEI is a protonable amino nitrogen atom, which makes the polymeric network an effective "proton sponge" at virtually any pH. Luciferase reporter gene transfer with this polycation into a variety of cell lines and primary cells gave results comparable to, or even better than, lipopolyamines. Cytotoxicity was low and seen only at concentrations well above those required for optimal transfection. Delivery of oligonucleotides into embryonic neurons was followed by using a fluorescent probe. Virtually all neurons showed nuclear labeling, with no toxic effects. The optimal PEI cation/anion balance for in vitro transfection is only slightly on the cationic side, which is advantageous for in vivo delivery. Indeed, intracerebral luciferase gene transfer into newborn mice gave results comparable (for a given amount of DNA) to the in vitro transfection of primary rat brain endothelial cells or chicken embryonic neurons. Together, these properties make PEI a promising vector for gene therapy and an outstanding core for the design of more sophisticated devices. Our hypothesis is that its efficiency relies on extensive lysosome buffering that protects DNA from nuclease degradation, and consequent lysosomal swelling and rupture that provide an escape mechanism for the PEI/DNA particles.
6,213 citations
TL;DR: The platinum compounds inhibit sarcoma 180 and leukaemia L1210 in mice and reversibly inhibit cell division in Gram-negative rods1–4.
Abstract: CERTAIN platinum compounds completely but reversibly iiihibit cell division in Gram-negative rods1–4. These compounds have been tested for antitumour activity and we report some of the preliminary results. The platinum compounds inhibit sarcoma 180 and leukaemia L1210 in mice.
3,574 citations
TL;DR: Monodisperse biodegradable nanospheres were developed from amphiphilic copolymers composed of two biocompatible blocks and exhibited dramatically increased blood circulation times and reduced liver accumulation in mice.
Abstract: Injectable nanoparticulate carriers have important potential applications such as site-specific drug delivery or medical imaging. Conventional carriers, however, cannot generally be used because they are eliminated by the reticulo-endothelial system within seconds or minutes after intravenous injection. To address these limitations, monodisperse biodegradable nanospheres were developed from amphiphilic copolymers composed of two biocompatible blocks. The nanospheres exhibited dramatically increased blood circulation times and reduced liver accumulation in mice. Furthermore, they entrapped up to 45 percent by weight of the drug in the dense core in a one-step procedure and could be freeze-dried and easily redispersed without additives in aqueous solutions.
2,827 citations
TL;DR: In this article, the authors focused on the promising features of block copolymer micelles as drug vehicles mimicking the natural carrier-systems with supramolecular structures (i.e. viruses and lipoproteins).
1,006 citations