Search results for: nano particle nanocomposites

Authors: Z. S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

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Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

Abstract:

Polymeric nanoparticles-based drug delivery systems and therapeutics have a great potential in the treatment of a numerous diseases, due to they are characterizing the flexible properties which is giving possibility to modify their structures with a complex definition over their structures, compositions and properties. Important characteristics of the polymeric nanoparticles (PNPs) used as drug carriers are high particle’s stability, high carrier capacity, feasibility of encapsulation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, including oral application and inhalation; NPs are especially effective for intracellular drug delivery since they penetrate into the cells’ interior though endocytosis. A variety of PNPs based drug delivery systems including charged and neutral, degradable and non-degradable polymers of both natural and synthetic origin have been developed. Among these huge varieties the biodegradable PNPs which can be cleared from the body after the fulfillment of their function could be considered as one of the most promising. For intracellular uptake it is highly desirable to have positively charged PNPs since they can penetrate deep into cell membranes. For long-lasting circulation of PNPs in the body it is important they have so called “stealth coatings” to protect them from the attack of immune system of the organism. One of the effective ways to render the PNPs “invisible” for immune system is their PEGylation which represent the process of pretreatment of polyethylene glycol (PEG) on the surface of PNPs. The present work deals with constructing PNPs from amino acid based biodegradable polymers – regular poly(ester amide) (PEA) composed of sebacic acid, leucine and 1,6-hexandiol (labeled as 8L6), cationic PEA composed of sebacic acid, arginine and 1,6-hexandiol (labeled as 8R6), and comb-like co-PEA composed of sebacic acid, malic acid, leucine and 1,6-hexandiol (labeled as PEG-PEA). The PNPs were fabricated using the polymer deposition/solvent displacement (nanoprecipitation) method. The regular PEA 8L6 form stable negatively charged (zeta-potential within 2-12 mV) PNPs of desired size (within 150-200 nm) in the presence of various surfactants (Tween 20, Tween 80, Brij 010, etc.). Blending the PEAs 8L6 and 8R6 gave the 130-140 nm sized positively charged PNPs having zeta-potential within +20 ÷ +28 mV depending 8L6/8R6 ratio. The PEGylating PEA PEG-PEA was synthesized by interaction of epoxy-co-PEA [8L6]0,5-[tES-L6]0,5 with mPEG-amine-2000 The stable and positively charged PNPs were fabricated using pure PEG-PEA as a surfactant. A firm anchoring of the PEG-PEA with 8L6/8R6 based PNPs (owing to a high afinity of the backbones of all three PEAs) provided good stabilization of the NPs. In vitro biocompatibility study of the new PNPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed they are biocompatible. Considering high stability and cell compatibility of the elaborated PNPs one can conclude that they are promising for subsequent therapeutic applications. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 “New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications”.

Keywords: biodegradable poly(ester amide)s, cationic poly(ester amide), pegylating poly(ester amide), nanoparticles

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Authors: Farideh Namvar, Rosfarizan Mohamed

Abstract:

In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. This use of biological entities to create nanoparticles has designated as “Green” synthesis and it is considered to be far more beneficial due to being economical, eco-friendly and applicable for large-scale synthesis as it operates on low pressure, less input of energy and low temperatures. The lack of toxic byproducts and consequent decrease in degradation of the product renders this technique more preferable over physical and classical chemical methods. The variety of biomass having reduction properties to produce nanoparticles makes them an ideal candidate for fabrication. Metal oxide nanoparticles have been said to represent a "fundamental cornerstone of nanoscience and nanotechnology" due to their variety of properties and potential applications. However, this also provides evidence of the fact that metal oxides include many diverse types of nanoparticles with large differences in chemical composition and behaviour. In this study, iron oxide nanoparticles (Fe3O4-NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of ferric chloride solution with brown seaweed (Sargassum muticum) water extract containing polysaccharides as a main factor which acts as reducing agent and efficient stabilizer. Antimicrobial activity against six microorganisms was tested using well diffusion method. The resulting S-IONPs are crystalline in nature, with a cubic shape. The average particle diameter, as determined by TEM, was found to be 18.01 nm. The S-IONPs were efficiently inhibited the growth of Listeria monocytogenes, Escherichia coli and Candida species. Our favorable results suggest that S-IONPs could be a promising candidate for development of future antimicrobial therapies. The nature of biosynthesis and the therapeutic potential by S-IONPs could pave the way for further research on design of green synthesis therapeutic agents, particularly nanomedicine, to deal with treatment of infections. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial activity of these particles. Antioxidant activity of S-IONPs synthesized by green method was measured by ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (IC50= 1000µg) radical scavenging activity. Also, with the increasing concentration of S-IONPs, catalase gene expression compared to control gene GAPDH increased. For anti-angiogenesis study the Ross fertilized eggs were divided into four groups; the control and three experimental groups. The gelatin sponges containing albumin were placed on the chorioalantoic membrane and soaked with different concentrations of S-IONPs. All the cases were photographed using a photo stereomicroscope. The number and the lengths of the vessels were measured using Image J software. The crown rump (CR) and weight of the embryo were also recorded. According to the data analysis, the number and length of the blood vessels, as well as the CR and weight of the embryos reduced significantly compared to the control (p < 0.05), dose dependently. The total hemoglobin was quantified as an indicator of the blood vessel formation, and in the treated samples decreased, which showed its inhibitory effect on angiogenesis.

Keywords: anti-angiogenesis, antimicrobial, antioxidant, biosynthesis, iron oxide (fe3o4) nanoparticles, sargassum muticum, seaweed

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Authors: Juergen Orasche, Vesta Kohlmeier, George C. Dragan, Gert Jakobi, Patricia Forbes, Ralf Zimmermann

Abstract:

Underground mining poses a difficult environment for both man and machines. At more than 1000 meters underneath the surface of the earth, ores and other mineral resources are still gained by conventional and motorised mining. Adding to the hazards caused by blasting and stone-chipping, the working conditions are best described by the high temperatures of 35-40°C and high humidity, at low air exchange rates. Separate ventilation shafts lead fresh air into a mine and others lead expended air back to the surface. This is essential for humans and machines working deep underground. Nevertheless, mines are widely ramified. Thus the air flow rate at the far end of a tunnel is sensed to be close to zero. In recent years, conventional mining was supplemented by mining with heavy diesel machines. These very flat machines called Load Haul Dump (LHD) vehicles accelerate and ease work in areas favourable for heavy machines. On the other hand, they emit non-filtered diesel exhaust, which constitutes an occupational hazard for the miners. Combined with a low air exchange, high humidity and inorganic dust from the mining it leads to 'black smog' underneath the earth. This work focuses on the air quality in mines employing LHDs. Therefore we performed personal sampling (samplers worn by miners during their work), stationary sampling and aethalometer (Microaeth MA200, Aethlabs) measurements in a platinum mine in around 1000 meters under the earth’s surface. We compared areas of high diesel exhaust emission with areas of conventional mining where no diesel machines were operated. For a better assessment of health risks caused by air pollution we applied a separated gas-/particle-sampling tool (or system), with first denuder section collecting intermediate VOCs. These multi-channel silicone rubber denuders are able to trap IVOCs while allowing particles ranged from 10 nm to 1 µm in diameter to be transmitted with an efficiency of nearly 100%. The second section is represented by a quartz fibre filter collecting particles and adsorbed semi-volatile organic compounds (SVOC). The third part is a graphitized carbon black adsorber – collecting the SVOCs that evaporate from the filter. The compounds collected on these three sections were analyzed in our labs with different thermal desorption techniques coupled with gas chromatography and mass spectrometry (GC-MS). VOCs and IVOCs were measured with a Shimadzu Thermal Desorption Unit (TD20, Shimadzu, Japan) coupled to a GCMS-System QP 2010 Ultra with a quadrupole mass spectrometer (Shimadzu). The GC was equipped with a 30m, BP-20 wax column (0.25mm ID, 0.25µm film) from SGE (Australia). Filters were analyzed with In-situ derivatization thermal desorption gas chromatography time-of-flight-mass spectrometry (IDTD-GC-TOF-MS). The IDTD unit is a modified GL sciences Optic 3 system (GL Sciences, Netherlands). The results showed black carbon concentrations measured with the portable aethalometers up to several mg per m³. The organic chemistry was dominated by very high concentrations of alkanes. Typical diesel engine exhaust markers like alkylated polycyclic aromatic hydrocarbons were detected as well as typical lubrication oil markers like hopanes.

Keywords: diesel emission, personal sampling, aethalometer, mining

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Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

Procedia PDF Downloads 52

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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