Nanoparticle-based model of anti-inflammatory drug releasing LbL coatings for uncemented prosthesis aseptic loosening prevention

Introduction: The only treatment for aseptic loosening is the replacement of the prosthesis through revision surgery. A preventive approach, achieved through anti-inflammatory drugs released from the device, has shown to be a viable strategy; however, the performance of these devices is not yet satisfactory thus further improvements are necessary.Methods: We used titanium nanoparticles as a model for implant surfaces and developed a coating containing dexamethasone (DEX) using layer-by-layer deposition.Results: The amount of deposited drug depended on the number of layers and the release was sustained for months. The efficiency of the released DEX in reducing inflammation markers (tumor necrosis factor alpha and IL-6) produced by human monocytes and macrophages was similar to the pure drug at the same concentration without negative impacts on the viability and morphology of these cells.Conclusion: These coatings were not inferior to medical grade titanium (the standard material used in uncemented devices) regarding their ability to sustain osteoblasts and fibroblasts growth

PMMA bone cement containing long releasing silica-based chlorhexidine nanocarriers

Prosthetic joint infections (PJI) are still an extremely concerning eventuality after joint replacement surgery; growing antibiotic resistance is also limiting the prophylactic and treatment options. Chlorhexidine (a widely used topical non-antibiotic antimicrobial compound) coatings on silica nanoparticles capable of prolonged drug release have been successfully developed and characterised. Such nanocarriers were incorporated into commercial formulation PMMA bone cement (Cemex), without adversely affecting the mechanical performance. Moreover, the bone cement containing the developed nanocarriers showed superior antimicrobial activity against different bacterial species encountered in PJI, including clinical isolates already resistant to gentamicin. Cytocompatibility tests also showed non inferior performance of the bone cements containing chlorhexidine releasing silica nanocarriers to the equivalent commercial formulation

Sunlight induced synthesis of silver nanoparticles on cellulose for the preparation of antimicrobial textiles

Antibiotic resistance is a major threat to heath with the use of silver nanoparticles as a possible approach; however, the synthetic routes of such nanomaterials are not environmentally friendly because of the chemicals required. In this work we approach both problems with a single solution that employs sunlight in the visible spectrum to prepare nanosilver on the surface of cotton fabrics soaked in a solution of silver nitrate. Photoactivation leads to the activation of aldehyde groups providing reducing ability to cellulose and enabling the formation of elemental silver without the use of any chemical reducing agents. Concentrations of silver nitrate solution of 30 g/L reached the saturation of the content of elemental silver on fabric at 52.8 mg/dm2. SEM images showed that silver particles were evenly distributed in fabric in the form of spherical particles 100–600 nm in diameter. The materials exhibited antimicrobial properties against E. coli and S. aureus retaining such properties after repeated washings. Moreover, no adverse effects were observed on fibroblast cells exposed to the prepared textiles

Polymer colloids as drug delivery systems for the treatment of arthritis

The most common types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA) which are themain causes of disability and pain among older people. Current treatment of arthritis mainly consists of oral and intra-articular medications. Despite the efficacy of the intraarticular injections over the oral treatment, it is still limited by the rapid clearance of the injected drug. Therefore, a rational design of drug delivery systems (DDSs) able to delivery drugs in controlled manner and for required period of time to the arthritis joint is a key in developing safe and effective formulations for OA and RA. In this paper various colloidal systems like nanoparticles, liposomes, cationic carriers, hydrogels, and emulsion-based carriers were presented and discussed in light of their use and efficacy as delivery systems to transport therapeutics for arthritis treatment. Factors influencing the delivery efficacy such as size, charge, structure, drug uptake, retention and its release profile alongside with cytocompatibility and safety were addressed. Moreover, the advantages and disadvantages of the different colloidal systems were emphasised

Vardenafil-Loaded Bilosomal Mucoadhesive Sponge for Buccal Delivery: Optimization, Characterization, and In Vivo Evaluation

Vardenafil (VDF) is a relatively new phosphodiesterase-5 inhibitor that has limited oral bioavailability (≈15%). The objective of this study was to develop bilosome-based mucoadhesive buccal sponge for augmenting the oral bioavailability of VDF. VDF-loaded bilosomes were fabricated and optimized using a Box-Behnken design. The optimized VDF-loaded bilosomal formulation was assessed for surface morphology, particle size, thermal characteristics, and in vitro release. Afterwards, the optimized bilosomal formulation was incorporated into a cellulose-based matrix to obtain buccal sponge, which was evaluated for ex vivo permeation studies, in vivo oral bioavailability, and in vivo serum concentration of cyclic guanosine monophosphate (cGMP). The mean particle size and entrapment efficiency (%) of optimized bilosome formulation were 282.6 ± 9.5 nm and 82.95 ± 3.5%, respectively. In vitro release studies at pH 6.8 emphasized the potential of optimized bilosomal formulation to sustain VDF release for 12 h. Ex vivo permeation study using sheep buccal mucosa indicated significant enhancement in penetration of VDF from bilosomal buccal sponge compared to plain VDF gel. Pharmacokinetic study in Albino rats showed ~5 fold increase in relative bioavailability with bilosomal buccal sponge, compared to VDF suspension. In addition, VDF-loaded bilosomal buccal sponge triggered higher serum levels of cGMP, a biomarker of VDF in vivo efficacy, compared to oral VDF suspension. To sum up, bilosomes might represent a potential nanocarrier for buccal delivery of VDF, enhancing its oral bioavailability and therapeutic efficacy

Cytotoxic and Apoptotic Effect of Rubus chingii Leaf Extract against Non-Small Cell Lung Carcinoma A549 Cells

Rubus chingii is a traditional Chinese medicinal herbal that has been used since ancient times for its great dietary and medicinal values. Recent reports have underscored the promising cytotoxic effect of R. chingii extracts against a wide variety of cancer cells. Therefore, in the current study, we aim to explore the anticancer potential of the Rubus chingii ethanolic leaf extract (RcL-EtOH) against non-small cell lung cancer A549 cells. RcL-EtOH efficiently exerted a cytotoxic effect against A549 cells in a dose dependent manner, whilst, it exhibited non-significant toxic effects on normal murine macrophage cells, signifying its safety against normal cells. The reduced viability of A549 cells was reaffirmed by the acridine orange/ethidium bromide double staining, which confirmed the induction of apoptosis in RcL-EtOH-treated A549 cells. In addition, RcL-EtOH instigated the dissipation of mitochondrial membrane potential (ΔΨm) with mutual escalation in ROS generation in a dose-dependent manner. Furthermore, RcL-EtOH increased caspase-3, caspase-9 levels in A549 cells post-exposure to RcL-EtOH, which was concomitantly followed by altered mRNA expression of apoptotic (anti-apoptotic: Bcl-2, BclXL; pro-apoptotic: Bax, Bad). To sum up, the RcL-EtOH-instigated apoptotic cell death within A549 cells was assumed to be accomplished via targeting mitochondria, triggering increased ROS generation, with subsequent activation of caspase cascade and altering the expression of gene regulating apoptosis. Collectively, RcL-EtOH might represent a plausible therapeutic option for the management of lung cancer

Terazosin Interferes with Quorum Sensing and Type Three Secretion System and Diminishes the Bacterial Espionage to Mitigate the Salmonella Typhimurium Pathogenesis

Salmonella enterica is an invasive intracellular pathogen and hires diverse systems to manipulate its survival in the host cells. Salmonella could eavesdrop on the host cells, sensing and responding to the produced adrenergic hormones and other neurotransmitters, which results in the augmentation of its virulence and establishes its accommodation in host cells. The current study aims to assess the anti-virulence effect of α-adrenergic antagonist terazosin on S. Typhimurium. Our findings show that terazosin significantly reduced S. Typhimurium adhesion and biofilm formation. Furthermore, terazosin significantly decreased invasion and intracellular replication of S. Typhimurium. Interestingly, in vivo, terazosin protected the mice from S. Typhimurium pathogenesis. To understand the terazosin anti-virulence activity, its effect on quorum sensing (QS), bacterial espionage, and type three secretion system (T3SS) was studied. Strikingly, terazosin competed on the membranal sensors that sense adrenergic hormones and down-regulated their encoding genes, which indicates the ability of terazosin to diminish the bacterial eavesdropping on the host cells. Moreover, terazosin significantly reduced the Chromobacterium violaceum QS-controlled pigment production and interfered with the QS receptor Lux-homolog Salmonella SdiA, which indicates the possible terazosin-mediated anti-QS activity. Furthermore, terazosin down-regulated the expression of T3SS encoding genes. In conclusion, terazosin may mitigate S. Typhimurium virulence owing to its hindering QS and down-regulating T3SS encoding genes besides its inhibition of bacterial espionage

Long acting anti-infection constructs on titanium

Peri-prosthetic joint infections (PJI) are a serious adverse event following joint replacement surgeries; antibiotics are usually added to bone cement to prevent infection offset. For uncemented prosthesis, alternative antimicrobial approaches are necessary in order to prevent PJI; however, despite elution of drug from the surface of the device being shown one of the most promising approach, no effective antimicrobial eluting uncemented device is currently available on the market. Consequently, there is a clinical need for non-antibiotic antimicrobial uncemented prosthesis as these devices present numerous benefits, particularly for young patients, over cemented artificial joints. Moreover, non-antibiotic approaches are driven by the need to address the growing threat posed by antibiotic resistance. We developed a multilayers functional coating on titanium surfaces releasing chlorhexidine, a well-known antimicrobial agent used in mouthwash products and antiseptic creams, embedding the drug between alginate and poly-beta-amino-esters. Chlorhexidine release was sustained for almost 2 months and the material efficacy and safety was proven both in vitro and in vivo. The coatings did not negatively impact osteoblast and fibroblast cells growth and were capable of reducing bacterial load and accelerating wound healing in an excisional wound model. As PJI can develop weeks and months after the initial surgery, these materials could provide a viable solution to prevent infections after arthroplasty in uncemented prosthetic devices and, simultaneously, help the fight against antibiotic resistance

Terazosin Interferes with Quorum Sensing and Type Three Secretion System and Diminishes the Bacterial Espionage to Mitigate the <i>Salmonella</i> Typhimurium Pathogenesis

Salmonella enterica is an invasive intracellular pathogen and hires diverse systems to manipulate its survival in the host cells. Salmonella could eavesdrop on the host cells, sensing and responding to the produced adrenergic hormones and other neurotransmitters, which results in the augmentation of its virulence and establishes its accommodation in host cells. The current study aims to assess the anti-virulence effect of α-adrenergic antagonist terazosin on S. Typhimurium. Our findings show that terazosin significantly reduced S. Typhimurium adhesion and biofilm formation. Furthermore, terazosin significantly decreased invasion and intracellular replication of S. Typhimurium. Interestingly, in vivo, terazosin protected the mice from S. Typhimurium pathogenesis. To understand the terazosin anti-virulence activity, its effect on quorum sensing (QS), bacterial espionage, and type three secretion system (T3SS) was studied. Strikingly, terazosin competed on the membranal sensors that sense adrenergic hormones and down-regulated their encoding genes, which indicates the ability of terazosin to diminish the bacterial eavesdropping on the host cells. Moreover, terazosin significantly reduced the Chromobacterium violaceum QS-controlled pigment production and interfered with the QS receptor Lux-homolog Salmonella SdiA, which indicates the possible terazosin-mediated anti-QS activity. Furthermore, terazosin down-regulated the expression of T3SS encoding genes. In conclusion, terazosin may mitigate S. Typhimurium virulence owing to its hindering QS and down-regulating T3SS encoding genes besides its inhibition of bacterial espionage