PLGA NANOPARTICLES LOADED MUCOADHESIVE AND THERMOSENSITIVE HYDROGEL AS A POTENTIAL PLATFORM FOR THE TREATMENT OF ORAL MUCOSITIS

Objective: The objective of this study was to design an effective topical treatment for oral mucositis.Methods: Poly-(DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs) and Poloxamer407 (PLX)/Hydroxy propyl methyl cellulose (HPMC) hydrogel matrix (HG) were used as combined carriers for benzydamine HCL (BNZ). BNZ loaded PLGA nanoparticles were assessed for their particle size, PDI, zeta potential and entrapment efficiency. Scanning electron microscopy, thermosensitivity study, mucoadhesion study, in vitro release and in vivo investigation were used to characterize the combined BZN loaded PLGA NPs HG.Results: Negatively charged NPs with an average diameter of 139±4.92 nm were incorporated into PLX/HPMC HG bases. The gelation temperature of BZN-PLGA-NPs-HGs ranged between 31°C and 36.5°C. When diluted with saliva simulated fluid, BZN-PLGA-NPs-HGs preserved their gelation properties. Mucoadhesion was found lower for formulations prepared with PLX without HPMC. An increase in the concentrations of PLX from 10 to 30% resulted in an increase in adhesion. Both PLGA-NPs and PLGA-NPs-HG provided a biphasic drug release profile while BZN-HG provided monophasic zero order release pattern. The in vivo study showed that animal groups treated with BZN-HG and BZN-PLGA-NPs-HG showed a significantly higher reduction percentage in ulcer surface area compared to those treated with BZN-PLGA-NPs. BZN-PLGA-NPs-HG group needed 10 d of treatment to complete healing versus 16 d, 14 d and 12 d for the complete healing of groups with no treatment, treated with BZN-PLGA-NPs and treated with BZN-HG, respectively.Conclusion: BZN-PLGA-NPs-HG could represent a promising mean for the effective treatment of oral mucositis induced by cancer therapy

FORMULATION AND EVALUATION OF FLURBIPROFEN SUSTAINED RELEASE MATRIX TABLETS USING AN ALTERNATIVE TECHNIQUE AS POTENTIAL ECONOMIC APPROACH

Objective: Development of sustained released tablets of flurbiprofen (FP) using an alternative technique to the traditional method of wet granulation process aiming to lower labor cost of the granulation process and formulating tablets with better characteristics. Methods: Eight matrix tablets formulae of FP were prepared by the alternative technique. The various characteristics of FP prepared tablets were investigated and comparatively evaluated by FP tablets prepared by the traditional method. The release data was analyzed according to various kinetic equations. The ulcerogenic effects of some FP tablets formulae were evaluated. Results: FP tablets prepared by the alternative technique displayed the best physical characteristics. All FP prepared tablets displayed good sustained-release patterns. FP tablets prepared by the traditional method showed a progress decrease in drug dissolution by increasing matrix concentration and hence, more matrix agent or multiple granulations was needed which makes granulation process to be difficult and cost. While, FP tablets prepared by the alternative technique displayed dissolution profiles with minimal differences in-between reflecting the low labor cost of granulation process where good sustained patterns could be obtained by a minor of the matrix agent. Histologically, the ulcerogenic effects of FP on the rats were highly reduced by FP tablets prepared by the alternative technique rather than others. The release kinetics of different prepared FP tablets displayed a coupled release pattern between diffusion and dissolution. Conclusion: This work proved the potential of the alternative technique as an effective economic approach for formulating FP sustained released tablets with better characteristics and low labor cost

Hormonal and inflammatory modulatory effects of hesperidin in hyperthyroidism-modeled rats

The goal of the current study was to investigate the hormonal modulatory efficiency of hesperidin, through its regulatory potential of immunological, inflammatory, and/or antioxidant changes in on hyperthyroidism modeled adult female albino rats. Both normal and hyperthyroidism modeled rats (140-160g) were randomly divided into four groups (10 animals each) as follows: 1) healthy animals were daily ingested with saline for six weeks, and served as control group, 2) healthy animals were intraperitoneally injected with hesperidin (50 mg/kg/day) for a similar period, 3) hyperthyroidism-modeled animals without any treatment acted as positive control, and 4) hyperthyroidism-modeled animals were treated intraperitoneally with hesperidin for a similar period. The findings showed that hesperidin significantly modulated hyperthyroidism deteriorations, this was evidenced by a remarkable decline in serum T4, FT4, T3, FT3, TNF-α, IL1β-, IL4-, IL-6, and IL-10 levels, with a minor increase in TSH and significant raise in CD4+ level. Similarly, valuable improvement was observed in the oxidative status; serum SOD, GPx, CAT, and GSH levels were dramatically enhanced, associated with remarkable drop in MDA and NO levels. Also, hesperidin demonstrated nephro-hepatoprotective and anti-atherogenic potential, this was achieved from the notable reduction in ALAT and ASAT activities as well as urea, creatinine, cholesterol, and triglyceride close to the corresponding values of healthy group. These findings were supported by histological and immunohistochemical ones that showed a notable decrease in the expression of the calcitonin antibody. In conclusion, hesperidin possesses anti-hyperthyroidism, immunoinflammatory regulatory, and antioxidant activities that evidenced from the improvement of physio-architecture of the thyroid gland, reduction of inflammation and restoration of the impaired oxidative stress. This effect might be mechanized through immunological, inflammatory, apoptotic, and/or antioxidant modulatory pathways

Prospective monitoring improves outcomes of primary total hip replacement: a cohort study

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Novel gold nanoparticles coated with somatostatin as a potential delivery system for targeting somatostatin receptors

Targeting of G-protein coupled receptors (GPCRs) like somatostatin-14 (SST-14) could have a potential interest in delivery of anti-cancer agents to tumor cells. Attachment of SST to different nano-carriers e.g., polymeric nanoparticles is limited due to the difficulty of interaction between SST itself and those nano-carriers. Furthermore, the instability problems associated with the final formulation. Attaching of SST to gold nanoparticles (AuNPs) using the positive and negative charge of SST and citrate-AuNPs could be considered a new technique to get stable non-aggregated AuNPs coated with SST. Different analyses techniques have been performed to proof the principle of coating between AuNPs and SST. Furthermore, cellular uptake study on HCC-1809 cell lines has been investigated to show the ability of AuNPs coated SST to enter the cells via SST receptors. Dynamic light scattering (DLS) indicated a successful coating of SST on the MUA-AuNPs surface. Furthermore, all the performed analysis including DLS, SDS-PAGE and UV-VIS absorption spectra indicated a successful coating of AuNPs with SST. Cellular uptake study on HCC-1806 cell lines showed that the number of AuNPs-SST per cell is significantly higher compared to citrate-AuNPs when quantified using inductively coupled plasma spectroscopy. Moreover, the binding of AuNPs-SST to cells can be suppressed by addition of antagonist, indicating that the binding of AuNPs-SST to cells is due to receptor-specific binding. In conclusion, AuNPs could be attached to SST via adsorption to get stable AuNPs coated SST. This new formulation has a potential to target SST receptors localized in many normal and tumor cells

GROWTH FACTOR LOADED FUNCTIONALIZED GOLD NANOPARTICLES AS POTENTIAL TARGETED TREATMENT FOR ACUTE RENAL FAILURE

Objective: Gold nanoparticles (GNPs) have been synthesized and functionalized with chitosan alkanethiol polyethylene glycol as a renal targeting ligand (CS-PEG-AlkSH-GNPs) and finally loaded with insulin-like growth factor-I (IGF-I) for selectively and effectively treating acute renal failure.Methods: In this study, GNPs were prepared and characterized using transmission electron microscopy, photon correlation spectroscopy and inductively coupled plasma (ICP-OES). The surface of the GNPs was further decorated using synthesized CS-PEG-Alk-SH and IGF-I. IGF-I loaded CS-PEG-ALK-SH-GNP were characterized for their growth factor loading capacity, particle size, zeta potential and dispersion stability. In vitro release profile and bioactivity of IGF-I from IGF-I loaded CS-PEG-AlkSH-GNPs were assessed using cell culture technique. Biological distribution, pharmacokinetic investigation and toxicity study of IGF-I loaded CS-PEG-AlkSH-GNPs were carried out using experimental animals.Results: The size of GNPs was less than 50 nm with a surface charge of about-45 mV. Coating GNPs with CS-PEG-Alk-SH acquired the particles high in vitro stability in 5 M NaCl and bovine serum albumin (BSA). The assembly's bioactivity was tested on cell culture and the released IGF-I was found to maintain bioactivity equivalent to its released percentage. When tested on mice, IGF-I loaded CS-PEG-ALK-SH-GNP reached a concentration of 60% in 6 h time in the kidneys with an elimination half-life higher than that of the control GNPs indicating efficient renal residence and targeting processes. The system was proved nontoxic.Conclusion: CS-PEG-AlkSH-GNPs could represent an efficient tool for the targeted delivery of growth factors and other biomolecules to the kidneys.Â

Analytical Study of Fractional Epidemic Model via Natural Transform Homotopy Analysis Method

In this study, we present a new general solution to a rational epidemiological mathematical model via a recent intelligent method called the natural transform homotopy analysis method (NTHAM), which combines two methods: the natural transform method (NTM) and homotopy analysis method (HAM). To assess the precision and the reliability of the present method, we compared the obtained results with those of the Laplace homotopy perturbation method (LHPM) as well as the q-homotopy analysis Sumudu transform method (q-HASTM), which revealed that the NTHAM is more reliable. The Caputo fractional derivative is employed. It not only gives initial conditions with obvious natural interpretation but is also bounded, meaning that there is no derivative of a constant. The results show that the proposed technique is superior in terms of simplicity, quality, accuracy, and stability and demonstrate the effectiveness of the rational technique under consideration

Mucosal co-delivery of ketorolac and lidocaine using polymeric wafers for dental application

The current study aimed to investigate the effectiveness of a developed sodium alginate and polyvinylpyrrolidone K-25 (PVP K-25) polymeric wafer for the co-delivery of ketorolac and lidocaine to soft tissues for healing and pain control following gingivectomy. Nine ketorolac/lidocaine lyophilized wafers were formulated and assessed for their hydration capacity, mucoadhesion ability and in vitro release profile to select the optimum system for further clinical investigation. Wafer F6 containing 2:1 sodium alginate to PVP K-25 and 10% glycerol showed optimum properties and was selected for the clinical study. Twenty patients were included in the study and the ketorolac/lidocaine wafer was assessed versus a market product. Visual pain analog was evaluated daily for the first week and wound healing index was evaluated for one week, two weeks and one month following the procedure. The developed ketorolac/lidocaine polymeric wafer proved to be an effective method of reducing pain and discomfort together with enhancing wound healing following gingivectomy

An Efficient Fault Diagnosis Framework for Digital Twins Using Optimized Machine Learning Models in Smart Industrial Control Systems

Abstract In recent times, digital twins (DT) is becoming an emerging and key technology for smart industrial control systems and Industrial Internet of things (IIoT) applications. The DT presently supports a significant tool that can generate a huge dataset for fault prediction and diagnosis in a real-time scenario for critical industrial applications with the support of powerful artificial intelligence (AI). The physical assets of DT can produce system performance data that is close to reality, which delivers remarkable opportunities for machine fault diagnosis for effective measured fault conditions. Therefore, this study presents an intelligent and efficient AI-based fault diagnosis framework using new hybrid optimization and machine learning models for industrial DT systems, namely, the triplex pump model and transmission system. The proposed hybrid framework utilizes a combination of optimization techniques (OT) such as the flower pollination algorithm (FPA), particle swarm algorithm (PSO), Harris hawk optimization (HHO), Jaya algorithm (JA), gray wolf optimizer (GWO), and Salp swarm algorithm (SSA), and machine learning (ML) such as K-nearest neighbors (KNN), decision tree (CART), and random forest (RF). The proposed hybrid OT–ML framework is validated using two different simulated datasets which are generated from both the mechanized triplex pump and transmission system models, respectively. From the experimental results, the hybrid FPA–CART and FPA–RF models within the proposed framework give acceptable results in detecting the most relevant subset of features from the two employed datasets while maintaining fault detection accuracy rates exemplified by the original set of features with 96.8% and 85.7%, respectively. Therefore, the results achieve good and acceptable performance compared to the other existing models for fault diagnosis in real time based on critical IIoT fields