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Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 169
Author(s):  
Javier Pérez Quiñones ◽  
Cornelia Roschger ◽  
Aitziber Iturmendi ◽  
Helena Henke ◽  
Andreas Zierer ◽  
...  

The design and study of efficient polymer-based drug delivery systems for the controlled release of anticancer drugs is one of the pillars of nanomedicine. The fight against metastatic and invasive cancers demands therapeutic candidates with increased and selective toxicity towards malignant cells, long-term activity and reduced side effects. In this sense, polyphosphazene nanocarriers were synthesized for the sustained release of the anticancer drugs camptothecin (CPT) and epirubicin (EPI). Linear poly(dichloro)phosphazene was modified with lipophilic tocopherol or testosterone glycinate, with antioxidant and antitumor activity, and with hydrophilic Jeffamine M1000 to obtain different polyphosphazene nanocarriers. It allowed us to encapsulate the lipophilic CPT and the more hydrophilic EPI. The encapsulation process was carried out via solvent exchange/precipitation, attaining a 9.2–13.6 wt% of CPT and 0.3–2.4 wt% of EPI. CPT-loaded polyphosphazenes formed 140–200 nm aggregates in simulated body physiological conditions (PBS, pH 7.4), resulting in an 80–100-fold increase of CPT solubility. EPI-loaded polyphosphazenes formed 250 nm aggregates in an aqueous medium. CPT and EPI release (PBS, pH 7.4, 37 °C) was monitored for 202 h, being almost linear during the first 8 h. The slow release of testosterone and tocopherol was also sustained for 150 hours in PBS (pH 7.4 and 6.0) at 37 °C. The co-delivery of testosterone or tocopherol and the anticancer drugs from the nanocarriers was expected. Cells of the human breast cancer cell line MCF-7 demonstrated good uptake of anticancer-drug-loaded nanocarriers after 6 hours. Similarly, MCF-7 spheroids showed good uptake of the anticancer-drug-loaded aggregates after 72 hours. Almost all anticancer-drug-loaded polyphosphazenes exhibited similar or superior toxicity against MCF-7 cells and spheroids when compared to raw anticancer drugs. Additionally, cell-cycle arrest in the G2/M phase was increased in response to the drug-loaded nanocarriers. Almost no toxicity of anticancer-drug-loaded aggregates against primary human lung fibroblasts was observed. Furthermore, the aggregates displayed no hemolytic activity, which is in contrast to the parent anticancer drugs. Consequently, synthesized polyphosphazene-based nanocarriers might be potential nanomedicines for chemotherapy.


Polymers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 28
Author(s):  
Evgeniya V. Talalaeva ◽  
Aleksandra A. Kalinina ◽  
Evgeniy V. Chernov ◽  
Alina G. Khmelnitskaia ◽  
Marina A. Obrezkova ◽  
...  

This paper reports a method for the synthesis of 1,1,3,3,5,5-hexamethyl-7,7-diorganocyclotetrasiloxanes by the interaction of 1,5-disodiumoxyhexamethylsiloxane with dichlorodiorganosilanes such as methyl-, methylvinyl-, methylphenyl-, diphenyl- and diethyl dichlorosilanes. Depending on the reaction conditions, the preparative yield of the target cyclotetrasiloxanes is 55–75%. Along with mixed cyclotetrasiloxanes, the proposed method leads to the formation of polymers with regular alternation of diorganosylil and dimethylsylil units. For example, in the case of dichlorodiethylsilane, 70% content of linear poly(diethyl)dimethylsiloxanes with regular alternation of units can be achieved in the reaction product. Using 7,7-diethyl-1,1,3,3,5,5-hexamethylcyclotetrasiloxane as an example, the prospects of the mixed cycle in copolymer preparation in comparison with the copolymerization of octamethyl- and octaethylcyclotetrasiloxanes are shown.


2021 ◽  
Author(s):  
Qing Yu ◽  
Richard England ◽  
Anders Gunnarsson ◽  
Robert Luxenhofer ◽  
Kevin Treacher ◽  
...  

Polymeric micelles have been extensively used as nanocarriers for the delivery of chemotherapeutic agents aiming to improve their efficacy in cancer treatment. However, poor loading capacity, premature drug release, non-uniformity and reproducibility still remain the major challenges. To create a stable polymeric micelle with high drug loading, a telodendrimer micelle was developed as a nanocarrier for fulvestrant, as an example of a drug that has extremely poor water solubility (sub nanomolar range). Telodendrimers were prepared by synthesis of a hydrophilic linear poly(sarcosine) and growing a lysine dendron from the chain terminal amine by a divergent synthesis. At the periphery of the dendritic block, 4, 8, and 16 fulvestrant molecules were conjugated to the lysine dendron creating a hydrophobic block. Having drug as part of the carrier not only reduces the usage of the inert carrier materials but also prevent the drugs from leakage and premature release by diffusion. The self-assembled telodendrimer micelles demonstrated good colloidal stability (CMC < 2 µM) in buffer and were uniform in size. In addition, these telodendrimer micelles could solubilize additional fulvestrant yielding an excellent overall drug loading capacity of up to 77 wt.% total drug load (summation of conjugated and encapsulated). Importantly, the size of the micelles could be tuned between 25-150 nm by controlling (i) the ratio between hydrophilic and hydrophobic blocks and (ii) the amount of encapsulated fulvestrant. The versatility of these telodendrimer-based micelle systems to both conjugate and encapsulate drug with high efficiency and stability, in addition to possessing other tuneable properties makes it a promising drug delivery system for a range of active pharmaceutical ingredients and therapeutic targets.


2021 ◽  
Vol 2132 (1) ◽  
pp. 012026
Author(s):  
Liping Liu ◽  
Liucheng Jiang ◽  
Lele Qiao

Abstract Recent studies on the test of ceramic non-destructive testing are mainly based on high cost technologies, image processing and so on, these method possesses some drawback of low efficiency, high cost and so on. What’s more, detecting whether the ceramic products by human through listening to sound of tapping is also effectless. This paper proposed a non-destructive method for ceramic products to solve this problem. This non-destructive method consists of a tapping device and a signal processing module. The tapping device will be applied to generate the tapping sound signal and the signal processing system will be applied to analysis signal. After the process of signal analysis, sample length and peak of spectrum 2 parameters is extracted, then use these parameters to train SVM, the results will be compared with BP neural network (BPNN). The result of experiment shows that SVM with different kernels of linear, poly, rbf, sigmoid respectively reach the accuracy of 96.29%, 96.29%, 46.29%, 93.82%, while BPNN reaches the accuracy of 93.21%. This result proves that SVM can effectively complete the task of identifying defective ceramics, and its performance is better than BPNN.


2021 ◽  
Vol 22 (22) ◽  
pp. 12265
Author(s):  
Elena Tarabukina ◽  
Emil Fatullaev ◽  
Anna Krasova ◽  
Maria Sokolova ◽  
Mikhail Kurlykin ◽  
...  

A new polycondensation aromatic rigid-chain polyester macroinitiator was synthesized and used to graft linear poly-2-ethyl-2-oxazoline as well as poly-2-isopropyl-2-oxazoline by cationic polymerization. The prepared copolymers and the macroinitiator were characterized by NMR, GPC, AFM, turbidimetry, static, and dynamic light scattering. The molar masses of the polyester main chain and the grafted copolymers with poly-2-ethyl-2-oxazoline and poly-2-isopropyl-2-oxazoline side chains were 26,500, 208,000, and 67,900, respectively. The molar masses of the side chains of poly-2-ethyl-2-oxazoline and poly-2-isopropyl-2-oxazoline and their grafting densities were 7400 and 3400 and 0.53 and 0.27, respectively. In chloroform, the copolymers conformation can be considered as a cylinder wormlike chain, the diameter of which depends on the side chain length. In water at low temperatures, the macromolecules of the poly-2-ethyl-2-oxazoline copolymer assume a wormlike conformation because their backbones are well shielded by side chains, whereas the copolymer with short side chains and low grafting density strongly aggregates, which was visualized by AFM. The phase separation temperatures of the copolymers were lower than those of linear analogs of the side chains and decreased with the concentration for both samples. The LCST were estimated to be around 45 °C for the poly-2-ethyl-2-oxazoline graft copolymer, and below 20 °C for the poly-2-isopropyl-2-oxazoline graft copolymer.


Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6601
Author(s):  
Joanna Bojda ◽  
Ewa Piorkowska ◽  
Grzegorz Lapienis ◽  
Adam Michalski

The influence of macromolecular architecture on shear-induced crystallization of poly(L-lactide) (PLLA) was studied. To this aim, three star PLLAs, 6-arm with Mw of 120 and 245 kg/mol, 4-arm with Mw of 123 kg/mol, and three linear PLLAs with Mw of 121, 240 and 339 kg/mol, were synthesized and examined. The PLLAs were sheared at 170 and 150 °C, at 5/s, 10/s and 20/s for 20 s, 10 s and 5 s, respectively, and then cooled at 10 or 30 °C/min. Shear-induced crystallization during cooling was followed by a light depolarization method, whereas the crystallized specimens were examined by DSC, 2D-WAXS, 2D-SAXS and SEM. The effect of shear depended on the shearing conditions, cooling rate and polymer molar mass but it was also affected by the macromolecular architecture. The shear-induced crystallization of linear PLLA with Mw of 240 kg/mol was more intense than that of the 6-arm polymer with similar Mw, most possibly due to its higher Mz. However, the influence of shear on the crystallization of the star polymers with Mw close to 120 kg/mol was stronger than on that of their linear analog. This was reflected in higher crystallization temperature, as well as crystallinity achieved during cooling.


Polymers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 3560
Author(s):  
Zina Vuluga ◽  
Catalina-Gabriela Sanporean ◽  
Denis Mihaela Panaitescu ◽  
George Mihail Teodorescu ◽  
Mihai Cosmin Corobea ◽  
...  

Masterbatches from a linear poly[styrene-b-(ethylene-co-butylene)-b-styrene] (SEBS) and halloysite nanotubes (HNT-QM) were obtained in different conditions of temperature and shear using two co-rotating twin-screw extruders. The influence of screw configuration and melt processing conditions on the morpho-structural, thermal and mechanical properties of masterbatches at macro and nanoscale was studied. A good dispersion of halloysite nanotubes and better thermal stability and tensile and nanomechanical properties were obtained at a lower temperature profile and higher screw speed. The effect of masterbatches, the best and worst alternatives, on the properties of a polypropylene (PP)–glass fiber (GF) composite was also evaluated. Double hardness, tensile strength and modulus and four times higher impact strength were obtained for PP/GF composites containing masterbatches compared to pristine PP. However, the masterbatch with the best properties led further to enhanced mechanical properties of the PP/GF composite. A clear difference between the effects of the two masterbatches was obtained by nanoindentation and nanoscratch tests. These analyses proved to be useful for the design of polymer composites for automotive parts, such as bumpers or door panels. This study demonstrated that setting-up the correct processing conditions is very important to obtain the desired properties for automotive applications.


2021 ◽  
Vol 52 ◽  
pp. 101702
Author(s):  
Nanhua Wu ◽  
Yifeng Zou ◽  
Rong Xu ◽  
Jing Zhong ◽  
Jing Li

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