Search Results (26)

Nanogels are polymer-based, crosslinked hydrogel particles on the nanometer scale. Nanogels developed from synthetic and natural polymers have gathered a great deal of attention in industry and scientific society due to having an increased surface area, softness, flexibility, absorption, and drug loading ability, as well as their mimicking the environment of a tissue. Nanogels having biocompatibility, nontoxic and biodegradable properties with exceptional design, fabrication, and coating facilities may be used for a variety of different biomedical applications, such as drug delivery and therapy, tissue engineering, and bioimaging. Nanogels fabricated by chemical crosslinking and physical self-assembly displayed the ability to encapsulate therapeutics, including hydrophobic, hydrophilic, and small molecules, proteins, peptides, RNA and DNA sequences, and even ultrasmall nanoparticles within their three-dimensional polymer networks. One of the many drug delivery methods being investigated as a practical option for targeted delivery of drugs for cancer treatment is nanogels. The delivery of DNA and anticancer drugs like doxorubicin, epirubicin, and paclitaxel has been eased by polymeric nanogels. Stimuli-responsive PEGylated nanogels have been reported as smart nanomedicines for cancer diagnostics and therapy. Another promising biomedical application of nanogels is wound healing. Wounds are injuries to living tissue caused by a cut, blow, or other impact. There are numerous nanogels having different polymer compositions that have been reported to enhance the wound healing process, such as hyaluronan, poly-L-lysine, and berberine. When antimicrobial resistance is present, wound healing becomes a complicated process. Researchers are looking for novel alternative approaches, as foreign microorganisms in wounds are becoming resistant to antibiotics. Silver nanogels have been reported as a popular antimicrobial choice, as silver has been used as an antimicrobial throughout a prolonged period. Lignin-incorporated nanogels and lidocaine nanogels have also been reported as an antioxidant wound-dressing material that can aid in wound healing. In this review, we will summarize recent progress in biomedical applications for various nanogels, with a prime focus on cancer and wound healing. Full article

Lipid nanoparticles (LNPs) have established their position as nonviral vectors for gene therapy. Tremendous efforts have been made to modulate the properties of LNPs to unleash their full clinical potential. Among the strategies being pursued, the layer-by-layer (LbL) technique has gained considerable attention in the biomedical field. Illuminated by our previous work, here we investigate if the LbL approach could be used to modify the LNP cores formulated with three different ionizable lipids: DODMA, MC3, and DODAP. Additionally, we wondered if more than three layers could be loaded onto LNPs without disrupting their gene transfection ability. Taking advantage of physicochemical analysis, as well as uptake and gene silencing studies, we demonstrate the feasibility of modifying the surface of LNPs with the LbL assembly. Precisely, we successfully modified three different LNPs using the layer-by-layer strategy which abrogated luciferase activity in vitro. Additionally, we constructed a 5×-layered HA-LNP containing the MC3 ionizable lipid which outperformed the 3×-layered counterpart in transfecting miRNA-181-5p to the pediatric GBM cell line, as a proof-of-concept in vitro experiment. The method used herein has been proven reproducible, of easy modification to adapt to different ionizable lipid-containing LNPs, and holds great potential for the translation of RNA-based therapeutic strategies. Full article

Hyaluronic acid (HA) is a linear, anionic, non-sulfated glycosaminoglycan occurring in almost all body tissues and fluids of vertebrates including humans. It is a main component of the extracellular matrix and, thanks to its high water-holding capacity, plays a major role in tissue hydration and osmotic pressure maintenance, but it is also involved in cell proliferation, differentiation and migration, inflammation, immunomodulation, and angiogenesis. Based on multiple physiological effects on tissue repair and reconstruction processes, HA has found extensive application in regenerative medicine. In recent years, nanotechnological research has been applied to HA in order to improve its regenerative potential, developing nanomedical formulations containing HA as the main component of multifunctional hydrogels systems, or as core component or coating/functionalizing element of nanoconstructs. This review offers an overview of the various uses of HA in regenerative medicine aimed at designing innovative nanostructured devices to be applied in various fields such as orthopedics, dermatology, and neurology. Full article

Current limitations of wound dressings for treating chronic wounds require the development of novel approaches. One of these is the immune-centered approach, which aims to restore the pro-regenerative and anti-inflammatory properties of macrophages. Under inflammatory conditions, ketoprofen nanoparticles (KT NPs) can reduce pro-inflammatory markers of macrophages and increase anti-inflammatory cytokines. To assess their suitability as part of wound dressings, these NPs were combined with hyaluronan (HA)/collagen-based hydro- (HGs) and cryogels (CGs). Different HA and NP concentrations and loading techniques for NP incorporation were used. The NP release, gel morphology, and mechanical properties were studied. Generally, colonialization of the gels with macrophages resulted in high cell viability and proliferation. Furthermore, direct contact of the NPs to the cells reduced the level of nitric oxide (NO). The formation of multinucleated cells on the gels was low and further decreased by the NPs. For the HGs that produced the highest reduction in NO, extended ELISA studies showed reduced levels of the pro-inflammatory markers PGE2, IL-12 p40, TNF-α, and IL-6. Thus, HA/collagen-based gels containing KT NPs may represent a novel therapeutic approach for treating chronic wounds. Whether effects observed in vitro translate into a favorable profile on skin regeneration in vivo will require rigorous testing. Full article

In the last years, nanoparticles based on cyclodextrins have been widely investigated for the delivery of anticancer drugs. In this work, we synthesized nanoparticles with a hyaluronic acid backbone functionalized with cyclodextrins under green conditions. We functionalized hyaluronic acid with two different molecular weights (about 11 kDa and 45 kDa) to compare their behavior as doxorubicin delivery systems. We found that the new hyaluronan-cyclodextrin conjugates increased the water solubility of doxorubicin. Moreover, we tested the antiproliferative activity of doxorubicin in the presence of the new cyclodextrin polymers in SK-N-SH and SK-N-SH-PMA (over-expressing CD44 receptor) cancer cells. We found that hyaluronan-cyclodextrin conjugates improved the uptake and antiproliferative activity of doxorubicin in the SK-N-SH-PMA compared to the SK-N-SH cell line at the ratio 8/1 doxorubicin/polymer. Notably, the system based on hyaluronan (45 kDa) was more effective as a drug carrier and significantly reduced the IC₅₀ value of doxorubicin by about 56%. We also found that hyaluronic acid polymers determined an improved antiproliferative activity of doxorubicin (IC₅₀ values are on average reduced by about 70% of free DOXO) in both cell lines at the ratio 16/1 doxorubicin/polymer. Full article

Hyaluronan (HA) plays a fundamental role in maintaining the homeostasis on skin health. Furthermore, the effect of HA in skin inflammatory diseases is worth studying in the next future. HA and its conjugates change the solubility of active pharmaceutical ingredients, improve emulsion properties, prolong stability, reduce immunogenicity, and provide targeting. HA penetrates to deeper layers of the skin via several mechanisms, which depend on the macromolecular structure and composition of the formulation. The cellular and molecular mechanisms involved in epidermal dysfunction and skin aging are not well understood. Nevertheless, HA is known to selectively activate CD44-mediated keratinocyte signaling that regulates its proliferation, migration, and differentiation. The molecular size of HA is critical for molecular mechanisms and interactions with receptors. High molecular weight HA is used in emulsions and low molecular weight is used to form nanostructured lipid carriers, polymeric micelles, bioconjugates, and nanoparticles. In the fabrication of microneedles, HA is combined with other polymers to enhance mechanical properties for piercing the skin. Hence, this review aims to provide an overview of the current state of the art and last reported ways of processing, and applications in skin drug delivery, which will advocate for their broadened use in the future. Full article

Otitis externa, also known as outer ear infection, is a frequent affliction in both humans and animals. The most prevalent treatment for otitis externa is ear drops, but it is difficult to adhere properly to this treatment, causing poor patient compliance and the potential for complications. As a result, we have developed a tetraethyl orthosilicate-based hydrogel for use as single application treatment for otitis externa to increase ease of use and improve patient outcomes. Herein, we investigated the manufacturability of the hydrogel, focusing on several key aspects: formulation repeatability and reproducibility, material source and tolerances, release of a variety of model drugs, and impact of application-specific physiological factors, specifically local pH and enzymatic activity on drug release. Overall, our results indicate that these hydrogels are well suited for production and scalability, as they have a robust manufacturing process, have a wide tolerance for pH level, release a variety of model drugs, and are not impacted by outer ear canal-specific physiological factors. Full article

This study aims to develop specific-molecular-weight hyaluronic acid oligosaccharides-coated paclitaxel-loaded casein nanoparticles (HA-PT-Cas NPs) via chemical conjugation to increase the stability and antitumor effects. Optimized HA-PT-Cas NPs (HA/casein of 3:1) were obtained with a mean size of 235.3 nm and entrapment efficiency of 93.1%. HA-PT-Cas exhibited satisfactory stability at 4 °C for 12 days and 37 °C for 3 h; paclitaxel was retained at rates of 81.4% and 64.7%, respectively, significantly higher than those of PT-Cas (only 27.8% at 4 °C after 16 h and 20.3% at 37 °C after 3 h). HA-PT-Cas exhibited high efficiency (61.3%) in inhibiting A375 tumor owing to the enhanced stability of HA oligosaccharides barrier, which was comparable with that of 10 μg/mL cis-platinum (64.9%). Mice experiments showed the 74.6% tumor inhibition of HA-PT-Cas by intravenously administration, significantly higher than that of PT-casein (39.8%). Therefore, this work provides an effective carrier for drug delivery via HA oligomers-coated modification. Full article

Extracellular vesicles (EVs) function as conveyors of fatty acids (FAs) and other bioactive lipids and can modulate the gene expression and behavior of target cells. EV lipid composition influences the fluidity and stability of EV membranes and reflects the availability of lipid mediator precursors. Fibroblast-like synoviocytes (FLSs) secrete EVs that transport hyaluronic acid (HA). FLSs play a central role in inflammation, pannus formation, and cartilage degradation in joint diseases, and EVs have recently emerged as potential mediators of these effects. The aim of the present study was to follow temporal changes in HA and EV secretion by normal FLSs, and to characterize the FA profiles of FLSs and EVs during proliferation. The methods used included nanoparticle tracking analysis, confocal laser scanning microscopy, sandwich-type enzyme-linked sorbent assay, quantitative PCR, and gas chromatography. The expression of hyaluronan synthases 1–3 in FLSs and HA concentrations in conditioned media decreased during cell proliferation. This was associated with elevated proportions of 20:4n-6 and total n-6 polyunsaturated FAs (PUFAs) in high-density cells, reductions in n-3/n-6 PUFA ratios, and up-regulation of cluster of differentiation 44, tumor necrosis factor α, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ. Compared to the parent FLSs, 16:0, 18:0, and 18:1n-9 were enriched in the EV fraction. EV counts decreased during cell growth, and 18:2n-6 in EVs correlated with the cell count. To conclude, FLS proliferation was featured by increased 20:4n-6 proportions and reduced n-3/n-6 PUFA ratios, and FAs with a low degree of unsaturation were selectively transferred from FLSs into EVs. These FA modifications have the potential to affect membrane fluidity, biosynthesis of lipid mediators, and inflammatory processes in joints, and could eventually provide tools for translational studies to counteract cartilage degradation in inflammatory joint diseases. Full article

In the present study, we developed chitosan/hyaluronan nanoparticles (CS/HY NPs) for tumor targeting with vinblastine sulfate (VBL), that can be directed to the CD44 transmembrane receptor, over-expressed in cancer cells. NPs were prepared by coating with HY-preformed chitosan/tripolyphosphate (CS/TPP) NPs, or by polyelectrolyte complexation of CS with HY. NPs with a mean hydrodynamic radius (R_H) of 110 nm, 12% polydispersity index and negative zeta potential values were obtained by a direct complexation process. Transmission Electron Microscopy (TEM) images showed spherical NPs with a non-homogeneous matrix, probably due to a random localization of CS and HY interacting chains. The intermolecular interactions occurring between CS and HY upon NPs formation were experimentally evidenced by micro-Raman (µ-Raman) spectroscopy, through the analysis of the spectral changes of characteristic vibrational bands of HY during NP formation, in order to reveal the involvement of specific chemical groups in the process. Optimized NP formulation efficiently encapsulated VBL, producing a drug sustained release for 20 h. In vitro studies demonstrated a fast internalization of labeled CS/HY NPs (within 6 h) on K-562 human myeloid leukemia cells. Pre-saturation of CD44 by free HY produced a slowing-down of NP uptake over 24 h, demonstrating the need of CD44 for the internalization of HY-based NPs. Full article

While hyaluronic acid encapsulating superparamagnetic iron oxide nanoparticles have been reported to exhibit selective cytotoxicity toward cancer cells, it is unclear whether low-molecular-weight hyaluronic acid-conjugated superparamagnetic iron oxide nanoparticles also display such cytotoxicity. In this study, high-molecular-weight hyaluronic acid was irradiated with γ-ray, while Fe₃O₄ nanoparticles were fabricated using chemical co-precipitation. The low-molecular-weight hyaluronic acid and Fe₃O₄ nanoparticles were then combined according to a previous study. Size distribution, zeta potential, and the binding between hyaluronic acid and iron oxide nanoparticles were examined using dynamic light scattering and a nuclear magnetic resonance spectroscopy. The ability of the fabricated low-molecular-weight hyaluronic acid conjugated superparamagnetic iron oxide nanoparticles to target cancer cells was examined using time-of-flight secondary ion mass spectrometry and T2* weighted magnetic resonance images to compare iron signals in U87MG human glioblastoma and NIH3T3 normal fibroblast cell lines. Comparison showed that the present material could target U87MG cells at a higher rate than NIH3T3 control cells, with a viability inhibition rate of 34% observed at day two and no cytotoxicity observed in NIH3T3 normal fibroblasts during the three-day experimental period. Supported by mass spectrometry images confirming that the nanoparticles accumulated on the surface of cancer cells, the fabricated materials can reasonably be suggested as a candidate for both magnetic resonance imaging applications and as an injectable anticancer agent. Full article

Osteoarthritis (OA) is a joint disorder characterized by the progressive degeneration of articular cartilage. The phenotype and metabolism behavior of chondrocytes plays crucial roles in maintaining articular cartilage function. Chondrocytes dedifferentiate and lose their cartilage phenotype after successive subcultures or inflammation and synthesize collagen I and X (COL I and COL X). Farnesol, a sesquiterpene compound, has an anti-inflammatory effect and promotes collagen synthesis. However, its potent restoration effects on differentiated chondrocytes have seldom been evaluated. The presented study investigated farnesol’s effect on phenotype restoration by examining collagen and glycosaminoglycan (GAG) synthesis from dedifferentiated chondrocytes. The results indicated that chondrocytes gradually dedifferentiated through cellular morphology change, reduced expressions of COL II and SOX9, increased the expression of COL X and diminished GAG synthesis during four passages of subcultures. Pure farnesol and hyaluronan-encapsulated farnesol nanoparticles promote COL II synthesis. GAG synthesis significantly increased 2.5-fold after a farnesol treatment of dedifferentiated chondrocytes, indicating the restoration of chondrocyte functions. In addition, farnesol drastically increased the synthesis of COL II (2.5-fold) and GAG (15-fold) on interleukin-1β-induced dedifferentiated chondrocytes. A significant reduction of COL I, COL X and proinflammatory cytokine prostaglandin E2 was observed. In summary, farnesol may serve as a therapeutic agent in OA treatment. Full article

Carbon nanofibers (CNFs) are one-dimensional nanomaterials with excellent physical and broad-spectrum antimicrobial properties characterized by a low risk of antimicrobial resistance. Silver nanoparticles (AgNPs) are antimicrobial metallic nanomaterials already used in a broad range of industrial applications. In the present study these two nanomaterials were characterized by Raman spectroscopy, transmission electron microscopy, zeta potential, and dynamic light scattering, and their biological properties were compared in terms of cytotoxicity, proliferation, and gene expression in human keratinocyte HaCaT cells. The results showed that both AgNPs and CNFs present similar time-dependent cytotoxicity (EC₅₀ of 608.1 µg/mL for CNFs and 581.9 µg/mL for AgNPs at 24 h) and similar proliferative HaCaT cell activity. However, both nanomaterials showed very different results in the expression of thirteen genes (superoxide dismutase 1 (SOD1), catalase (CAT), matrix metallopeptidase 1 (MMP1), transforming growth factor beta 1 (TGFB1), glutathione peroxidase 1 (GPX1), fibronectin 1 (FN1), hyaluronan synthase 2 (HAS2), laminin subunit beta 1 (LAMB1), lumican (LUM), cadherin 1 CDH1, collagen type IV alpha (COL4A1), fibrillin (FBN), and versican (VCAN)) treated with the lowest non-cytotoxic concentrations in the HaCaT cells after 24 h. The AgNPs were capable of up-regulating only two genes (SOD1 and MMP1) while the CNFs were very effective in up-regulating eight genes (FN1, MMP1, CAT, CDH1, COL4A1, FBN, GPX1, and TGFB1) involved in the defense mechanisms against oxidative stress and maintaining and repairing tissues by regulating cell adhesion, migration, proliferation, differentiation, growth, morphogenesis, and tissue development. These results demonstrate CNF nanomaterials’ unique great potential in biomedical applications such as tissue engineering and wound healing. Full article

Intravitreal injections are clinically established procedures in the treatment of posterior eye diseases, such as wet age-related macular degeneration (wet AMD) which requires monthly intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) protein drugs that can lead to complications due to frequent dosing. In this study, we designed a composite drug delivery system (DDS) consisting of drug-loaded poly (lactide–co–glycolide) (PLGA) nanoparticles and a chemically crosslinked hyaluronan hydrogel to reduce the dosing frequency. The morphology, size, composition, and drug loading efficiency of the prepared nanoparticles were characterized. The properties of the modified hyaluronan polymers used were also examined. The degree of swelling/degradation and controlled release ability of the hyaluronan hydrogel and the composite DDS were identified using bovine serum albumin (BSA) as a model drug. The results show that this system can retain 75% of its wet weight without losing its integrity and release the model drug at the rate of 0.4 μg/day for more than two months under physiological conditions. In addition, the nanoparticulate formulation of the system can further improve bioavailability of the drugs by penetrating deep into the retinal layers. In conclusion, the proposed composite DDS is easily prepared with biocompatible materials and is promising for providing the sustained release of the protein drugs as a better treatment for ocular neovascular diseases like wet AMD. Full article

Osteoarthritis (OA) remains one of the common degenerative joint diseases and a major cause of pain and disability in older adult individuals. Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) (such as diclofenac, DIC) or intra-articular injected gluco-corticosteroids (such as dexamethasone, DEX) were the conventional treatment strategies for OA to reduce joint pain. Current limitations for both drugs including severe adverse effects with risks of toxicity were noted. The aim of the present study was to generate a novel OA treatment formulation hyaluronic acid (HA)-Liposomal (Lipo)-DIC/DEX to combat joint pain. The formulation was prepared by constructing DIC with DEX-loaded nanostructured lipid carriers Lipo-DIC/DEX mixed with hyaluronic acid (HA) for prolonged OA application. The prepared Lipo-DIC/DEX nanoparticles revealed the size as 103.6 ± 0.3 nm on average, zeta potential as −22.3 ± 4.6 mV, the entrapment efficiency of 90.5 ± 5.6%, and the DIC and DEX content was 22.5 ± 4.1 and 2.5 ± 0.6%, respectively. Evidence indicated that HA-Lipo-DIC/DEX could reach the effective working concentration in 4 h and sustained the drug-releasing time for at least 168 h. No significant toxicities but increased cell numbers were observed when HA-Lipo-DIC/DEX co-cultured with articular chondrocytes cells. Using live-animal In vivo imaging system (IVIS), intra-articular injection of each HA-Lipo-DIC/DEX sufficed to reduce knee joint inflammation in OA mice over a time span of four weeks. Single-dose injection could reduce the inflammation volume down to 77.5 ± 5.1% from initial over that time span. Our results provided the novel drug-releasing formulation with safety and efficiency which could be a promising system for osteoarthritis pain control. Full article