Collins N. Elangwe

Transthyretin cardiac amyloidosis (ATTR-CM), along with its light-chain counterpart, is an increasingly recognized restrictive cardiomyopathy with poor prognosis without early intervention. The pathogenic cascade begins with TTR tetramer dissociation into misfolded monomers that polymerize into amyloid fibrils infiltrating the myocardium. Approved synthetic stabilizers such as tafamidis and diflunisal have been reported to slow progression by raising the tetramer dissociation barrier, but cannot reverse existing deposits and remain inaccessible in many settings due to cost and parenteral administration. Natural polyphenols offer mechanistically diverse, orally available candidates. This review categorizes them by site of action. Class I (tetramer stabilizers) occupies the thyroxine-binding pocket, reducing aggregation-competent monomers. Class II (fibril disruptors) redirects preformed oligomers toward nontoxic species and facilitate aggregate clearance. We critically evaluate evidence from transgenic and early translational studies, emphasizing distinct therapeutic logic: stabilizers suit presymptomatic or early disease; disruptors align with established deposition. A rationally designed combination may address both initiation and propagation phases, potentially outperforming monotherapy. Translation remains constrained by poor pharmacokinetics—plasma concentrations of parent compounds typically fall orders of magnitude below in vitro effective concentrations. Bioavailability-enhancing formulations (nanoparticle encapsulation, phytosome complexes, biopolymeric hydrogels) represent the pressing research priority. While natural compounds cannot currently replace tafamidis or diflunisal, they may serve as adjunctive or preventive agents, especially in resource-limited settings where access to established therapies is restricted.

Cardiac amyloidosis is a disorder characterized by the misfolding and aggregation of proteins such as transthyretin (TTR), presenting significant therapeutic challenges. Effective treatment requires the controlled and sustained delivery of biologically active molecules to affected tissues. Flavonoids such as quercetin, curcumin, and mangiferin have shown the ability to stabilize TTR tetramers, thereby inhibiting amyloid fibril formation. Despite their promising therapeutic potential and favorable preclinical results, the clinical translation of flavonoids has been limited by poor bioavailability, rapid metabolism, and chemical instability. To ovwrcome these limitations, tunable hydrogel delivery systems have emerged as viable approach to enhance flavonoid bioavailibilty. Consequently, a controlled-release chitosan-based hydrogel drug delivery system was developed. The surface morphology of the synthesized hydrogels was examined using scanning electron microscopy, while their structural integrity and pH-responsive properties were evaluated through gel fraction and pH-dependent swelling studies respectively.

Precise control of cross‐linking parameters such as reaction time and temperature is crucial in hydrogel synthesis. This control directly governs how the polymer network forms, providing a cost‐effective way to optimize the entire process. In this paper, we examine the influence of heat treatment time on chitosan (CS)/oxidized pullulan (APUL) hydrogel to obtain biomaterials with tunable cross‐linked density, viscoelastic, and physical properties for specific applications. In order to determine the structure of the hydrogels, analyses based on scanning electron microscopy (SEM) and Fourier‐transform infrared spectroscopy (FTIR) were performed. Furthermore, the results of heat treatment time were assessed by gel fraction, swelling ratio, thermal analysis, and rheological testing. The results show that the gel fraction and elastic strength of the CS/APUL hydrogels increased from 61.7% ± 4.4% to 70.0% ± 2.8% and 795.7 ± 111.9 to 1836.0 ± 82.3 Pa respectively, as the heat treatment time increased due to increase in cross‐linking density within the hydrogel matrix. In addition, the swelling ratio of the hydrogels decreased as the incubation time increased from 0.5 to 4 h, due to the higher cross‐linking density of the network structure, which restricted water uptake. The variation of heat treatment time is a crucial parameter to obtain chitosan/oxidized pullulan hydrogels with interesting and tunable properties.

Recent advances in therapeutic strategies have emerged to address transthyretin-related amyloidosis, a progressive disorder characterized by diverse clinical manifestations including cardiomyopathy and polyneuropathy. Cardiac amyloidosis (CA), resulting from myocardial amyloid fibril deposition, induces restrictive cardiomyopathy and severe diastolic dysfunction. Among current treatment modalities, transthyretin (TTR) stabilizers have become therapeutic cornerstones, exemplified by the clinical implementation of tafamidis and ongoing trials with acoramidis. Nevertheless, persistent challenges in disease management necessitate the development of improved therapeutics. Notably, natural compounds have gained prominence as promising candidates for developing safer, less toxic TTR stabilizers that may overcome limitations of existing synthetic drugs. This review critically evaluates the most promising recently reported TTR stabilizers, with particular emphasis on natural products and their derivatives as innovative alternatives to conventional synthetic stabilizers.

This study examines the physicomechanical and special properties of polymer films composed of hyaluronic acid (HA) and zinc oxide (ZnO) nanoparticles that can be used as transdermal patches. Transdermal patches are a popular method of medical and cosmetic procedures in various disciplines, not limited to cosmetology, gynecology, oncology, etc. They have advantages such as convenience and simplicity, the possibility of uniform drug delivery, and a wide range of possible applications. These advantages make transdermal patches an important tool for various areas of medicine. However, most biopolymers used as a polymer matrix do not meet the required physicomechanical properties when creating polymer films for medical purposes. That is why hyaluronic acid with ZnO nanoparticles as a filler was chosen as a polymer base. The work examines the effect of nanoparticle concentration on the physicomechanical and special properties of hyaluronic acid-based polymer films. It has been shown that using 5 wt.% ZnO nanoparticles results in the production of a polymer film based on hyaluronic acid, with optimal mechanical parameters for the balance between the relative elongation and strength of the resulting materials and compliance with the skin texture, which is of critical importance for increasing the long-term effectiveness of the use of the obtained polymer films as a base for creating transdermal patches

Wound healing is a complex process of overlapping phases with the primary aim of the creation of new tissues and restoring their anatomical functions. Wound dressings are fabricated to protect the wound and accelerate the healing process. Biomaterials used to design dressing of wounds could be natural or synthetic as well as the combination of both materials. Polysaccharide polymers have been used to fabricate wound dressings. The applications of biopolymers, such as chitin, gelatin, pullulan, and chitosan, have greatly expanded in the biomedical field due to their non-toxic, antibacterial, biocompatible, hemostatic, and nonimmunogenic properties. Most of these polymers have been used in the form of foams, films, sponges, and fibers in drug carrier devices, skin tissue scaffolds, and wound dressings. Currently, special focus has been directed towards the fabrication of wound dressings based on synthesized hydrogels using natural polymers. The high-water retention capacity of hydrogels makes them potent candidates for wound dressings as they provide a moist environment in the wound and remove excess wound fluid, thereby accelerating wound healing. The incorporation of pullulan with different, naturally occurring polymers, such as chitosan, in wound dressings is currently attracting much attention due to the antimicrobial, antioxidant and nonimmunogenic properties. Despite the valuable properties of pullulan, it also has some limitations, such as poor mechanical properties and high cost. However, these properties are improved by blending it with different polymers. Additionally, more investigations are required to obtain pullulan derivatives with suitable properties in high quality wound dressings and tissue engineering applications. This review summarizes the properties and wound dressing applications of naturally occurring pullulan, then examines it in combination with other biocompatible polymers, such chitosan and gelatin, and discusses the facile approaches for oxidative modification of pullulan.