In situ Formation of Polymer Microparticles in Bacterial Nanocellulose Using Alternative and Sustainable Solvents to Incorporate Lipophilic Drugs

Bacterial nanocellulose has been widely investigated in drug delivery, but the incorporation of lipophilic drugs and controlling release kinetics still remain a challenge. The inclusion of polymer particles to encapsulate drugs could address both problems but is reported sparely. In the present study, a formulation approach based on in situ precipitation of poly(lactic-co-glycolic acid) within bacterial nanocellulose was developed using and comparing the conventional solvent N -methyl-2-pyrrolidone and the alternative solvents poly(ethylene glycol), Cyrene TM and ethyl lactate. Using the best-performing solvents N -methyl-2-pyrrolidone and ethyl lactate, their fast diffusion during phase inversion led to the formation of homogenously distributed polymer microparticles with average diameters between 2.0 and 6.6 µm within the cellulose matrix. Despite polymer inclusion, the water absorption value of the material still remained at ~50% of the original value and the material was able to release 32 g/100 cm 2 of the bound water. Mechanical characteristics were not impaired compared to the native material. The process was suitable for encapsulating the highly lipophilic drugs cannabidiol and 3-O-acetyl-11-keto-β-boswellic acid and enabled their sustained release with zero order kinetics over up to 10 days. Conclusively, controlled drug release for highly lipophilic compounds within bacterial nanocellulose could be achieved using sustainable solvents for preparation

Incorporation of indole significantly improves the transfection efficiency of guanidinium‐containing poly(methacrylamide)s

Abstract A highly efficient transfection agent is reported that is based on terpolymer consisting of N ‐(2‐hydroxypropyl)methacrylamide (HPMA), N ‐(3‐guanidinopropyl) methacrylamide (GPMA), and N ‐(2‐indolethyl)methacrylamide monomers (IEMA) by analogy to the amphipathic cell‐penetrating peptides containing tryptophan and arginine residues. The incorporation of the indole‐bearing monomer leads to successful plasmid DNA condensation even at a nitrogen‐to‐phosphate (N/P) ratio of 1. The hydrodynamic diameter of polyplexes is determined to be below 200 nm for all N/P ratios. The transfection studies demonstrate a 200‐fold increase of the transgene expression in comparison to P(HPMA‐co‐GPMA) with the same guanidinium content. This study reveals the strong potential of the indole group as a side‐chain pendant group that can increase the cellular uptake of polymers and the transfection efficiency of the respective polyplexes

Indole, phenyl, and phenol Groups: The role of the comonomer on gene delivery in guanidinium containing methacrylamide terpolymers

Abstract This report highlights the importance of hydrophobic groups mimicking the side chains of aromatic amino acids, which are tryptophan, phenylalanine, and tyrosine, in guanidinium bearing poly(methacrylamide)s for the design of non‐viral gene delivery agents. Guanidinium containing methacrylamide terpolymers are prepared by aqueous reversible addition–fragmentation chain transfer ( a RAFT) polymerization with different hydrophobic monomers, N ‐(2‐indolethyl)methacrylamide (IEMA), N ‐phenethylmethacrylamide (PhEMA), or N ‐(4‐hydroxyphenethyl)methacrylamide (PhOHEMA) by aiming similar contents. The well‐defined polymers are obtained with a molar mass of ≈15 000 g mol −1 and ≈1.1 dispersity. All terpolymers demonstrate almost comparable in vitro cell viability and hemocompatibility profiles independent of the type of side chain. Although they all form positively charged, enzymatically stable polyplexes with plasmid DNA smaller than 200 nm, the incorporation of the IEMA monomer improve these parameters by demonstrating a higher DNA binding affinity and forming nanoassemblies of about 100 nm. These physicochemical characteristics are correlated with increased transfection rates in CHO‐K1 cells dependent on the type of the monomer and the nitrogen to phosphate (N/P) ratio of the polyplexes, as determined by luciferase reporter gene assays

The Influence of Various Factors on the Progress in Training of International Learners of the Preparatory Department (on the Example of the Course "Computer Science")

The task of research different factors affecting on the progress in training of students is actual. Two main factors as training the course in native language and knowledge of the language in which the course is studied were considered to solve this problem. The research is aimed at learners of the Preparatory Department studying in a non-native language (Russian) and takes into account the characteristics of such contingent of students. The study was made in the course "Computer science" with the help of methods of mathematical statistics. This research was conducted to improve the methods and to change the approaches in teaching the pre-university programs

Characterisation of the passive permeability barrier of nuclear pore complexes

Nuclear pore complexes (NPCs) restrict uncontrolled nucleocytoplasmic fluxes of inert macromolecules but permit facilitated translocation of nuclear transport receptors and their cargo complexes. We probed the passive barrier of NPCs and observed sieve-like properties with a dominating mesh or channel radius of 2.6 nm, which is narrower than proposed earlier. A small fraction of diffusion channels has a wider opening, explaining the very slow passage of larger molecules. The observed dominant passive diameter approximates the distance of adjacent hydrophobic clusters of FG repeats, supporting the model that the barrier is made of FG repeat domains cross-linked with a spacing of an FG repeat unit length. Wheat germ agglutinin and the dominant-negative importin β45-462 fragment were previously regarded as selective inhibitors of facilitated NPC passage. We now observed that they do not distinguish between the passive and the facilitated mode. Instead, their inhibitory effect correlates with the size of the NPC-passing molecule. They have little effect on small species, inhibit the passage of green fluorescent protein-sized objects >10-fold and virtually block the translocation of larger ones. This suggests that passive and facilitated NPC passage proceed through one and the same permeability barrier