Search Results (26)

Resveratrol (RES), a naturally occurring polyphenolic compound with well-documented anticancer potential, is limited in clinical application due to its poor aqueous solubility and low bioavailability. This study aimed to develop RES-loaded liposomes coated sequentially with chitosan (CS) and hyaluronic acid-chitosan (HA) (RES-HA-CS-Lip) to enhance RES stability, delivery, and anticancer efficacy in breast cancer cells. HA-CS-coated liposomes were prepared using a thin-film hydration technique. Their physicochemical characteristics were thoroughly investigated through dynamic light scattering, transmission electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The optimized RES-HA-CS-Lip exhibited spherical morphology with an average particle size of 212 nm, a narrow polydispersity index (<0.4), a zeta potential of +9.04 ± 1.0 mV, and high entrapment efficiency of 82.16%. Stability studies demonstrated superior retention of size, surface charge, and encapsulation efficiency over 28 days at both 4 °C and 25 °C. In vitro release profiles at physiological and acidic pH revealed sustained drug release, with enhanced release under acidic conditions mimicking the tumor microenvironment. Antioxidant activity, assessed via DPPH and ABTS radical-scavenging assays, indicated that RES retained its radical-scavenging potential upon encapsulation. Cytotoxicity assays demonstrated markedly improved anticancer activity against MCF-7 breast cancer cells, with an IC₅₀ of 13.08 μg/mL at 48 h, while maintaining high biocompatibility toward normal HaCaT keratinocytes. RES-HA-CS-Lip demonstrated excellent stability against degradation and aggregation. Overall, these findings highlight HA-CS-coated liposomes as a promising polysaccharide-based nanocarrier that enhances stability, bioactivity, and therapeutic efficacy of RES, representing a potential strategy for targeted breast cancer therapy. Full article

Ozone (O₃) has re-emerged in periodontology for its antimicrobial, oxygenating, and immunomodulatory actions, yet its role in regeneration remains contentious. This narrative review synthesizes current evidence on adjunctive ozone use in periodontal therapy, delineates cellular constraints—especially in periodontal ligament fibroblasts (PDLFs)—and explores mitigation strategies using bioactive compounds and advanced delivery platforms. Two recent meta-analyses indicate that adjunctive ozone with scaling and root planing yields statistically significant reductions in probing depth and gingival inflammation, with no significant effects on bleeding on probing, plaque control, or clinical attachment level; interpretation is limited by heterogeneity of formulations, concentrations, and delivery methods. Mechanistically, ozone imposes a dose-dependent oxidative burden that depletes glutathione and inhibits glutathione peroxidase and superoxide dismutase, precipitating lipid peroxidation, mitochondrial dysfunction, ATP depletion, and PDLF apoptosis. Concurrent activation of NF-κB and upregulation of IL-6/TNF-α, together with matrix metalloproteinase-mediated extracellular matrix degradation and tissue dehydration (notably with gaseous applications), further impairs fibroblast migration, adhesion, and ECM remodeling, constraining regenerative potential. Emerging countermeasures include co-administration of polyphenols (epigallocatechin-3-gallate, resveratrol, curcumin, quercetin), coenzyme Q10, vitamin C, and hyaluronic acid to restore redox balance, stabilize mitochondria, down-modulate inflammatory cascades, and preserve ECM integrity. Nanocarrier-based platforms (nanoemulsions, polymeric nanoparticles, liposomes, hydrogels, bioadhesive films) offer controlled ozone release and co-delivery of protectants, potentially widening the therapeutic window while minimizing cytotoxicity. Overall, current evidence supports ozone as an experimental adjunct rather than a routine regenerative modality. Priority research needs include protocol standardization, dose–response definition, long-term safety, and rigorously powered randomized trials evaluating bioactive-ozone combinations and nanocarrier systems in clinically relevant periodontal endpoints. Full article

Antrodia camphorata (AC), a medicinal fungus native to Taiwan, contains bioactive compounds such as triterpenoids with anticancer properties. However, their high lipophilicity results in poor aqueous solubility and limited bioavailability, restricting their therapeutic application. To address this issue, a nanoparticle-based delivery system was developed using chitosan, alginate, and hyaluronic acid to encapsulate AC extracts. AC-loaded nanoparticles (AC-NPs) with a particle size less than 100 nm improved drug solubility and facilitated intracellular accumulation. Assessment of cytotoxicity revealed that AC-NPs significantly and more effectively suppressed the growth of breast cancer cells than free AC extracts. After 72 h, IC₅₀ values for MDA-MB-231 (triple-negative) and MCF-7 (estrogen receptor-positive) were 46.9 and 75.6 μg/mL, respectively, with greater sensitivity observed in MDA-MB-231 cells. AC-NPs exhibited minimal toxicity toward normal mammary epithelial cells (NMuMG), indicating good biocompatibility. Fluorescently labeled AC-NPs showed rapid, time-dependent uptake in both cancer cell lines. Particularly, MDA-MB-231 cells exhibited rapid internalization, whereas MCF-7 cells likely benefited from hyaluronic acid-mediated targeting of CD44 receptors. In conclusion, AC-NPs enhanced the solubility, cellular uptake, and anticancer efficacy of AC while maintaining biocompatibility, thereby suggesting their robust potential as nanocarrier platforms for breast cancer therapy. Full article

Global concerns about environmental pollution, poor waste management, and the rise in antimicrobial resistance due to uncontrolled antibiotic use have driven researchers to seek alternative, multifaceted solutions. Plants, animals, microorganisms, and their processing wastes serve as valuable sources of natural biopolymers and bioactive compounds. Through nanotechnology, these can be assembled into formulations with enhanced antimicrobial properties, high safety, and low toxicity. This review explores polysaccharides, including chitosan, alginate, starch, pectin, cellulose, hemicellulose, gums, carrageenan, dextran, pullulan, and hyaluronic acid, used in nanotechnology, highlighting their advantages and limitations as nanocarriers. Addressing the global urgency for alternative antimicrobials, we examined natural compounds derived from plants, microorganisms, and animals, such as phytochemicals, bacteriocins, animal antimicrobial peptides, and proteins. Focusing on their protection and retained activity, this review discusses polysaccharide-based nanoformulations with natural antimicrobials, including nanoparticles, nanoemulsions, nanocapsules, nanoplexes, and nanogels. Special emphasis is placed on strategies and formulations for the encapsulation, entrapment, and conjugation of natural compounds using polysaccharides as protective carriers and delivery systems, including a brief discussion on their future applications, prospects, and challenges in scaling up. Full article

Autoimmune diseases are driven by chronic inflammation and oxidative stress, thus requiring innovative therapeutic approaches. Polymeric nanotherapeutics incorporating antioxidant bioactive compounds offer a promising strategy for immune modulation and enhanced drug delivery. This review explores the application of polymer-based nanocarriers for improving the solubility, bioavailability, and targeted delivery of antioxidant compounds in autoimmune disease treatment. A comprehensive analysis of recent advancements in polymeric nanoformulations, including poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), chitosan, and hyaluronic acid, was conducted. The therapeutic efficacy of various antioxidant-loaded nanoparticles has been assessed in both preclinical and clinical studies. Phenolic antioxidants, such as resveratrol, curcumin, quercetin, and epigallocatechin-3-gallate, exhibit potent anti-inflammatory effects; however, their poor solubility limits their clinical application. Nanocarriers such as dendrosomes, tannic acid-based reactive oxygen species (ROS)-scavenging nanoparticles, and folic acid-functionalized systems enhance drug stability, controlled drug release, and macrophage targeting. Carotenoid and bilirubin nanoparticles further demonstrate immunomodulatory effects in multiple sclerosis, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Polymeric antioxidant nanotherapeutics provide targeted and sustained drug delivery, offering improved efficacy and reduced toxicity. Future research should focus on optimizing these nanocarriers for clinical translation and patient-centered therapeutic strategies. Full article

Thyroid cancer (TC) is a significant global health issue that exhibits notable heterogeneity in incidence and outcomes. In low-resource settings such as Africa, delayed diagnosis and limited healthcare access exacerbate mortality rates. Among follicular cell-derived thyroid cancers—including papillary (PTC), follicular (FTC), anaplastic (ATC), and poorly differentiated (PDTC) subtypes—the role of CD44 variants has emerged as a critical factor influencing tumor progression and multidrug resistance (MDR). CD44, a transmembrane glycoprotein, and its splice variants (CD44v) mediate cell adhesion, migration, and survival, contributing to cancer stem cell (CSC) maintenance and therapy resistance. Differential expression patterns of CD44 isoforms across TC subtypes have shown diagnostic, prognostic, and therapeutic implications. Specifically, CD44v6 expression in PTC has been correlated with metastasis and aggressive tumor behavior, while in FTC, its expression aids in distinguishing malignant from benign lesions. Furthermore, CD44 contributes to MDR through enhanced drug efflux via ABC transporters, apoptosis evasion, and CSC maintenance via the Wnt/β-catenin and PI3K/Akt pathways. Targeted therapies against CD44 such as monoclonal antibodies, hyaluronic acid-based nanocarriers, and gene-editing technologies hold promise in overcoming MDR. However, despite the mounting evidence supporting CD44-targeted strategies in various cancers, research on this therapeutic potential in TC remains limited. This review synthesizes existing knowledge on CD44 variant expression in follicular cell-derived thyroid cancers and highlights potential therapeutic strategies to mitigate MDR, particularly in high-burden regions, thereby improving patient outcomes and survival. Full article

Background/Objectives: The study aims to investigate an improved version of lipid nanocarriers (NLCs) (formulated with functional coconut butter and marula oil) by designing hyaluronic acid (HA) decorated NLC co-loaded with dual UVA (butyl methoxy dibenzoyl methane, BMDBM), UVB absorbers (ethyl-hexyl-salicylate, EHS) and a Raspberry rich polyphenols fraction (RPRF) for development of more natural NLC-based to-pical formulations. Methods: Quality and quantitative attributes of classic- and HA-NLC have been assigned based on particle size, electrokinetic potential, encapsulation efficiency, spectroscopic characteristics, and high-resolution mass spectrometry. To establish the performance profile of antioxidant activity, release of active substances, sun blocking action, and photostability, in vitro studies were conducted. Results: NLC with an average size of ~150 nm and zeta potentials < −39.5 mV showed 80% and 93.1% of encapsulation efficiency for BMDBM and EHS, and up to 83% for natural RPRF. A long-lasting release of absorbers, with a maximum cumulative release of 2.1% BMDBM and 4.6% EHS was detected. NLC-UV Abs-RPRF-HA assured 72.83% radical scavenging activity. The IC₅₀ for HA-NLC-UV Abs-RPRF was 6.25-fold lower than NLC-UV Abs-HA, which reflects the greater free radical scavenging action. The conditioned NLC–UV Abs-RPRF-HA cream was able to provide a sun protection factor value of 52 and UVA-PF value of 81, which underlines an impressive removal of both categories of UVA and UVB radiation. A significant photoprotective upregulation, four-fold for the topical formulation with NLC-UV Abs-RPRF-HA, resulted after a simulated irradiation process. Conclusions: HA decorated-NLC-conditioned creams might provide a useful platform for developing na-tural and sophisticated dermal delivery systems, for influencing skin permeability, and for synergistically imparting antioxidant and photoprotective actions to cosmetic pro-ducts. Full article

New strategies for enhancing drug delivery to the blood–brain barrier (BBB) represent a major challenge in treating cerebral diseases. Nanoemulsion-based nanocarriers represent an ideal candidate to improve drug delivery thanks to their versatility in functionalization and cargo protection. In this work, a paclitaxel-loaded nano-emulsion has been firstly functionalized and stabilized with two layers constituted of chitosan and hyaluronic acid, and, secondly, the latter has been conjugated to the CRT peptide. CRT is a bioactive peptide that selectively recognizes bEnd.3 cells, a model of the BBB, thanks to its interactions with transferrin (Tf) and its receptor (TfR). Cytotoxic results showed a 41.5% higher uptake of CRT functionalized nano-emulsion than the negative control, demonstrating the ability of this novel tool to be accumulated in brain endothelium tissue. Based upon these results, our approach can be fully generalizable to the design of multifunctional nanocarriers for delivery of therapeutic agents to the central nervous systems. Full article

Potent synthetic drugs, as well as biomolecules extracted from plants, have been investigated for their selectivity toward cancer cells. The main limitation in cancer treatment is the ability to bring such molecules within each single cancer cell, which requires accumulation in the peritumoral region followed by homogeneous spreading within the entire tissue. In the last decades, nanotechnology has emerged as a powerful tool due to its ability to protect the drug during blood circulation and allow enhanced accumulation around the leaky regions of the tumor vasculature. However, the ideal size for accumulation of around 100 nm is too large for effective penetration into the dense collagen matrix. Therefore, we propose a multistage system based on graphene oxide nanosheet-based quantum dots (GOQDs) with dimensions that are 12 nm, functionalized with hyaluronic acid (GOQDs-HA), and deposited using the layer-by-layer technique onto an oil-in-water nanoemulsion (O/W NE) template that is around 100 nm in size, previously stabilized by a biodegradable polymer, chitosan. The choice of a biodegradable core for the nanocarrier is to degrade once inside the tumor, thus promoting the release of smaller compounds, GOQDs-HA, carrying the adsorbed anticancer compound, which in this work is represented by curcumin as a model bioactive anticancer molecule. Additionally, modification with HA aims to promote active targeting of stromal and cancer cells. Cell uptake experiments and preliminary penetration experiments in three-dimensional microtissues were performed to assess the proposed multistage nanocarrier. Full article

Polysaccharides are gaining increasing attention for their relevance in the production of sustainable materials. In the domain of biomaterials, polysaccharides play an important role as hydrophilic components in the design of amphiphilic block copolymers for the development of drug delivery systems, in particular nanocarriers due to their outstanding biocompatibility, biodegradability, and structural versatility. The presence of a reducing end in polysaccharide chains allows for the synthesis of polysaccharide-based block copolymers. Compared with polysaccharide-based graft copolymers, the structure of block copolymers can be more precisely controlled. In this review, the synthesis methods of polysaccharide-based amphiphilic block copolymers are discussed in detail, taking into consideration the structural characteristics of polysaccharides. Various synthetic approaches, including reductive amination, oxime ligation, and other chain-end modification reactions, are explored. This review also focuses on the advantages of polysaccharides as hydrophilic blocks in polymeric nanocarriers. The structure and unique properties of different polysaccharides such as cellulose, hyaluronic acid, chitosan, alginate, and dextran are described along with examples of their applications as hydrophilic segments in the synthesis of amphiphilic copolymers to construct nanocarriers for sustained drug delivery. Full article

Improving the biopharmaceutical properties of glucocorticoids (increasing local bioavailability and reducing systemic toxicity) is an important challenge. The aim of this study was to develop a dexamethasone phosphate (DexP) delivery system based on hyaluronic acid (HA) and a water-soluble cationic chitosan derivative, diethylaminoethyl chitosan (DEAECS). The DexP delivery system was a polyelectrolyte complex (PEC) resulting from interpolymer interactions between the HA polyanion and the DEAECS polycation with simultaneous incorporation of zinc ions as a cross-linking agent into the complex. The developed PECs had a hydrodynamic diameter of 244 nm and a ζ-potential of +24.4 mV; the encapsulation efficiency and DexP content were 75.6% and 45.4 μg/mg, respectively. The designed DexP delivery systems were characterized by both excellent mucoadhesion and prolonged drug release (approximately 70% of DexP was released within 10 h). In vitro experiments showed that encapsulation of DexP in polysaccharide nanocarriers did not reduce its anti-inflammatory activity compared to free DexP. Full article

In this review, a compilation of articles in databases on the extraction methods and applications of hyaluronic acid (HA) was carried out. HA is a highly hydrated component of different tissues, including connective, epithelial, and neural. It is an anionic, linear glycosaminoglycan (GAG) primarily found in the native extracellular matrix (ECM) of soft connective tissues. Included in the review were studies on the extraction methods (chemical, enzymatical, combined) of HA, describing advantages and disadvantages as well as news methods of extraction. The applications of HA in food are addressed, including oral supplementation, biomaterials, medical research, and pharmaceutical and cosmetic industry applications. Subsequently, we included a section related to the structure and penetration routes of the skin, with emphasis on the benefits of systems for transdermal drug delivery nanocarriers as promoters of percutaneous absorption. Finally, the future trends on the applications of HA were included. This final section contains the effects before, during, and after the application of HA-based products. Full article

Nanogels are a prominent research topic in biomedical and drug delivery applications. The versatility of their chemistry allows them to be tailored both to carry and release a wide range of active molecules, and to target specific tissues or cell types. Within a vast field of possible chemical designs, nanogels based on hyaluronic acid seem particularly interesting from the standpoint of dermatological and cosmetic applications, due to the well-known involvement of hyaluronic acid in several fundamental processes related to skin health and ageing. In spite of this, relatively few studies about these nanocarriers and their potential skin-related benefits have appeared so far in the literature. With the aim to stimulate further interest in the topic, in this review, we provide information on hyaluronic acid-based nanogels, including their key physicochemical properties, their typical drug release behavior, and the main synthetic methodologies. The latter include: approaches based on spontaneous self-assembly of polymer molecules; approaches based on chemical cross-linking, where nanogel formation is promoted by covalent bonds between polymer chains; and hybrid approaches that leverage a combination of the above two mechanisms. We believe this body of information, which we collected by going through the relevant literature from the past 10–15 years, offers cosmetic formulators plenty of options to design innovative products. Full article

As a Food and Drug Administration (FDA)-approved molecular-targeted chemotherapeutic drug, sorafenib (SF) can inhibit angiogenesis and tumor cell proliferation, leading to improved patient overall survival of hepatocellular carcinoma (HCC). In addition, SF is an oral multikinase inhibitor as a single-agent therapy in renal cell carcinoma. However, the poor aqueous solubility, low bioavailability, unfavorable pharmacokinetic properties and undesirable side effects (anorexia, gastrointestinal bleeding, and severe skin toxicity, etc.) seriously limit its clinical application. To overcome these drawbacks, the entrapment of SF into nanocarriers by nanoformulations is an effective strategy, which delivers SF in a target tumor with decreased adverse effects and improved treatment efficacy. In this review, significant advances and design strategies of SF nanodelivery systems from 2012 to 2023 are summarized. The review is organized by type of carriers including natural biomacromolecule (lipid, chitosan, cyclodextrin, etc.); synthetic polymer (poly(lactic-co-glycolic acid), polyethyleneimine, brush copolymer, etc.); mesoporous silica; gold nanoparticles; and others. Co-delivery of SF and other active agents (glypican-3, hyaluronic acid, apolipoprotein peptide, folate, and superparamagnetic iron oxide nanoparticles) for targeted SF nanosystems and synergistic drug combinations are also highlighted. All these studies showed promising results for targeted treatment of HCC and other cancers by SF-based nanomedicines. The outlook, challenges and future opportunities for the development of SF-based drug delivery are presented. Full article

Quercetin (QtN) displays low systemic bioavailability caused by poor water solubility and instability. Consequently, it exerts limited anticancer action in vivo. One solution to increase the anticancer efficacy of QtN is the use of appropriate functionalized nanocarriers that preferentially target and deliver the drug to the tumor location. Herein, a direct advanced method was designed to develop water-soluble hyaluronic acid (HA)-QtN-conjugated silver nanoparticles (AgNPs). HA-QtN reduced silver nitrate (AgNO₃) while acting as a stabilizing agent to produce AgNPs. Further, HA-QtN#AgNPs served as an anchor for folate/folic acid (FA) conjugated with polyethylene glycol (PEG). The resulting PEG-FA-HA-QtN#AgNPs (further abbreviated as PF/HA-QtN#AgNPs) were characterized both in vitro and ex vivo. Physical characterizations included UV-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), particle size (PS) and zeta potential (ZP) measurements, and biopharmaceutical evaluations. The biopharmaceutical evaluations included analyses of the cytotoxic effects on the HeLa and Caco-2 cancer cell lines using the MTT assay; cellular drug intake into cancer cells using flow cytometry and confocal microscopy; and blood compatibility using an automatic hematology analyzer, a diode array spectrophotometer, and an enzyme-linked immunosorbent assay (ELISA). The prepared hybrid delivery nanosystem was hemocompatible and more oncocytotoxic than the free, pure QtN. Therefore, PF/HA-QtN#AgNPs represent a smart nano-based drug delivery system (NDDS) and could be a promising oncotherapeutic option if the data are validated in vivo. Full article