Search results for: lost sale rate

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 79

Authors: Ali Kadir, S. R. Mishra, M. Shamshuddin, O. Anwar Beg

Abstract:

Motivation- Rotating disk bio-reactors are fundamental to numerous medical/biochemical engineering processes including oxygen transfer, chromatography, purification and swirl-assisted pumping. The modern upsurge in biologically-enhanced engineering devices has embraced new phenomena including bioconvection of micro-organisms (photo-tactic, oxy-tactic, gyrotactic etc). The proven thermal performance superiority of nanofluids i.e. base fluids doped with engineered nanoparticles has also stimulated immense implementation in biomedical designs. Motivated by these emerging applications, we present a numerical thermofluid dynamic simulation of the transport phenomena in bioconvection nanofluid rotating disk bioreactor flow. Methodology- We study analytically and computationally the time-dependent three-dimensional viscous gyrotactic bioconvection in swirling nanofluid flow from a rotating disk configuration. The disk is also deformable i.e. able to extend (stretch) in the radial direction. Stefan blowing is included. The Buongiorno dilute nanofluid model is adopted wherein Brownian motion and thermophoresis are the dominant nanoscale effects. The primitive conservation equations for mass, radial, tangential and axial momentum, heat (energy), nanoparticle concentration and micro-organism density function are formulated in a cylindrical polar coordinate system with appropriate wall and free stream boundary conditions. A mass convective condition is also incorporated at the disk surface. Forced convection is considered i.e. buoyancy forces are neglected. This highly nonlinear, strongly coupled system of unsteady partial differential equations is normalized with the classical Von Karman and other transformations to render the boundary value problem (BVP) into an ordinary differential system which is solved with the efficient Adomian decomposition method (ADM). Validation with earlier Runge-Kutta shooting computations in the literature is also conducted. Extensive computations are presented (with the aid of MATLAB symbolic software) for radial and circumferential velocity components, temperature, nanoparticle concentration, micro-organism density number and gradients of these functions at the disk surface (radial local skin friction, local circumferential skin friction, Local Nusselt number, Local Sherwood number, motile microorganism mass transfer rate). Main Findings- Increasing radial stretching parameter decreases radial velocity and radial skin friction, reduces azimuthal velocity and skin friction, decreases local Nusselt number and motile micro-organism mass wall flux whereas it increases nano-particle local Sherwood number. Disk deceleration accelerates the radial flow, damps the azimuthal flow, decreases temperatures and thermal boundary layer thickness, depletes the nano-particle concentration magnitudes (and associated nano-particle species boundary layer thickness) and furthermore decreases the micro-organism density number and gyrotactic micro-organism species boundary layer thickness. Increasing Stefan blowing accelerates the radial flow and azimuthal (circumferential flow), elevates temperatures of the nanofluid, boosts nano-particle concentration (volume fraction) and gyrotactic micro-organism density number magnitudes whereas suction generates the reverse effects. Increasing suction effect reduces radial skin friction and azimuthal skin friction, local Nusselt number, and motile micro-organism wall mass flux whereas it enhances the nano-particle species local Sherwood number. Conclusions - Important transport characteristics are identified of relevance to real bioreactor nanotechnological systems not discussed in previous works. ADM is shown to achieve very rapid convergence and highly accurate solutions and shows excellent promise in simulating swirling multi-physical nano-bioconvection fluid dynamics problems. Furthermore, it provides an excellent complement to more general commercial computational fluid dynamics simulations.

Keywords: bio-nanofluids, rotating disk bioreactors, Von Karman swirling flow, numerical solutions

Procedia PDF Downloads 156

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

Procedia PDF Downloads 88