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Natural and synthetic polymers are a versatile platform for developing biomaterials in the biomedical and environmental fields. Natural polymers are organic compounds that are found in nature. The most common natural polymers include polysaccharides, such as alginate, hyaluronic acid, and starch, proteins, e.g., collagen, silk, and fibrin, and bacterial polyesters. Natural polymers have already been applied in numerous sectors, such as carriers for drug delivery, tissue engineering, stem cell morphogenesis, wound healing, regenerative medicine, food packaging, etc. Various synthetic polymers, including poly(lactic acid), poly(acrylic acid), poly(vinyl alcohol), polyethylene glycol, etc., are biocompatible and biodegradable; therefore, they are studied and applied in controlled drug release systems, nano-carriers, tissue engineering, dispersion of bacterial biofilms, gene delivery systems, bio-ink in 3D-printing, textiles in medicine, agriculture, heavy metals removal, and food packaging. In the following review, recent advancements in polymer chemistry, which enable the imparting of specific biomedical functions of polymers, will be discussed in detail, including antiviral, anticancer, and antimicrobial activities. This work contains the authors’ experimental contributions to biomedical and environmental polymer applications. This review is a vast overview of natural and synthetic polymers used in biomedical and environmental fields, polymer synthesis, and isolation methods, critically assessessing their advantages, limitations, and prospects.

Biopolymer materials have been considered a “green” alternative to petroleum-based polymeric materials. Biopolymers cannot completely replace synthetic polymers, but their application should be extended as much as possible, exploiting the benefits of their low toxicity and biodegradability. This contribution describes a novel strategy for the synthesis of super-macroporous 2-hydroxyethylcellulose (HEC) cryogels. The method involves cryogenic treatment of an aqueous solution of HEC and citric acid (CA), freeze drying, and thermally induced crosslinking of HEC macrochains by CA in a solid state. The effect of reaction temperature (70–180 °C) and CA concentration (5–20 mass % to HEC) on the reaction efficacy and physico-mechanical properties of materials was investigated. Highly elastic cryogels were fabricated, with crosslinking carried out at ≥100 °C. The storage modulus of the newly obtained HEC cryogels was ca. 20 times higher than the modulus of pure HEC cryogels prepared by photochemical crosslinking. HEC cryogels possess an open porous structure, as confirmed by scanning electron microscopy (SEM), and uptake a relatively large amount of water. The swelling degree varied between 17 and 40, depending on the experimental conditions. The degradability of HEC cryogels was demonstrated by acid hydrolysis experiments.

Aripiprazole (ARZ) is an atypical antipsychotic drug used to treat a variety of mood and psychotic disorders, such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette’s syndrome. Although ARZ offers significant therapeutic benefits, its poor solubility in water requires the development of delivery systems aimed at improving the solubility and bioavailability of the drug. In this work, cryogels based on two natural products—agar and β-cyclodextrin (CD)—were developed and evaluated as a drug delivery system for ARZ. The cryogels were prepared by cryogenic treatment of aqueous solutions of agar and the β-CD/ARZ complex, followed by thawing. The main characteristics of the material, including gel fraction yield, swelling degree, pore volume, elastic properties, and morphology were studied in detail. The release of ARZ from composite cryogels was assessed in two media resembling the pH in stomach and intestine. The system exhibited a pH-dependent release of ARZ, with a slower rate in acidic media (pH 1.2) than in the neutral phosphate buffer (pH 6.8). Under in vitro conditions, the amount of released ARZ over 48 h reached 33%.

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury. Drug induced liver injury (DILI) is an important cause acute liver failure. Here the authors report that serum Mg2+ serum levels decrease in patients with DILI as well as in preclinical animal models treated with acetaminophen overdose, and that early intervention targeting the Mg2+ transporter Cyclin M4 may be beneficial for acetaminophen overdose in preclinical models.

Background/Objectives: In this study, we present a green, scalable platform for the production of water-dispersible powders co-encapsulating the lipophilic bioactives curcumin (Cur) and eugenol (Eug) within the amphiphilic polymer Soluplus® (SP) via low-temperature spray drying. Methods: The amount of Cur (1%, 5%, and 10%) and Eug (5%, 10%, 15%, and 20%) was varied to achieve single- and double-loaded water-soluble powders with the maximum amount of active substances. The powders containing a higher loading of Cur, 5% and 10% (and Eug), were obtained from water/ethanol mixtures (2:1 and 5:1 v/v ratio), while the formulation with 1% of Cur was spray-dried by using water as a solvent. Results: By leveraging aqueous or aqueous–ethanolic feed systems, we achieved high loading of the bioactive substances—up to 10% Cur and 20% Eug (w/w)—while minimizing organic solvent use. Myo-inositol was incorporated as a stabilizing excipient to modulate particle morphology, improve powder flowability, and enhance redispersibility. Physicochemical characterization revealed nanoscale micellization (53–127 nm), amorphization of both actives as confirmed by XRD and DSC, and the absence of crystalline residue. Encapsulation efficiencies exceeded 95% for Cur and 93% for Eug. Dissolution tests demonstrated a rapid release from the 5% Cur/5% Eug formulation (>85% in 5 min), while higher-loaded single-formulations showed progressively slower release (up to 45 min). Conclusions: This work demonstrates a robust and environmentally responsible encapsulation strategy, suitable for delivering poorly water-soluble phytochemicals with potential applications in oral nutraceuticals and pharmaceutical dosage forms.

Budesonide is a mineral corticoid applied in the local therapy of pediatric atopic dermatitis. Unfortunately, its dermal administration is hindered by the concomitant adverse effects and its physicochemical properties. The characteristic pH change in the atopic lesions can be utilized for the preparation of a pH-sensitive nanocarrier. In this view, the formulation of Eudragit L 100 nanoparticles as a budesonide delivery platform could provide more efficient release to the desired site, improve its penetration, and subsequently lower the undesired effects. In this study, budesonide-loaded Eudragit L100 nanoparticles were prepared via the nanoprecipitation method (mean diameter 57 nm, −31.2 mV, and approx. 90% encapsulation efficiency). Their safety was proven by cytotoxicity assays on the HaCaT keratinocyte cell line. Further, the drug-loaded nanoparticles were incorporated into two types of hydrogels based on methylcellulose or Pluronic F127. The formulated hydrogels were characterized with respect to their pH, occlusion, rheology, penetration, spreadability, and drug release. In conclusion, the developed hydrogels containing budesonide-loaded nanoparticles showed promising potential for the pediatric treatment of atopic dermatitis.

We report the elaboration of redox-responsive functional micellar nanocarriers designed for triggered release of caffeic acid phenethyl ester (CAPE) in cancer therapy. Three-layered micelles, comprising a poly(ε-caprolactone) (PCL) core, a middle poly(acrylic acid)/poly(ethylene oxide) (PAA/PEO) layer and a PEO outer corona, were prepared by co-assembly of PEO113-b-PCL35-b-PEO113 and PAA13-b-PCL35-b-PAA13 amphiphilic triblock copolymers in aqueous media. The preformed micelles were loaded with CAPE via hydrophobic interactions between the drug molecules and PCL core, and subsequently crosslinked by reaction of carboxyl groups from PAA and a disulfide crosslinking agent. The reaction of crosslinking took place in the middle layer of the nanocarriers without changing the encapsulation efficiency (EE~90%) of the system. The crosslinked polymeric micelles (CPMs) exhibited superior structural stability and did not release CAPE in phosphate buffer (pH 7.4). However, in weak acidic media and in the presence of 10 mM reducing agent (dithiothreitol, DTT), the payload was released at a high rate from CPMs due to the breakup of disulfide linkages. The physicochemical properties of the nanocarriers were investigated by dynamic and electrophoretic light scattering (DLS and ELS) and atomic force microscopy (AFM). The rapid release of CAPE under intracellular-like conditions and the lack of premature drug release in media resembling the blood stream (neutral pH) make the developed CPMs a promising candidate for controllable drug release in the microenvironment of tumors.

Nanogels are attractive drug delivery systems that provide high loading capacity for drug molecules, improve their stability, and increase cellular uptake. Natural antioxidants, especially polyphenols such as resveratrol, are distinguished by low aqueous solubility, which hinders therapeutic activity. Thus, in the present study, resveratrol was incorporated into nanogel particles, aiming to improve its protective effects in vitro. The nanogel was prepared from natural substances via esterification of citric acid and pentane-1,2,5-triol. High encapsulation efficiency (94.5%) was achieved by applying the solvent evaporation method. Dynamic light scattering, atomic force microscopy, and transmission electron microscopy revealed that the resveratrol-loaded nanogel particles were spherical in shape with nanoscopic dimensions (220 nm). In vitro release tests showed that a complete release of resveratrol was achieved for 24 h, whereas at the same time the non-encapsulated drug was poorly dissolved. The protective effect of the encapsulated resveratrol against oxidative stress in fibroblast and neuroblastoma cells was significantly stronger compared to the non-encapsulated drug. Similarly, the protection in a model of iron/ascorbic acid-induced lipid peroxidation on rat liver and brain microsomes was higher with the encapsulated resveratrol. In conclusion, embedding resveratrol in this newly developed nanogel improved its biopharmaceutical properties and protective effects in oxidative stress models.

Resveratrol could be applied in wound healing therapies because of its antioxidant, anti-inflammatory and antibacterial effects. However, the main limitation of resveratrol is its low aqueous solubility. In this study, resveratrol was included in hydroxypropyl-β-cyclodextrin complexes and further formulated in Pluronic F-127 hydrogels for wound treatment therapy. IR-spectroscopy and XRD analysis confirmed the successful incorporation of resveratrol into complexes. The wound-healing ability of these complexes was estimated by a scratch assay on fibroblasts, which showed a tendency for improvement of the effect of resveratrol after complexation. The antimicrobial activity of resveratrol in aqueous dispersion and in the complexes was evaluated on methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans strains. The results revealed a twofold decrease in the MIC and stronger inhibition of the metabolic activity of MRSA after treatment with resveratrol in the complexes compared to the suspended drug. Furthermore, the complexes were included in Pluronic hydrogel, which provided efficient drug release and appropriate viscoelastic properties. The formulated hydrogel showed excellent biocompatibility which was confirmed via skin irritation test on rabbits. In conclusion, Pluronic hydrogel containing resveratrol included in hydroxypropyl-β-cyclodextrin complexes is a promising topical formulation for further studies directed at wound therapy.

Caffeine is a well-known xanthine that possesses antioxidant effects that could contribute to its application in different skin disorders. In order to enhance its effects, approaches for improving its permeation and penetration through skin layers could be applied. This study emphasizes the preparation of caffeine–cyclodextrin complex and its formulation in carbopol hydrogel. The complex was developed at a 1:1 molar ratio between caffeine and hydroxypropyl-β-cyclodextrin. It was found that the complex enhanced the radical scavenging activity of caffeine against ABTS radical as well as the protective effects against H2O2-induced oxidative stress in L929 fibroblasts. Then, the complex was formulated in hydrogel by applying 1% carbopol. The spreadability and penetration of the loaded hydrogel were improved in comparison with the empty hydrogel. The results revealed that the system could be appropriate for therapies of skin disorders, and its wound healing abilities could be further investigated.