Bioactive Macromolecules Research Articles

Efficacy of chondroitin sulfate as an emerging biomaterial for cancer-targeted drug delivery: A short review.

The global increase in cancer incidence over the past decade highlights the urgent need for more effective therapeutic strategies. Conventional cancer treatments face challenges such as drug resistance and off-target toxicity, which affect healthy tissues. Chondroitin sulfate (CHDS), a naturally occurring bioactive macromolecule, has gained attention because of its biocompatibility, biodegradability, and low toxicity, positioning it as an ideal candidate for cancer-targeted drug delivery systems. This review highlights the potential of CHDS as an emerging biomaterial in cancer therapy, focusing on its unique biological properties and applications in drug delivery platforms. Furthermore, we discuss the advantages of CHDS-based biomaterials in enhancing cancer treatment efficacy and minimizing side effects, in order to provide a comprehensive reference for future research on CHDS-based cancer therapeutics.

Extraction, purification, structural characterization, bioactivities, modifications and structure–activity relationship of polysaccharides from Ophiopogon japonicus: a review

Ophiopogon japonicus (Thunb.) Ker Gawl., is a traditional Chinese medicine (TCM) with a history of thousands of years. O. japonicus polysaccharides (OJPs), as one of the main active ingredient, are a kind of representative pharmacological bioactive macromolecules and mainly composed of Glc and Fru with molecular weight between 2.48 and 325 kDa. OJPs have a variety of biological activities, such as hypoglycemic, cardioprotective, immunomodulatory, improvement of obesity, and renal protective activity. In this review, the extraction, purification and structural characterization of OJPs were systematically reviewed, and its biological function, molecular mechanism and structure–activity relationship were analyzed. Additionally, this review summarized and found that structural modifications such as liposome modification, sulfation modification, and polyethylene glycol modification have improved the pharmacological activity and bioavailability of OJPs. Overall, this work will help to better understand OJPs and provide a theoretical review of their further development and utilization in the field of medicine and health food.

Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics.

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as delivery vehicles include the induction of a protracted immune response that results in their rapid systemic clearance, manufacturing cost, lack of stability, and their biocompatibility. Extracellular vesicles (EVs) are a heterogeneous class of endogenous biologically produced lipid bilayer nanoparticles that mediate intercellular communication by carrying bioactive macromolecules capable of modifying cellular phenotypes to local and distant cells. By genetic, chemical, or metabolic methods, extracellular vesicles (EVs) can be engineered to display targeting moieties on their surface while transporting specific cargo to modulate pathological processes following uptake by target cell populations. This review will survey the types of EVs, their composition and cargoes, strategies employed to increase their targeting, uptake, and cargo release, and their potential as targeted anti-cancer therapeutic delivery vehicles.

A Review of Antimicrobial Peptides: Structure, Mechanism of Action, and Molecular Optimization Strategies

Antimicrobial peptides (AMPs) are bioactive macromolecules that exhibit antibacterial, antiviral, and immunomodulatory functions. They come from a wide range of sources and are found in all forms of life, from bacteria to plants, vertebrates, and invertebrates, and play an important role in controlling the spread of pathogens, promoting wound healing and treating tumors. Consequently, AMPs have emerged as promising alternatives to next-generation antibiotics. With advancements in systems biology and synthetic biology technologies, it has become possible to synthesize AMPs artificially. We can better understand their functional activities for further modification and development by investigating the mechanism of action underlying their antimicrobial properties. This review focuses on the structural aspects of AMPs while highlighting their significance for biological activity. Furthermore, it elucidates the membrane targeting mechanism and intracellular targets of these peptides while summarizing molecular modification approaches aimed at enhancing their antibacterial efficacy. Finally, this article outlines future challenges in the functional development of AMPs along with proposed strategies to overcome them.

In vitro digestion and fecal fermentation of Tremella fuciformis exopolysaccharides from basidiospore-derived submerged fermentation

Tremella fuciformis polysaccharides (TFPS) belong to natural bioactive macromolecule with both edible and medicinal value, possessing much bioactivities such as anti-tumor, antioxidant, antidiabetics, and immunomodulatory. Currently, the production of TFPS through submerged fermentation (TFPS-1) is gradually replacing the polysaccharides extracted from the fruiting body due to improved fermentation efficiency and reduced separation costs. However, it is still unclear about the effect of TFPS-1 on gastrointestinal digestion and gut microbial fermentation, which is directly related to the function of its biological activity. This study aimed to illustrate the effect of TFPS-1 on digestive process through in vitro digestion and fecal fermentation. TFPS-1 was indigestible during the simulated gastrointestinal tract. But TFPS-1 can be digested by intestinal flora leading to alterations in the total polysaccharides content, molecular weight, and apparent viscosity. Moreover, TFPS-1 regulated the composition of gut microbial, lowering the proportion of Firmicutes to Bacteroidetes and enhancing the abundances of Parabacteroides and Bacteroides. The change of intestinal flora produced more short chain fatty acids and lowered the pH. The KEGG metabolic pathway analysis indicated that TFPS-1 enriched lipid metabolism, glycan biosynthesis and metabolism, and biosynthesis of other secondary metabolites. This study demonstrated that T. fuciformis fermented polysaccharide can be a potential prebiotic to optimize intestinal flora homeostasis and maintain host intestinal health.

A Review of Ganoderma lucidum Polysaccharide: Preparations, Structures, Physicochemical Properties and Application.

Ganoderma lucidum (GL) is a kind of edible fungus with various functions and a precious medicinal material with a long history. Ganoderma lucidum polysaccharide (GLP) is one of the main bioactive substances in GL, with anti-tumor, anti-oxidation, anti-cancer, and other biological activities. GLP is closely related to human health, and the research on GLP is getting deeper. This paper reviewed the extraction and purification methods of GLP, the relationship between structure and activity, and the qualitative and quantitative methods. This review provides solutions for the analysis and application of GLP. At the same time, some new methods for extraction, purification and analysis of GLP, the relationship between advanced structures and activity, and future applications of and research into GLP were emphasized. As a kind of bioactive macromolecule, GLP has unique functional properties. Through the comprehensive summary of the extraction, purification, and analysis of GLP and its future prospects, we hope that this review can provide valuable reference for the further study of GLP.

Novel Synergistic Approach for Bioactive Macromolecules: Evaluating the Efficacy of Goat Placenta Extract in PEGylated Liposomes and Microspicules for Chemotherapy-Induced Hair Loss.

Chemotherapy-induced hair loss is a distressing side effect of cancer treatment, and medical interventions are often needed to address this problem. The objectives of this study were to evaluate the bioactivity of goat placenta (GP) extract on both normal and chemotherapy-induced hair cells and to develop PEGylated liposomes (PL) and microspicule (MS) formulations for promoting hair growth in patients with chemotherapy-induced hair loss. The bioactivities of GP extract on human follicle dermal papilla (HFDP) cells and cells damaged by chemotherapy were assessed. GP extract was incorporated into PLs and MS gel (PL-MS) and then investigated in vitro skin permeation and in vivo studies on the scalps of patients with chemotherapy-induced hair loss. GP extract stimulated HFDP cell proliferation in both normal and cisplatin-damaged cells. PL nanovesicles and MS gel worked synergistically to deliver macromolecular proteins into the skin and hair follicles. The application of GP extract-loaded PL-MS to the scalps of chemotherapy-treated patients for 12 weeks significantly enhanced the hair growth rate, without causing skin irritation. In conclusion, GP extract promoted the proliferation of hair cells damaged by chemotherapy, when this extract, combined with PL-MS, effectively delivered bioactive macromolecules across the skin and hair follicles, resulting in successful regrowth of hair post-chemotherapy.

Collagen-rich liver-derived extracellular matrix hydrogels augment survival and function of primary rat liver sinusoidal endothelial cells and hepatocytes

Liver sinusoidal endothelial cells (LSECs) are key targets for addressing metabolic dysfunction-associated steatotic liver disease (MASLD). However, isolating and culturing primary LSECs is challenging due to rapid dedifferentiation, resulting in loss of function. The extracellular matrix (ECM) likely plays a crucial role in maintaining the fate and function of LSECs. In this study, we explored the influence of liver-ECM (L-ECM) on liver cells and developed culture conditions that maintain the differentiated function of liver cells in vitro for prolonged periods. Porcine liver-derived L-ECM, containing 34.9 % protein, 0.045 % glycosaminoglycans, and negligible residual DNA (41.2 ng/mg), was utilized to culture primary rat liver cells in generated hydrogels. Proteomic analyses and molecular weight distribution of proteins of solubilized L-ECM revealed the typical diverse ECM core matrisome, with abundant collagens. L-ECM hydrogels showed suitable stiffness and stress relaxation properties. Furthermore, we demonstrated that collagen-rich L-ECM hydrogels enhanced LSECs' and hepatocytes' viability, and reduced the dedifferentiation rate of LSECs. In addition, hepatocyte function was maintained longer by culture on L-ECM hydrogels compared to traditional culturing. These beneficial effects are likely attributed to the bioactive macromolecules including collagens, and mechanical and microarchitectural properties of the L-ECM hydrogels.

Architecting Multicompartmentalized, Giant Vesicles with Recombinant Fusion Proteins.

We present a straightforward strategy for constructing giant, multicompartmentalized vesicles using recombinant fusion proteins. Our method leverages the self-assembly of globule-zipper-elastin-like polypeptide fusion protein complexes in aqueous conditions, eliminating the need for organic solvents and chemical conjugation. By employing the thin-film rehydration method, we have successfully encapsulated a diverse range of bioactive macromolecules and engineered organelle-like compartments─ranging from soluble proteins and coacervate droplets to vesicles─within these protein-assembled giant vesicles. This approach also facilitates the integration of water-soluble block copolymers, enhancing the structural stability and functional versatility of the vesicles. Our results suggest that these multicompartment giant protein vesicles not only mimic the complex architecture of living cells but also support biochemically distinct reactions regulated by functionally folded proteins, providing a robust model for studying cellular processes and designing microreactor systems. This work highlights the transformative potential of self-assembling recombinant fusion proteins in artificial cell design.

The landscape of clinical trials in corneal regeneration: A systematic review of tissue engineering approaches in corneal disease.

The limited availability of a healthy donor cornea and the incidence of allograft failure led researchers to seek other corneal substitutes via tissue engineering. Exploring the trend of clinical trials of the cornea with the vision of tissue engineering provides an opportunity to reveal future potential corneal substitutes. The results of this clinical trial are beneficial for future study designs to overcome the limitations of current therapeutic approaches. In this study, registered clinical trials of bio-based approaches were reviewed for corneal regeneration on March 22, 2024. Among the 3955 registered trials for the cornea, 392 trials were included in this study, which categorized in three main bio-based scaffolds, stem cells, and bioactive macromolecules. In addition to the acellular cornea and human amniotic membrane, several bio-based materials have been introduced as corneal substrates such as collagen, fibrin, and agarose. However, some synthetic materials have been introduced in recent studies to improve the desired properties of bio-based scaffolds for corneal substitutes. Nevertheless, new insights into corneal regenerative medicine have recently emerged from cell sheets with autologous and allogeneic cell sources. In addition, the future perspective of corneal regeneration is described through a literature review of recent experimental models.

Exosomal microRNAs in lung cancer: a narrative review.

Exosomes are nanoscale extracellular vesicles secreted by cells, which can release bioactive macromolecules, such as microRNA (miRNA) to receptor cells. Exosomes can efficiently penetrate various biological barriers which mediate intercellular communication. MiRNA are a class of non-coding RNA that primarily regulate messenger RNA (mRNA) at the post-transcriptional level. MiRNA is abundant in exosomes, which plays an important role by being transported and released through exosomes secreted by lung cancer cells. This review aims to elucidate the roles of exosome-derived miRNAs in lung cancer. We focused on the roles of exosome-derived miRNAs in cancer occurrence and development, including angiogenesis, cell proliferation, invasion, metastasis, immune escape, drug resistance, and their clinical value as new diagnostic and prognostic markers for lung cancer. Exosomal miRNA can not only affect angiogenesis of lung cancer, induce epithelial-mesenchymal transformation, and promote reprogramming of tumor microenvironment, but also affect immune regulation and drug resistance transmission and participate in regulating lung cancer cell proliferation. Therefore, understanding the regulatory roles of exosomal miRNAs in tumor invasion and metastasis can provide new ideas for the treatment of lung cancer. Exosomal miRNA can provide some unique ideas on how to improve the efficiency of diagnosis and treatment of lung cancer in the future. Targeting tumor-specific exosomal miRNA represents a new strategy for clinical treatment of lung cancer, which can provide potential non-invasive biomarkers in the early diagnosis of lung cancer. Investigation of the involvement of exosomal miRNAs in the occurrence and progression of tumors can yield new opportunities for the clinical diagnosis and treatment of lung cancer.

Structure and antitumor activity of a polysaccharide from Rosa roxburghii

It is well known that Rosa roxburghii, as a homology of both medicine and food, is rich in polysaccharides. To discover bioactive macromolecules for combating cancer, the polysaccharides in R. roxburghii were investigated, leading to the purification of a polysaccharide (RRTP80–1). RRTP80–1 was measured to have an average molecular weight of 8.65 × 103 g/mol. Monosaccharide composition analysis revealed that RRTP80–1 was formed from three types of monosaccharides including arabinose, glucose, and galactose. Methylation and GC–MS analysis suggested that the backbone of RRTP80–1 consisted of →5)-α-l-Araf-(1→, →6)-α-d-Glcp-(1→, →2,5)-α-l-Araf-(1→, →4,6)-β-d-Galp-(1→, and →3)-α-l-Araf-(1→, with branch chains composed of α-l-Araf-(1→. In vivo studies indicated that RRTP80–1 exhibited inhibitory activity against the growth and proliferation of neoplasms in the zebrafish tumor xenograft model by suppressing angiogenesis. Additionally, RRTP80–1 was found to upregulate reactive oxygen species (ROS) and nitric oxide (NO) production levels in zebrafish models. All these studies suggest that RRTP80–1 activates the immune system to inhibit tumors. The potential role of the newly discovered homogeneous polysaccharide RRTP80–1 in cancer treatment was preliminarily clarified in this study.

Macromolecules with predominant β-pleated sheet proteins in extracellular vesicles released from Raphanus sativus L. var. caudatus Alef microgreens induce DNA damage-mediated apoptosis in HCT116 colon cancer cells

Plant-derived bioactive macromolecules (i.e., proteins, lipids, and nucleic acids) were prepared as extracellular vesicles (EVs). Plant-derived EVs are gaining pharmaceutical research interest because of their bioactive components and delivery properties. The spherical nanosized EVs derived from Raphanus sativus L. var. caudatus Alef microgreens previously showed antiproliferative activity in HCT116 colon cancer cells from macromolecular compositions (predominantly proteins). To understand the mechanism of action, the biological activity studies, i.e., antiproliferation, cellular biochemical changes, DNA conformational changes, DNA damage, apoptotic nuclear morphological changes, apoptosis induction, and apoptotic pathways, were determined by neutral red uptake assay, synchrotron radiation-based Fourier transform infrared microspectroscopy, circular dichroism spectroscopy, comet assay, 4′,6-diamidino-2-phenylindole (DAPI) staining, flow cytometry, and caspase activity assay, respectively. EVs inhibited HCT116 cell growth in concentration- and time-dependent manners, with a half-maximal inhibitory concentration of 675.4 ± 33.8 μg/ml at 48 h and a selectivity index of 1.5 ± 0.076. HCT116 treated with EVs mainly changed the cellular biochemical compositions in the nucleic acids and carbohydrates region. The DNA damage caused no changes in DNA conformation. The apoptotic nuclear morphological changes were associated with the increased apoptotic cell population. The apoptotic cell death was induced by both extrinsic and intrinsic pathways. EVs have potential as antiproliferative bioparticles.

Dynamics of α-glucan from Agrocybe cylindracea water extract at different developmental stages and its structure characteristics

Polysaccharides are the important bioactive macromolecules in Agrocybe cylindracea, but their changes are as yet elusive during developmental process. This study investigated the dynamic changes of polysaccharides from A. cylindracea fruiting body water extract at four developmental stages and its structure characteristics. Results revealed that the polysaccharides from A. cylindracea water extract significantly increased at the pileus expansion stage and the increased fraction could be α-glucan. The further purification and identification indicated that this α-glucan was a glycogen. It had typical morphology of β particles with a molecular weight of 1375 kDa. Its backbone comprised α-D-(1 → 4)-Glcp and α-D-(1 → 4,6)-Glcp residues at a ratio of 5:1, terminated by α-D-Glcp residue. Rheological behavior suggested that it was a Newtonian fluid at the concentration of 1 %. In addition, despite both the glycogen and natural starch were composed of D-glucose, they exhibited the entirely distinct Maltese cross characteristic and unique crystalline structure. This study is the first to demonstrate the presence of abundant glycogen in the pileus expansion stage of A. cylindracea, which provides new insights on the change patterns of fungal polysaccharides.

Chemical composition and antimicrobial study of Crossobamon orientalis body oil

Geckos and their products have been used in Asian traditional medicine. Medicinal properties of desert-dwelling Gecko species, Crossobamon orientalis remain unexplored. In this study, natural bioactive macromolecules present in oil extracted from C. orientalis (COO) and their biological activities were evaluated. Chemical constitution of COO was explored by using gas chromatography mass spectrometry. Antioxidant, antiviral, and antibacterial activities of COO extracts were assessed using various assays, including DPPH free-radical-protocol, HET-CAM method, in ovo-antiviral technique, and disc-diffusion method. GC-MS study reported 40 different compounds in COO. n-hexane and methanol extracts of COO demonstrated highest DPPH radical inhibition, with values of 70 and 63.3%, respectively. Extracts of COO in solvents, namely 1-butanol, methanol, diethyl ether, and n-hexane significantly inhibited the proliferation of four pathogenic viruses. Maximum zone of inhibition was observed for Escherichia coli (13.65 ± 0.57 mm). These findings suggest that COO possesses potent antioxidant and antimicrobial properties against viral and bacterial strains, thanks to its biologically active components having no side effects. Further studies are essential to isolate and identify individual bioactive compounds present in COO and to investigate their potential as therapeutic agents.

Melanoidin-like carbohydrate-containing macromolecules from Shanxi aged vinegar exert immunoenhancing effects on macrophage RAW264.7 cells

Bioactive macromolecule mining is important for the functional chemome analysis of traditional Chinese vinegar. In this study, we isolated and characterized carbohydrate-containing macromolecules from Shanxi aged vinegar (CCMSAV) and evaluated their immunomodulatory activity. The isolation process involved ethanol precipitation, deproteinization, decolorization, and DEAE-650 M column chromatography, resulting in the acquisition of four sub-fractions. All sub-fractions exhibited a molecular weight range of 6.92 to 16.71 kDa and were composed of 10 types of monosaccharides. Comparative analysis of these sub-fractions with two melanoidins exhibited similarities in elemental composition, spectral signature, and pyrolytic characteristics. Immunological assays confirmed the significantly enhanced cell viability, phagocytic activity, and secretion of nitric oxide, tumor necrosis factor (TNF)-α and interleukin (IL)-6 in RAW264.7 cells by all four sub-fractions. Further investigation of the immunomodulatory mechanism revealed that SAV-RP70-X, the most potent purified sub-fraction, enhanced aerobic glycolysis in macrophages and activated Toll-like receptor 2 (TLR2), TLR4, mannose receptor (MR), scavenger receptor (SR), and the dendritic cell-associated C-type lectin-1 receptor (Dectin-1). Furthermore, the activation of macrophages was associated with the MyD88/PI3K/Akt/NF-κB signaling pathway. Methylation analysis revealed that 1,4-Xylp was the most abundant glycosidic linkage in SAV-RP70-X.

A differential-targeting core-shell microneedle patch with coordinated and prolonged release of mangiferin and MSC-derived exosomes for scarless skin regeneration.

Microneedles for skin regeneration are conventionally restricted by uncontrollable multi-drug release, limited types of drugs, and poor wound adhesion. Here, a novel core-shell microneedle patch is developed for scarless skin repair, where the shell is composed of hydrophilic gelatin methacryloyl (GelMA) loaded with mangiferin, an anti-inflammatory small molecule, and the core is composed of hydrophobic poly (lactide-co-propylene glycol-co-lactide) dimethacrylates (PGLADMA) loaded with bioactive macromolecule and human mesenchymal stromal cell (hMSC)-derived exosomes. This material choice provides several benefits: the GelMA shell provides a swelling interface for tissue interlocking and rapid release of mangiferin at an early wound healing stage for anti-inflammation, whereas the PGLADMA core offers long-term encapsulation and release of exosomes (30% release in 3 weeks), promoting sustained angiogenesis and anti-inflammation. Our results demonstrate that the core-shell microneedle possesses anti-inflammatory properties and can induce angiogenesis both in vitro in terms of macrophage polarization and tube formation of human umbilical vein endothelial cells (HUVECs), and in vivo in terms of anti-inflammation, re-epithelization, and vessel formation. Importantly, we also observe reduced scar formation in vivo. Altogether, the degradation dynamics of our hydrophilic/hydrophobic materials enable the design of a core-shell microneedle for differential and prolonged release, promoting scarless skin regeneration, with potential for other therapies of long-term exosome release.

Phytofabrication of silver nanoparticles using callus extracts of natural tetraploid Trifolium pratense L. and its bioactivities

One of the main subjects of plant biotechnology is plant tissue culture and in recent years is considered a possible approach model for green and eco-friendly biosynthesis of nanoparticles. This study aimed to present calli produced from the natural tetraploid Trifolium pratense L. containing high amounts of phenolic compounds and glycosidic bioactive macromolecules and the biosynthesis of silver nanoparticles from calli. Combinatorial optimization of silver nanoparticles was achieved for the first time in this study, thanks to the stabilizing and reducing properties of hypocotyl, apical meristem, and epicotyl derived callus extracts of the natural tetraploid T. pratense L. biosynthesized nanoparticles from three different callus extracts. Callus extracts were used to create different experiments with AgNO3 at various concentrations (0.16, 0.5, 0.84, 1.18, 1.52 and 1.96 mg L-1), different temperatures (40, 50, 60, 70, 80, 90, 100°C), and different pH levels (5, 7, 10) to carry out the biosynthesis of AgNPs. Biologically synthesized AgNPs were easily monitored by color change in ultraviolet and UV-Vis spectroscopy proved to be a fast and simple method. Also, TEM, XRD, and FTIR analyses were done to characterize and confirm the formation of crystalline nanoparticles. It was determined that antibacterial activity inhibition was achieved by using the Agar-well diffusion method for antibacterial activity measurements on Gram-positive Staphylococcus aureus ATCC 25923 and Gram-negative Escherichia coli CECT 4972 bacteria. Biosynthesized AgNPs were observed in the wavelength range of 400-500 nm in the UV-VIS spectrum. TEM analysis demonstrated the size and shape of biosynthesized silver nanoparticles under different conditions. It was observed that the smaller silver nanoparticles were spherical and the larger silver nanoparticles were triangular, elliptical, and spherical shape. The XRD analysis proved the presence of Ag0 in nanoparticles and showed crystal structure for silver nanoparticles. By FTIR analysis, O-H hydroxyl groups of functional groups on the AgNP surface, H-linked OH stretching, C-H stretching, -CH stretching of -CH2 and -CH3 functional groups, C-N and carboxylate, aliphatic phosphate and primary amine stretching were expressed. Biosynthesized silver nanoparticles showed antibacterial activity against Gram-positive S. aureus ATCC 25923 bacteria, AgNP hypocotyl (1.7mm), AgNP-epicotyl (1.1mm) against Gram-negative E. coli CECT 4972 bacteria. Among the hypocotyl, apical meristem, and epicotyl callus cultures, the highest antioxidant activity was observed in the AgNPs obtained from hypocotyl-concentration experiments, with a DPPH radical activity of 52% and an ABTS radical activity of 68%. In conclusion, these findings underscore the potential of biotechnological strategies in green nanotechnology, which can be offered for developing metal nanoparticles with potential biomedicine and biotechnology applications.

Modification, Structural Characterizations, and Biological Activities of Sulfated Polysaccharides: A Review

AbstractPolysaccharides are another important class of bioactive macromolecules in organisms, in addition to proteins and nucleic acids. Numerous studies have confirmed that polysaccharides have various biological activities, including anti‐inflammatory, antiviral, antioxidant, immunomodulatory, anticancer, and other activities, which have attracted the attention of researchers in the biomedical field. In the past decade, increasing researches have found that sulfation modification can improve many physicochemical properties of polysaccharides, significantly enhance their original biological activities, and even generate new activity. Hence, sulfated polysaccharides have attracted more and more attention. A systematic review of the latest research progress and future development prospects of sulfated polysaccharides is very essential to better understand them. Hence, the study has systematically summarized current knowledge about synthesis, structural characteristics, biological activities, and potential molecular mechanisms of sulfated polysaccharides. This review provides some valuable insights and important guidance for the further study of sulfated polysaccharides.

Immobilization of Papain in Chitosan Membranes as a Potential Alternative for Skin Wounds.

Papain (an enzyme from the latex of Carica papaya) is an interesting natural bioactive macromolecule used as therapeutic alternative for wound healing due to debridement action in devitalized or necrotic tissues. However, its use in high doses can induce potential skin irritation and side effects. In this study, experiments explored the ability of chitosan membrane to immobilize papain, consequently improving enzymatic activity and controlling enzyme release. Papain-loading capacity was tested via experiments of force microscopy (AFM), scanning electron microscopy (SEM-FEG), and X-ray diffraction analyses. Fourier transform infrared spectroscopy and thermal analyses assessed the enzyme interactions with the copolymer. The investigation of the feasibility of membranes included pH on the surface, elasticity, and breaking strength measurements. The surface wettability and swelling capacity of different formulations revealed the best formulation for in vitro papain release experiments. The membranes had a transparent, rough, crystalline characteristic, which was homogeneous with the membrane within the neutrality. The immobilization of papain in the chitosan membrane resulted in a decrease in the vibration band characteristic of pure papain, suggesting a displacement in the vibration bands in the FTIR spectrum. The presence of papain decreased hydrophobicity on the surface of the membrane and disturbed the membrane's ability to swell. Chitosan membranes containing papain 2.5% (0.04 g) and 5.0% (0.08 g) preserved feasible properties and improved the enzymatic activity compared (0.87 ± 0.12 AU/mg and 1.59 ± 0.10 AU/mg) with a free papain sample (0.0042 ± 0.001 AU/mg). Concentrations of over 10% (0.16 g) led to phase separation into membranes. Chitosan membranes exhibited a slow papain release behavior adjusted via the Higushi model. The experimental achievements suggest a novel and promising method for the enhancement of papain. The results indicate the potential for prolonged bioactivity for use on wounds.