Ketoprofen-Based Polymer-Drug Nanoparticles Provide Anti-Inflammatory Properties to HA/Collagen Hydrogels.

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.

The Role of Polymeric Biomaterials in the Treatment of Articular Osteoarthritis.

Osteoarthritis is a high-prevalence joint disease characterized by the degradation of cartilage, subchondral bone thickening, and synovitis. Due to the inability of cartilage to self-repair, regenerative medicine strategies have become highly relevant in the management of osteoarthritis. Despite the great advances in medical and pharmaceutical sciences, current therapies stay unfulfilled, due to the inability of cartilage to repair itself. Additionally, the multifactorial etiology of the disease, including endogenous genetic dysfunctions and exogenous factors in many cases, also limits the formation of new cartilage extracellular matrix or impairs the regular recruiting of chondroprogenitor cells. Hence, current strategies for osteoarthritis management involve not only analgesics, anti-inflammatory drugs, and/or viscosupplementation but also polymeric biomaterials that are able to drive native cells to heal and repair the damaged cartilage. This review updates the most relevant research on osteoarthritis management that employs polymeric biomaterials capable of restoring the viscoelastic properties of cartilage, reducing the symptomatology, and favoring adequate cartilage regeneration properties.

Amphiphilic polymeric nanoparticles encapsulating curcumin: Antioxidant, anti-inflammatory and biocompatibility studies.

Oxidative stress and inflammation are two related processes common to many diseases. Curcumin is a natural compound with both antioxidant and anti-inflammatory properties, among others, that is recently being used as a natural occurring product alternative to traditional drugs. However, it has a hydrophobic nature that compromises its solubility in physiological fluids and its circulation time and also presents cytotoxicity problems in its free form, limiting the range of concentrations to be used. In order to overcome these drawbacks and taking advantage of the benefits of nanotechnology, the aim of this work is the development of curcumin loaded polymeric nanoparticles that can provide a controlled release of the drug and enlarge their application in the treatment of inflammatory and oxidative stress related diseases. Specifically, the vehicle is a bioactive terpolymer based on a α-tocopheryl methacrylate, 1-vinyl-2-pyrrolidone and N-vinylcaprolactam. Nanoparticles were obtained by nanoprecipitation and characterized in terms of size, morphology, stability, encapsulation efficiency and drug release. In vitro cellular assays were performed in human articular chondrocyte and RAW 264.7 cultures to assess cytotoxicity, cellular uptake, antioxidant and anti-inflammatory properties. The radical scavenging activity of the systems was confirmed by the DPPH test and the quantification of cellular reactive oxygen species. The anti-inflammatory potential of these systems was demonstrated by the reduction of different pro-inflammatory factors such as IL-8, MCP and MIP in chondrocytes; and nitric oxide, IL-6, TNF-α and MCP-1, among others, in RAW 264.7. Finally, the in vivo biocompatibility was confirmed in a rat model by subcutaneously injecting the nanoparticle dispersions. The reduction of curcumin toxicity and the antioxidant, anti-inflammatory and biocompatibility properties open the door to deeper in vitro and in vivo research on these curcumin loaded polymeric nanoparticles to treat inflammation and oxidative stress based diseases.

Oregano Essential Oil Micro- and Nanoencapsulation With Bioactive Properties for Biotechnological and Biomedical Applications.

Due to the preservative, antioxidant, antimicrobial, and therapeutic properties of oregano essential oil (OEO), it has received an emerging interest for biotechnological and biomedical applications. However, stability and bioactivity can be compromised by its natural volatile and hydrophobic nature, and by external factors including light, heat, or oxygen. Therefore, micro- and nanoencapsulation are being employed to guarantee oregano oil protection from outside aggressions and to maximize its potential. Oregano oil encapsulation is an interesting strategy used to increase its stability, enhance its bioactivity, and decrease its volatility. At the same time, the versatility that micro- and nanocarriers offer, allows to prepare tailored systems that can provide a controlled and targeted release of the encapsulated principle, influence its bioactive activities, or even provide additional properties. Most common materials used to prepare these carriers are based on lipids and cyclodextrins, due to their hydrophobic nature, polymers due to their versatility in composition, and hybrid lipid-polymer systems. In this context, recently developed micro- and nanocarriers encapsulating oregano oil with applications in the biotechnological and biomedical fields will be discussed.

Modulation of Inflammatory Mediators by Polymeric Nanoparticles Loaded with Anti-Inflammatory Drugs.

The first-line treatment of osteoarthritis is based on anti-inflammatory drugs, the most currently used being nonsteroidal anti-inflammatory drugs, selective cyclooxygenase 2 (COX-2) inhibitors and corticoids. Most of them present cytotoxicity and low bioavailability in physiological conditions, making necessary the administration of high drug concentrations causing several side effects. The goal of this work was to encapsulate three hydrophobic anti-inflammatory drugs of different natures (celecoxib, tenoxicam and dexamethasone) into core-shell terpolymer nanoparticles with potential applications in osteoarthritis. Nanoparticles presented hydrodynamic diameters between 110 and 130 nm and almost neutral surface charges (between -1 and -5 mV). Encapsulation efficiencies were highly dependent on the loaded drug and its water solubility, having higher values for celecoxib (39-72%) followed by tenoxicam (20-24%) and dexamethasone (14-26%). Nanoencapsulation reduced celecoxib and dexamethasone cytotoxicity in human articular chondrocytes and murine RAW264.7 macrophages. Moreover, the three loaded systems did not show cytotoxic effects in a wide range of concentrations. Celecoxib and dexamethasone-loaded nanoparticles reduced the release of different inflammatory mediators (NO, TNF-α, IL-1ß, IL-6, PGE2 and IL-10) by lipopolysaccharide (LPS)-stimulated RAW264.7. Tenoxicam-loaded nanoparticles reduced NO and PGE2 production, although an overexpression of IL-1ß, IL-6 and IL-10 was observed. Finally, all nanoparticles proved to be biocompatible in a subcutaneous injection model in rats. These findings suggest that these loaded nanoparticles could be suitable candidates for the treatment of inflammatory processes associated with osteoarthritis due to their demonstrated in vitro activity as regulators of inflammatory mediator production.

Characterization of Novel Synthetic Polyphenols: Validation of Antioxidant and Vasculoprotective Activities.

Antioxidant compounds, including polyphenols, have therapeutic effects because of their anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. They play important roles in protecting the cardiovascular and neurological systems, by having preventive or protective effects against free radicals produced by either normal or pathological metabolism in such systems. For instance, resveratrol, a well-known potent antioxidant, has a counteracting effect on the excess of reactive oxygen species (ROS) and has a number of therapeutic benefits, like anti-inflammatory, anti-cancer and cardioprotective activities. Based on previous work from our group, and on the most frequent OH substitutions of natural polyphenols, we designed two series of synthetically accessible bis-polyhydroxyphenyl derivatives, separated by amide or urea linkers. These compounds exhibit high antioxidant ability (oxygen radical absorbance capacity (ORAC) assay) and interesting radical scavenging activity (RSA) values (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and α,α-diphenyl-ß-picrylhydrazyl (DPPH) tests). Some of the best polyphenols were evaluated in two biological systems, endothelial cells (in vitro) and whole aorta (ex vivo), highly susceptible for the deleterious effects of prooxidants under different inflammatory conditions, showing protection against oxidative stress induced by inflammatory stimuli relevant in cardiovascular diseases, i.e., Angiotensin II and IL-1ß. Selected compounds also showed strong in vivo antioxidant properties when evaluated in the model organism Saccharomyces cerevisiae.

Active viscosupplements for osteoarthritis treatment.

OBJECTIVE: Osteoarthritis is a chronic, painful and disabling disease which prevalence is increasing in developing countries. Patients with osteoarthritis present a reduced synovial fluid viscoelasticity due to a reduction in concentration and molecular weight of hyaluronic acid. Currently, the main treatment used to restore the compromised rheological properties of synovial fluid is the viscosupplementation by hyaluronic acid injections that can be combined with oral anti-inflammatory drugs for pain relief. Combination of viscosupplements with chemical agents or drugs is emerging as a new strategy to provide a double action of synovial fluid viscoelasticity recovery and the therapeutic effect of the bioactive principle. METHODS: In this review, we present the latest research on the combination of viscosupplements with active molecules. We conducted a literature review of articles published in different web search engines and categorized according to the active molecule introduced into the viscosupplement. RESULTS: Generally, the introduction of anti-inflammatory molecules have shown to improve pain relief although some cytotoxicity has been demonstrated especially for non-steroidal anti-inflammatory drugs. Other molecules such as antioxidant or disease modifying osteoarthritis drugs have been reported to improve viscosupplementation action. Drug delivery systems combined with hyaluronic acid could enhance the activity of the encapsulated molecules and provide better control over the drug release. Finally, biological approaches such as the use of stem cells or platelet-rich plasma seem to be the most promising strategies for cartilage recovery. CONCLUSIONS: Combination therapy of viscosupplements with therapeutic agents, drug delivery systems or regenerative therapies can improve viscosupplementation outcome in terms of pain relief and joint functionality. However, further research is needed in order to reach more conclusive results.

Preparation and Characterization of Antimicrobial Films Based on LDPE/Ag Nanoparticles with Potential Uses in Food and Health Industries.

In this work, the antimicrobial effect of silver nanoparticles in polyethylene based nanocomposites has been investigated using a non-conventional processing method to produce homogeneous materials. High energy ball milling under cryogenic conditions was used to achieve a powder of well-blended low-density polyethylene and commercial silver nanoparticles. The final composites in the form of films were obtained by hot pressing. The effect of various silver nanoparticles content (0, 0.5, 1 and 2 wt %) on the properties of low-density polyethylene and the antimicrobial effectiveness of the composite against DH5α Escherichia coli were studied. The presence of silver nanoparticles did not seem to affect the surface energy and thermal properties of the materials. Apart from the inhibition of bacterial growth, slight changes in the aspect ratio of the bacteria with the content of particles were observed, suggesting a direct relationship between the presence of silver nanoparticles and the proliferation of DH5α E. coli (Escherichia coli) cells. Results indicate that these materials may be used to commercially produce antimicrobial polymers with potential applications in the food and health industries.