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This paper describes the synthesis and characterization of new bivalent folate-targeted PEGylated doxorubicin (FA2-dPEG-DOX2) made by modular chemo-enzymatic processes using Candida antarctica lipase B (CALB) as a biocatalyst. Unique features are the use of monodisperse PEG (dPEG) and the synthesis of thiol-functionalized folic acid yielding exclusive γ-conjugation of folic acid (FA) to dPEG. The polymer-based drug conjugate is built up by a series of transesterification and Michael addition reactions all catalyzed be CALB. In comparison with other methods in the literature, the modular approach with enzyme catalysis leads to selectivity, full conversion and high yield, and no transition metal catalyst residues. The intermediate product with four acrylate groups is an excellent platform for Michael-addition-type reactions for a wide variety of biologically active molecules. The chemical structures were confirmed by nuclear magnetic resonance spectroscopy (NMR). Flow cytometry analysis showed that, at 10 µM concentration, both free DOX and FA2-dPEG-DOX2 were taken up by 99.9% of triple-negative breast cancer cells in 2 h. Fluorescence was detected for 5 days after injecting compound IV into mice. Preliminary results showed that intra-tumoral injection seemed to delay tumor growth more than intravenous delivery.

This paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA2-dPEG-DOX2). A unique feature is the use of monodisperse PEG (dPEG). The modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues. Flow cytometry analysis showed that at 10 µM concentration, both free DOX and FA2-dPEG-DOX2 would be taken up by 99.9% of triple-negative breast cancer cells in 2 h. Intratumoral injection to mice seemed to delay tumor growth more than intravenous delivery. The mouse health status, food, water consumption, and behavior remained unchanged during the observation.

This paper presents the results of the first part of testing a novel electrospun fiber mat based on a unique macromolecule: polyisobutylene (PIB). A PIB-based compound containing zinc oxide (ZnO) was electrospun into self-supporting mats of 203.75 and 295.5 g/m2 that were investigated using a variety of techniques. The results show that the hydrophobic mats are not cytotoxic, resist fibroblast cell adhesion and biofilm formation and are comfortable and easy to breathe through for use as a mask. The mats show great promise for personal protective equipment and other applications.

This paper investigates liquid chromatography at critical condition (LCCC) for polymer analysis. Based on controversial claims on the separation of cyclic polymers from linear analogues in the literature, the efficiency of LCCC for separation and purity analysis is questioned. Polyisobutylene (PIB) and poly(3,6-dioxa-1,8-octanedithiols) (polyDODT) were used for the study. The structure of low molecular weight cyclic and linear polyDODT was demonstrated by MALDI-ToF. NMR did not show the presence of thiol end groups in higher molecular weight PIB-disulfide and polyDODT samples, so they were considered cyclic polymers. When a low molecular weight polyDODT oligomer with only traces of cycles, as demonstrated by MALDI-ToF, was mixed with an M_n = 27 K g/mol cyclic sample, LCCC did not detect the presence of linear oligomers at 6 wt%. Based on the data presented here, it can be concluded that the LCCC method is not capable of measuring

This study investigated cell viability in the presence of allylamine-modified and plasma-treated electrospun polysuccinimide fiber mats (PSI-AAmp). Low pressure non-equilibrium plasma was used for crosslinking the PSI-AAm. Comparison of FTIR and XPS analyses demonstrated that crosslinking occurred on the surface of the samples. Cell viability was investigated using the MG-63 osteosarcoma cell line and WST-1 viability reagent. Since PSI hydrolyzes to poly(aspartic acid) (PASP), PASP was used in addition to the regular controls (cells only). Phase contrast showed normal morphology in all cases at 24 h, however, in the presence of PSI-AAmp at 72 h, some rounded, dead cells could also be seen, and proliferation was inhibited. Since proliferation in the presence of PASP alone was not inhibited, the cause of inhibition was not the final product of the hydrolysis. Further investigations will be carried out to pinpoint the cause.

This paper focuses on reviewing recent developments in folate-targeted cancer diagnostic agents. First clinical trials involving Small Molecule Diagnostic Conjugates (SMDCs) are discussed, followed by Polymer-based Folate-targeted Diagnostic Conjugates (PDCs). Specifically, the advantages of multivalent targeting are discussed. Finally, recent results of a new chemo-enzymatic approach for the synthesis of bivalent folate targeted, PEGylated PDCs is discussed. Unique feature is the use of monodisperse PEG (dPEG). This modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues.

Electrospinning is a versatile method for the preparation of polymer fiber networks. From the medical application point of view, the stability of the fibrous structure in water is crucial. The aim of this research was to explore the possibility to induce crosslinking by treatment with non-equilibrium low pressure plasma to give structural stability to fibrous meshes. Low pressure plasma treatment was studied to induce crosslinking in allylamine-modified polysuccinimide nanofibers. Polysuccinimide was first modified with allylamine (PSI-AA) to attach the reactive allyl groups to the polymer chain. Allylamine-modification degrees varied between 10 and 100%. Then PSI-AA meshes were created by electrospinning followed by low pressure plasma treatment to allow the allylamine groups to establish crosslinks in the meshes. The crosslinked structure was confirmed by immersing both the plasma-treated, and untreated PSI-AA meshes in dimethyl sulfoxide, which is a good solvent of the non-crosslinked PSI-AA. Plasma-treated meshes kept their integrity, while the untreated samples dissolved almost immediately, which proved the formation of crosslinks due to plasma treatment. Structural changes in the meshes were studied with infrared spectroscopy (IR). X-ray photoelectron spectroscopy (XPS) investigates the structural changes on the surface of the samples and proved the presence of crosslinks. PSI-AA meshes were then hydrolyzed into poly(aspartic acid) (PASP) meshes and with the right choice of synthesis parameters (allylamine grafting degree, plasma treatment duration and power) PASP hydrogel meshes retained their fibrous structure, which was observed in SEM images of PSI-AA meshes.