Hydrogel materials with a gel-sol conversion due to external environmental changes have potential applications in a wide range of fields, including controlled drug delivery. Succinoglycans are anionic extracellular polysaccharides produced by various bacteria, including Sinorhizobium species, which have diverse applications. In this study, the rheological analysis confirmed that succinoglycan produced by Sinorhizobium meliloti Rm 1021 binds weakly to various metal ions, including Fe²⁺ cations, to maintain a sol form, and binds strongly to Fe³⁺ cations to maintain a gel form. The Fe³⁺-coordinated succinoglycan (Fe³⁺-SG) hydrogel was analyzed by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, circular dichroism (CD), and field-emission scanning electron microscopy (FE-SEM). Our results revealed that the Fe³⁺ cations that coordinated with succinoglycan were converted to Fe²⁺ by a reducing agent and visible light, promoting a gel-sol conversion. The Fe³⁺-SG hydrogel was then successfully used for controlled drug delivery based on gel-sol conversion in the presence of reducing agents and visible light. As succinoglycan is nontoxic, it is a potential material for controlled drug delivery. Full article

The effect of a range of synthetic charged polymers on alpha-synuclein aggregation and amyloid formation was tested. Sulfated aromatic polymers, poly(styrene sulfonate) and poly(anethole sulfonate), have been found to suppress the fibril formation. In this case, small soluble complexes, which do not bind with thioflavin T, have been formed in contrast to the large stick-type fibrils of free alpha-synuclein. Sulfated polysaccharide (dextran sulfate), as well as sulfated vinylic polymer (poly(vinyl sulfate)) and polycarboxylate (poly(methacrylic acid)), enhanced amyloid aggregation. Conversely, pyridinium polycation, poly(N-ethylvinylpyridinium), switched the mechanism of alpha-synuclein aggregation from amyloidogenic to amorphous, which resulted in the formation of large amorphous aggregates that do not bind with thioflavin T. The obtained results are relevant as a model of charged macromolecules influence on amyloidosis development in humans. In addition, these results may be helpful in searching for new approaches for synucleinopathies treatment with the use of natural polymers. Full article

Hydrogels are excellent candidates for the sustained local delivery of anticancer drugs, as they possess tunable physicochemical characteristics that enable to control drug release kinetics and potentially tackle the problem of systemic side effects in traditional chemotherapeutic delivery. Yet, current systems often involve complicated manufacturing or covalent bonding processes that are not compatible with regulatory or market reality. Here, we developed a novel gelatin methacryloyl (GelMA)-based drug delivery system (GelMA-DDS) for the sustained local delivery of paclitaxel-based Abraxane^®, for the prevention of local breast cancer recurrence following mastectomy. GelMA-DDS readily encapsulated Abraxane^® with a maximum of 96% encapsulation efficiency. The mechanical properties of the hydrogel system were not affected by drug loading. Tuning of the physical properties, by varying GelMA concentration, allowed tailoring of GelMA-DDS mesh size, where decreasing the GelMA concentration provided overall more sustained cumulative release (significant differences between 5%, 10%, and 15%) with a maximum of 75% over three months of release, identified to be released by diffusion. Additionally, enzymatic degradation, which more readily mimics the in vivo situation, followed a near zero-order rate, with a total release of the cargo at various rates (2–14 h) depending on GelMA concentration. Finally, the results demonstrated that Abraxane^® delivery from the hydrogel system led to a dose-dependent reduction of viability, metabolic activity, and live-cell density of triple-negative breast cancer cells in vitro. The GelMA-DDS provides a novel and simple approach for the sustained local administration of anti-cancer drugs for breast cancer recurrence. Full article

In this study, three-dimensional (3D) biopolymeric scaffolds made from collagen, silk fibroin and chitosan were successfully prepared by the freeze drying method. Dialdehyde starch (DAS) was used as a cross-linking agent for the materials. The properties of the materials were studied using density and porosity measurements, scanning electron microscope (SEM) imaging, swelling and moisture content measurements. Additionally, cytocompatibility of the materials in contact with MG-63 osteoblast-like cells was tested by live/dead staining and resazurin reduction assay on days 1, 3 and 7. It was found that new 3D materials made from collagen/silk fibroin/chitosan binary or ternary mixtures are hydrophilic with a high swelling ability (swelling rate in the range of 1680–1900%). Cross-linking of such biopolymeric materials with DAS increased swelling rate up to about 2100%, reduced porosity from 96–97% to 91–93%, and also decreased density and moisture content of the materials. Interestingly, presence of DAS did not influence the microstructure of the scaffolds as compared to non-cross-linked samples as shown by SEM. All the tested samples were found to be cytocompatible and supported adhesion and growth of MG-63 cells as shown by live–dead staining and metabolic activity test. Full article

To fabricate environmentally sensitive hydrogels with better biocompatibility, natural materials such as protein and polysaccharide have been widely used. Environmentally sensitive hydrogels can be used as a drug carrier for sustained drug release due to its stimulus responsive performance. The relationship between the internal structure of hydrogels and their drug delivery behaviors remains indeterminate. In this study, environmentally sensitive hydrogels fabricated by blending silk fibroin/chitosan with different mass ratios were successfully prepared using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (EDC)/N-Hydroxysuccinimide (NHS) cross-linking agent. Scanning-electron microscopy (SEM) images showed the microcosmic surface of the gel had a 3-D network-like and interconnected pore structure. The N₂ adsorption–desorption method disclosed the existence of macroporous and mesoporous structures in the internal structure of hydrogels. Data of compression tests showed its good mechanical performance. The swelling performance of hydrogels exhibited stimuli responsiveness at different pH and ion concentration. With the increase of pH and ion concentration, the swelling ratios of hydrogels (silk fibroin (SF)/ chitosan (CS) = 8/2 and 7/3) decreased. Methylene blue (MB) was loaded into the hydrogels to confirm the potential of sustained drug release and pH-responsive behavior. Therefore, due to the porous structure, stable mechanical strength, stimuli responsive swelling performance, and drug release behaviors, the SF/CS composite hydrogels have potential applications in controlled drug release. Full article

Targeted drug delivery systems are commonly used to improve the therapeutic index of anti-cancer drugs by increasing their selectivity and reducing systemic distribution and toxicity. Ligand-conjugated nanoparticles (NPs) can be effectively applied for active chemotherapeutic targeting to overexpressed receptors of tumor cells. In this study, transferrin (Tf) was successfully conjugated with poly-l-lactic-co-glycolic acid (PLGA) using ethylene diamine confirmed by NMR, for the loading of docetaxel trihydrate (DCT) into PLGA nanoparticles (NPs). The DCT-loaded Tf-conjugated PLGA NPs were produced by an emulsion-solvent evaporation technique, and a 3² full factorial design was used to optimize the nanoparticle formulations. The DCT-loaded Tf-conjugated PLGA NPs were characterized by FTIR spectroscopy, differential scanning calorimetry, powder X-ray diffraction (PXRD), TEM, particle size, and zeta potential analysis. In vitro release kinetics confirmed that release of DCT from the designed formulations followed a zero-order kinetics and a diffusion controlled non-Fickian release profile. The DCT-loaded Tf-conjugated PLGA NPs were evaluated in vitro in MCF-7 cells for bioactivity assessment. Cytotoxicity studies confirmed that the Tf-conjugated PLGA NPs were more active than the non-conjugated counterparts. Cell uptake studies re-confirmed the ligand-mediated active targeting of the formulated NPs. From the cell cycle analysis, the anti-cancer activity of DCT-loaded Tf-conjugated PLGA NPs was shown to occur by arresting the G₂/M phase. Full article

Poly(ethylene glycol) (PEG) is widely used as a gold standard in bioconjugation and nanomedicine to prolong blood circulation time and improve drug efficacy. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles is a well-established technique known as PEGylation, with PEGylated products have been using in clinics for the last few decades. However, it is increasingly recognized that treating patients with PEGylated drugs can lead to the formation of antibodies that specifically recognize and bind to PEG (i.e., anti-PEG antibodies). Anti-PEG antibodies are also found in patients who have never been treated with PEGylated drugs but have consumed products containing PEG. Consequently, treating patients who have acquired anti-PEG antibodies with PEGylated drugs results in accelerated blood clearance, low drug efficacy, hypersensitivity, and, in some cases, life-threatening side effects. In this succinct review, we collate recent literature to draw the attention of polymer chemists to the issue of PEG immunogenicity in drug delivery and bioconjugation, thereby highlighting the importance of developing alternative polymers to replace PEG. Several promising yet imperfect alternatives to PEG are also discussed. To achieve asatisfactory alternative, further joint efforts of polymer chemists and scientists in related fields are urgently needed to design, synthesize and evaluate new alternatives to PEG. Full article

As a polymer matrix containing a large amount of water, hydrogels have been widely used in many fields such as biology and medicine due to its similarity to extracellular matrix components, and its contact with blood, body fluids, and human tissue does not affect the metabolic processes of living organisms. However, due to the lack of unique physical properties of traditional polymer hydrogels, its further application in the high-end field is limited. With the progress of study, a series of hydrogels with special structures, such as double network hydrogel, composite hydrogel, Tetra-PEG gel, and topological gel, have improved the situation to a large extent. At the same time, the progress of research on the biocompatibility and biodegradability of hydrogels, which are expected to be used in biomedical fields, is also worthy of attention. This review introduces four such types of high-strength polymeric hydrogels and the mechanisms for improving their mechanical strength. Moreover, a discussion will be made around specific methods for imparting special physical properties to hydrogels and applications in the field of biomedicine such as cell culture, medical surgery, tissue engineering, and biosensing. At the end of the review, the main reasons and contradictions for the limits of the current applications are explained. An outlook on the future research in related fields and the importance of carrying out research in this area to promote medical progress are emphasized. Full article