Protein release from nanocellulose and alginate hydrogels: The study of adsorption and desorption kinetics.

This work presents a study of the lysozyme release from crosslinked TEMPO nanocellulose (TOCNF) and alginate (ALG) hydrogels in a medium with different ionic strength and temperature. The main objective is to develop a mathematical model for a detailed study of the concurrent action of diffusion mechanism and adsorption/desorption kinetics. Model fit parameters provide important information about the initial (maximum) adsorption rate and its deceleration with increasing ionic strength of the release medium. Similarly, the initial (minimum) desorption rate and its acceleration with increasing salt concentration can be determined. The model leads us to the conclusion that the initial adsorption rate is higher in the case of TOCNF, but due to fewer electrostatic interactions and morphology as well as topography of the surface, it decreases to a negligible value much faster than in the case of ALG, where the diffusion process becomes dominant.

Effect of polymer-polymer interactions on the flow behavior of some polysaccharide-based hydrogel blends.

This study is the continuation of our previous work (Kopac, Abrami, et al., 2021) where the theoretical approach of polymer-polymer interaction to predict the crosslink density of hydrogels was introduced. This theory is further extended to the flow properties of hydrogels that allow the analysis of synergistic effect in hydrogel systems and the understanding of possible anomalous behavior of certain mixtures. Various hydrogel structures were prepared accordingly by blending scleroglucan, anionic nanocellulose, Laponite dispersions and alginate solution. The relationship between mechanical and flow properties of the hydrogel network was carefully studied and eventually described by mathematical model. The linear model equation to predict yield stress of hydrogels in relation to the crosslink density was designed showing a satisfactory agreement between experimental data and model predictions. The correlation was adjusted by defining a proportionality coefficient, representing the energy defined per moles of crosslinks that can be used to restore the deformation.

Polysaccharide-based hydrogels crosslink density equation: A rheological and LF-NMR study of polymer-polymer interactions.

A simple relation between pendant groups of polymers in hydrogels is introduced to determine the crosslink density of (complex) hydrogel systems (mixtures of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) modified nanocellulose, alginate, scleroglucan and Laponite in addition of crosslinking agents). Furthermore, the rheological properties and their great potential connection to design complex hydrogel systems with desired properties have been thoroughly investigated. Hydrogel structures governing internal friction and flow resistance were described by the predominant effect of ionic, hydrogen, and electrostatic interactions. The relationship between rheological properties and polymer-polymer interactions in the hydrogel network is explained and expressed in a new mathematical model for determining the crosslink density of (crosslinked) hydrogels based on single or mixture of polymer systems. In the end, the combined used of rheology and low field nuclear magnetic resonance spectroscopy (LF-NMR) for the characterization of hydrogel networks is developed.

Bacteriophage Delivery Systems Based on Composite PolyHIPE/Nanocellulose Hydrogel Particles.

The role of bacteriophage therapy in medicine has recently regained an important place. Oral phage delivery for gastrointestinal treatment, transport through the stomach, and fast release in the duodenum is one of such applications. In this work, an efficient polyHIPE/hydrogel system for targeted delivery of bacteriophages with rapid release at the target site is presented. T7 bacteriophages were encapsulated in low crosslinked anionic nanocellulose-based hydrogels, which successfully protected phages at pH < 3.9 (stomach) and completely lost the hydrogel network at a pH above 3.9 (duodenum), allowing their release. Hydrogels with entrapped phages were crosslinked within highly porous spherical polyHIPE particles with an average diameter of 24 µm. PolyHIPE scaffold protects the hydrogels from mechanical stimuli during transport, preventing the collapse of the hydrogel structure and the unwanted phage release. On the other hand, small particle size, due to the large surface-to-volume ratio, enables rapid release at the target site. As a consequence, a fast zero-order release was achieved, providing improved patient compliance and reduced frequency of drug administration. The proposed system therefore exhibits significant potential for a targeted drug delivery in medicine and pharmacy.

A mathematical model for pH-responsive ionically crosslinked TEMPO nanocellulose hydrogel design in drug delivery systems.

Ionically crosslinked hydrogels based on TEMPO nanocelullose and alginate were prepared to develop a generalized pH value, temperature and biopolymer concentration dependent mathematical model. The distinctive attention was in the demonstration of hydrogen bonds effects in the mathematical model, prevailing especially in the field of low crosslink densities of TEMPO nanocellulose hydrogel in acid medium. Accordingly, alginate hydrogels were subjected to the research as comparable samples with less significant hydrogel bonds effect. The equation was built upon the determination of the average mesh size in a TEMPO nanocellulose and alginate hydrogel network and studying its changes in different pH release environments. Based on rheological measurements of TEMPO nanocellulose and alginate from the basic and acidic release environment, the mechanism of swelling and shrinkage was thoroughly discussed as well as the influence of substituent groups, ionic interactions and hydrogen bonds in different pH medium were evaluated. Due to the protonation of carboxylic groups, TEMPO nanocellulose and alginate hydrogels shrink in an acid environment. The presented approach will accelerate, improve and reduce the cost of research in the field of controlled release technology with target drug delivery.

The mutual effect of the crosslinker and biopolymer concentration on the desired hydrogel properties.

Controlled release technology has a great potential in pharmaceutical and medical applications to ensure high efficacy of treatment, reduces the aggressive action of the medicines per patient, decreases the cost of treatment and reduces the side effects of the drug as well. In this research, hydrogels from biopolymers were designed for potential use in the drug release systems. The main objective was the manipulation of alginate and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) - oxidized cellulose nanofibers hydrogels crosslinking density by changing the biopolymer and crosslinker concentrations. Rheological measurements of prepared hydrogels were performed to determine the viscosity as a biomedical applicability factor and for determining shear modulus as a basis for theoretical mesh size calculations. The homogeneity of the hydrogel was confirmed by NMR verifying the validity of the mesh size calculations at the same time. In the last stage, the improved mathematical model was developed taking into account the concentration of crosslinker and the concentration of biopolymer in hydrogel as well. The designed model is the first step for the preparation of hydrogels with specific properties.

The use of ultrasound in the crystallization process of an active pharmaceutical ingredient.

In this research, ultrasound was used in the crystallization process as an alternative to conventional spontaneous crystallization and seeding crystallization. The study was implemented on an active pharmaceutical ingredient ticagrelor, where the influence of ultrasound on its physical properties was evaluated. Process parameters of spontaneous crystallization, seeding crystallization and ultrasound-assisted crystallization were extensively studied while the pros and cons of each were adequately exposed. Compared to spontaneous crystallization and seeding crystallization ultrasound-assisted crystallization has significantly improved fundamental crystallization parameters: nucleation, the growth of crystals and filtration time. At the same time, the tendency of particles to agglomerate was reduced, which lead to the avoidance of energy and time-consuming process of final product deagglomeration, often problematic in conventional crystallization. In addition, different physical properties of ticagrelor were reached and evaluated, for instance, morphology, particle size distribution and different polymorphic forms. Polymorphic forms I, II and III were efficiently produced in a repeatable, robust and optimal way. Ultrasound-assisted crystallization was proved to have a beneficial effect on the crystallization process of API, even on the industrial scale, and can successfully replace spontaneous crystallization and seeding crystallization.

Chemical and chromatographic stability of methacrylate-based monolithic columns.

Chemical and chromatographic stability of methacrylate-based monolithic columns bearing 3-N,N-diethylamino-2-hydroxypropyl (DEAE) and quarternary amine (QA) groups was studied. The leakage products from both monolithic columns were determined and the leakage of amines has been quantified in alkali solutions. Monolithic columns bearing QA functional groups being exposed to 1M sodium hydroxide solution for up to 3 months caused reduction of ion-exchange groups for approximately 12%, while for DEAE monolithic columns was only around 3% in 1 year. In 0.1M NaOH and 20% ethanol degradation was significantly lower. The main leaking compound from DEAE monolith was found to be 3-(diethylamino)-1,2-propanediol and 2,3-dihydroxypropyltrimethylammonium salt for QA monolith. During repeated 50 cleaning-in-place (CIP) cycles, no changes in chromatographic properties were detected.