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Glioma is a serious life-threatening disease, and traditional treatments have little effect. In recent decades, polymer materials have been developed for the treatment of glioma as a new research area. The ability to target reactive polymeric carriers is important for treating glioma. Polymer materials have good designability and expansibility. They respond to different stimuli, leading to a change in the macroscopic properties of materials. Sensitive polymer carriers respond to biological stimuli (pH, oxidative stress, enzyme, temperature, ions and nucleic acids) and the tumour microenvironment. They can be used as intelligent polymer carriers to transport chemotherapy and imaging drugs for glioma treatment. The ability of these polymer carriers to control the release of molecules at tumour-specific sites has aroused great interest. This review summarizes current research on sensitive polymer-carriers for glioma treatment over the past decade, focusing on their clinical application prospects. Finally, future applications of polymer carriers in nanomedicine are reviewed.

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Photo/radiosensitizers, such as octahedral molybdenum clusters (Mo6), have been intensively studied for photodynamic applications to treat various diseases. However, their delivery to the desired target can be hampered by its limited solubility, low stability in physiological conditions, and inappropriate biodistribution, thus limiting the therapeutic effect and increasing the side effects of the therapy. To overcome such obstacles and to prepare photofunctional nanomaterials, we employed biocompatible and water-soluble copolymers based on N-(2-hydroxypropyl)methacrylamide (pHPMA) as carriers of Mo6 clusters. Several strategies based on electrostatic, hydrophobic, or covalent interactions were employed for the formation of polymer-cluster constructs. Importantly, the luminescent properties of the Mo6 clusters were preserved upon association with the polymers: all polymer-cluster constructs exhibited an effective quenching of their excited states, suggesting a production of singlet oxygen (O2(1Δg)) species which is a major factor for a successful photodynamic treatment. Even though the colloidal stability of all polymer-cluster constructs was satisfactory in deionized water, the complexes prepared by electrostatic and hydrophobic interactions underwent severe aggregation in phosphate buffer saline (PBS) accompanied by the disruption of the cohesive forces between the cluster and polymer molecules. On the contrary, the conjugates prepared by covalent interactions notably displayed colloidal stability in PBS in addition to high luminescence quantum yields, suggesting that pHPMA is a suitable nanocarrier for molybdenum cluster-based photosensitizers intended for photodynamic applications.

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Nanomaterials have aroused attention in the recent years for their high potential for gene delivery applications. Most of the nanoformulations used in gene delivery are positively charged to carry negatively charged oligonucleotides. However, excessive positively charged carriers are cytotoxic. Therefore, the complexed oligonucleotide/nanoparticles should be well-examined before the application. In that manner, agarose gel electrophoresis, which is a basic method utilized for separation, identification, and purification of nucleic acid molecules because of its poriferous nature, is one of the strategies to determine the most efficient complexation rate. When the electric field is applied, RNA fragments can migrate through anode due to the negatively charged phosphate backbone. Because RNA has a uniform mass/charge ratio, RNA molecules run in agarose gel proportional according to their size and molecular weight. In this chapter, the determination of complexation efficiency between cationic polymer carriers and small interfering RNA (siRNA) cargos by using agarose gel electrophoresis is described. siRNA/cationic polymer carrier complexes are placed in an electric field and the charged molecules move through the counter-charged electrodes due to the phenomenon of electrostatic attraction. Nucleic acid cargos are loaded to cationic carriers via the electrostatic interaction between positively charged amine groups (N) of the carrier and negatively charged phosphate groups (P) of RNA. The N/P ratio determines the loading efficiency of the cationic polymer carrier. In here, the determination of N/P ratio, where the most efficient complexation occurs, by exposure to the electric field with a gel retardation assay is explained.

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Drug repurposing is a promising strategy for identifying new applications for approved drugs. Here, we describe a polymer biomaterial composed of the antiretroviral drug ritonavir derivative (5-methyl-4-oxohexanoic acid ritonavir ester; RD), covalently bound to HPMA copolymer carrier via a pH-sensitive hydrazone bond (P-RD). Apart from being more potent inhibitor of P-glycoprotein in comparison to ritonavir, we found RD to have considerable cytostatic activity in six mice (IC50 ~ 2.3-17.4 µM) and six human (IC50 ~ 4.3-8.7 µM) cancer cell lines, and that RD inhibits the migration and invasiveness of cancer cells in vitro. Importantly, RD inhibits STAT3 phosphorylation in CT26 cells in vitro and in vivo, and expression of the NF-κB p65 subunit, Bcl-2 and Mcl-1 in vitro. RD also dampens chymotrypsin-like and trypsin-like proteasome activity and induces ER stress as documented by induction of PERK phosphorylation and expression of ATF4 and CHOP. P-RD nanomedicine showed powerful antitumor activity in CT26 and B16F10 tumor-bearing mice, which, moreover, synergized with IL-2-based immunotherapy. P-RD proved very promising therapeutic activity also in human FaDu xenografts and negligible toxicity predetermining these nanomedicines as side-effect free nanosystem. The therapeutic potential could be highly increased using the fine-tuned combination with other drugs, i.e. doxorubicin, attached to the same polymer system. Finally, we summarize that described polymer nanomedicines fulfilled all the requirements as potential candidates for deep preclinical investigation.

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The absorption and release of 6-mercaptopurine anticancer drug was investigated in biodegradable and biocompatible polymer of polylactic acid (PLA) using molecular dynamics simulation. For this purpose, the amount of mixing energy, radius of gyration, mean squared displacement and radial distribution function were computed and compared in concentrations of 5-36 wt% of 6-mercaptopurine drug. The simulation results show that increasing the concentration of the drug reduces mixing energy and PLA polymer carrier is able to carry 35.8 wt% of 6-mercaptopurine anticancer drug. Based on these results, the amount of 6-mercaptopurine release from PLA carrier 35.8 wt% of it in water environment is zero due to hydrophobic property of PLA and 6-mercaptopurine. Finally, polyethylene glycol (PEG) polymer with different percentages (10-30 wt%) was used to modify PLA carrier. The simulation results show that the rate of drug release increases by increasing the concentration of PEG polymer in the modified PLA carrier and also with increasing the percentage of drug loaded in the carrier and also the optimum weight percentage of PEG in modified PLA carrier for 35.8 wt% of drug concentration is 11 wt% and the rate of drug release is slower and equal to 4.4 molecules/ns.

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Metallodendrimers-dendrimers with included metals-are widely investigated as biocompatible equivalents to metal nanoparticles. Applications can be expected in the fields of catalysis, as chemical sensors in molecular recognition and as anticancer drugs. Metallodendrimers can also mimic certain biomolecules, for example, haemoprotein in the case of using a dendrimer with a porphyrin core. In previous papers, we showed the promising anticancer effects of carbosilane ruthenium dendrimers. The present paper is devoted to studying biocompatibility and the cytotoxic effect on normal and cancer cells of carbosilane ruthenium dendrimers labelled with fluorescent probe fluorescein isothiocyanate (FITC). The addition of fluorescent probe allowed tracking the metallodendrimer in both normal and cancer cells. It was found that carbosilane ruthenium dendrimer labelled with FITC in concentration up to 10 µmol/L was more cytotoxic for cancer cells than for normal cells. Thus, FITC labelled carbosilane ruthenium dendrimer is a good candidate for diagnostic imaging and studying anticancer effects of metallodendrimers in cancer therapy.

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Marine resources are well recognized for their biologically active substances with great potential applications in the cosmeceutical industry. Among the different compounds with a marine origin, chitin and its deacetylated derivative-chitosan-are of great interest to the cosmeceutical industry due to their unique biological and technological properties. In this review, we explore the different functional roles of chitosan as a skin care and hair care ingredient, as an oral hygiene agent and as a carrier for active compounds, among others. The importance of the physico-chemical properties of the polymer in its use in cosmetics are particularly highlighted. Moreover, we analyse the market perspectives of this polymer and the presence in the market of chitosan-based products.

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AIM: The capability of reducing fibrotic and inflammatory responses in lung tissues represents a gold standard for evaluating the efficacy of therapeutic interventions for treating idiopathic pulmonary fibrosis (IPF). A wide variety of therapeutic strategies have been employed in clinic to treat PF, but limited success has been obtained. Apigenin (4, 5, 7-trihydroxyflavone) is a member of flavonoid family that exerts anti-inflammatory and anti-fibrosis effects. In this study, we explore the potential therapeutic effect of apigenin in lung fibrosis. MATERIALS AND METHODS: Apigenin was employed to treat IPF in a bleomycin-induced PF rat model. Apigenin was loaded onto a biodegradable polymer carrier (nanoparticle, NP) to improve its bio-solubility and bio-availability. The properties (e.g. size, apigenin loading and release profile) of the apigenin loaded polymer carrier were well-characterized. In vitro study was performed to assess the impact of apigenin on pulmonary cell viability, growth, as well as inflammatory and pro-fibrosis responses in pulmonary cells. The impact of apigenin on the production of inflammatory cytokines (e.g. TGF-ß, TNF-α) and pro-fibrosis factors in bronchoalveolar lavage fluid and pulmonary cells from lung tissues was also investigated. RESULTS: Our results showed, apigenin has anti-fibrosis effect by inhibition fibrosis related cytokines expression. And compared with apigenin in soluble form, the strategic release of apigenin is more effective in inhibiting pulmonary fibrosis and inflammation. CONCLUSION: Our finding suggested that apigenin loaded on polymeric carrier might be an effective treatment for pulmonary fibrosis patients.

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OBJECTIVE: The aim of this study was to evaluate the effect of polymer carrier, hot melt extrusion and downstream processing parameters on the water uptake properties of amorphous solid dispersions. METHODS: Three polymers and a model drug were used to prepare amorphous solid dispersions utilizing the hot melt extrusion technology. The sorption-desorption isotherms of solid dispersions and their physical mixtures were measured by the dynamic vapour sorption system, and the effects of polymer hydrophobicity, hygroscopicity, molecular weight and the hot melt extrusion process were investigated. Fourier transform infrared (FTIR) imaging was performed to understand the phase separation driven by the moisture. KEY FINDINGS: Solid dispersions with polymeric carriers with lower hydrophilicity, hygroscopicity and higher molecular weight could sorb less moisture under the high relative humidity (RH) conditions. The water uptake ability of polymer-drug solid dispersion systems were decreased compared with the physical mixture after hot melt extrusion, which might be due to the decreased surface area and porosity. The FTIR imaging indicated that the homogeneity of the drug molecularly dispersed within the polymer matrix was changed after exposure to high RH. CONCLUSION: Understanding the effect of formulation and processing on the moisture sorption properties of solid dispersions is essential for the development of drug products with desired physical and chemical stability.

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In order to study the liver targeting of the N-galactosylated chitosan (GC) polymer in liver, we first conjugated the lactobionic acid with chitosan (CS) to obtain the carrier of GC with different degree of substitution of lactosyl group. Western blot was performed to detect the expression levels of the asialoglycoprotein receptors (ASGPR) in the cell lines of HepG2, SMMC-7721, and HL-7702. The protein level of ASGPR was lower in HepG2 compared to HL-7702 and SMMC-7721. Although all treated by CS, viabilities of HL-7702 and HepG2 did not experience any significant drop, while viability of SMMC-7721 decreased 15% on average from control. It was the first data about the inhibitory effect of GC on the liver cells. Fluorescein isothiocyanate (FITC) labeled GC (GC-FITC) was injected intravenously into mice at a dose of 0.02 µmol/mouse. GC-FITC showed maximum liver localization at 5 min and even detectable at 48 h after injection. Further, the accumulation of GC in liver was about 5.4-fold higher than that of CS. In conclusion, GC demonstrated its higher efficacy in drug liver targeting and thus could be a more promising drug or gene carrier in future therapies.

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