Analysis of Post-Operative Pain Following Single Sitting Root Canal Treatment.

Background: The objective of root canal therapy is the complete cleansing and sealing of the entire root canal system, encompassing all of its elements. This current study was undertaken to evaluate the occurrence of postoperative pain in the patients during single-session RCT. Materials and Methods: A total of 70 maxillary central incisor teeth from 55 patients, representing both genders, were chosen for a one-session root canal procedure. Postoperative discomfort was measured using the Visual Analog Scale (VAS) at the following time intervals: 6 hours, 12 hours, 24 hours, and 48 hours following the treatment. Results: Among the 55 patients, there were 35 males and 20 females. The average VAS scores at various time points were as follows: 6 hours (7.4), 12 hours (5.2), 24 hours (3.4), and 48 hours (2.5). These differences were found to be statistically significant (P < 0.05). Conclusion: The authors observed a significant reduction in postoperative pain following a one-session RCT.

A Quality by Design Approach for Developing SNEDDS Loaded with Vemurafenib for Enhanced Oral Bioavailability.

Vemurafenib (VMF) is a practically insoluble (< 0.1 µg/mL) and least bioavailable (1%) drug. To enhance its oral bioavailability and solubility, we formulated a reliable self-nano emulsifying drug delivery system (SNEDDS). A Quality by Design (QbD) approach was used to optimize the ratio of Capryol 90, Tween 80, and Transcutol HP. VMF-loaded SNEDDS was characterized for its size, polydispersity index (PDI), zeta potential, drug content, and transmittance. The in vitro release profile of the drug loaded in SNEDDS was compared to the free drug in two media, pH 6.8 and 1.2, and the data obtained were analyzed with different mathematical models. A reverse-phase ultra-pressure liquid chromatography (UPLC) technique with high sensitivity and selectivity was developed and validated for the quantification of VMF in analytical and bioanalytical samples. Dissolution efficiency for SNEDDS was estimated using different models, which proved that the developed novel SNEDDS formulation had a better in vitro dissolution profile than the free drug. A 2.13-fold enhanced oral bioavailability of VMF-loaded SNEDDS compared to the free drug demonstrates the superiority of the developed formulation. This work thus presents an overview of VMF-loaded SNEDDS as a promising alternative to improve the oral bioavailability of the drug.

Three-dimensional eco-friendly bacterial nanocellulose (BNC) scaffold for regenerative dentistry: Characterization, cytocompatibility and differentiation potential.

OBJECTIVE: Regenerative dentistry (RD) is an innovative strategy for treating necrotic teeth and regenerating damaged dental tissue. Biocompatible materials are pivotal for the advancement of RD, and the rising interest in environmental sustainability drives exploration of sustainable materials for dentistry. Bacterial nanocellulose (BNC) has emerged as a promising eco-friendly option and this study aims to assess BNC's suitability as scaffolds for regenerative dentistry applications. METHODS: Different in vitro methods have been utilized to characterize the properties of BNC scaffolds in regenerative dentistry, such as scanning electron microscopy (SEM) to analyse surface property and porosity, as well as examining their absorption behaviour using phosphate-buffered saline and bovine serum. Dental pulp stem cell (DPSCs) attachment, viability, and proliferation were evaluated using SEM, live and dead, and tetrazolium reduction assays. The odontogenic potential of the scaffold was evaluated using Alizarin Red staining and qPCR (14 and 21 days). RESULTS: Scanning electron microscopy (SEM) images and ethanol displacement method demonstrated the porous architecture of the BNC scaffold with an average porosity of 70.02 ± 4.74% and 50.26 ± 1.43% respectively. The scaffold absorbed 2846.54 ± 258.95 of BSA and 1648.63 ± 50.37% PBS after immersion in solution for 1 h, following pseudo first and second order kinetics. The biocompatibility assay indicated that cell density increased with time and that the scaffold was appropriate for cell adhesion and migration. Moreover, the BNC led to significantly higher mineralization and odontogenic expression compared to the control (BNC in conditioned media). SIGNIFICANCE: BNC showed fast adsorption of bovine serum, allowed DPSC attachment, migration, and odontogenic differentiation. This suggests its suitability as a biocompatible scaffold for triggering in situ mineralized tissue regeneration for regenerative dental applications.

Recent Advancements in Nanocarrier-assisted Brain Delivery of Phytochemicals Against Neurological Diseases.

Despite ongoing advancements in research, the inability of therapeutics to cross the blood-brain barrier (BBB) makes the treatment of neurological disorders (NDs) a challenging task, offering only partial symptomatic relief. Various adverse effects associated with existing approaches are another significant barrier that prompts the usage of structurally diverse phytochemicals as preventive/therapeutic lead against NDs in preclinical and clinical settings. Despite numerous beneficial properties, phytochemicals suffer from poor pharmacokinetic profile which limits their pharmacological activity and necessitates the utility of nanotechnology for efficient drug delivery. Nanocarriers have been shown to be proficient carriers that can enhance drug delivery, bioavailability, biocompatibility, and stability of phytochemicals. We, thus, conducted a meticulous literature survey using several electronic databases to gather relevant studies in order to provide a comprehensive summary about the use of nanocarriers in delivering phytochemicals as a treatment approach for NDs. Additionally, the review highlights the mechanisms of drug transport of nanocarriers across the BBB and explores their potential future applications in this emerging field.

Enhanced apoptosis and mitochondrial cell death by paclitaxel-loaded TPP-TPGS1000-functionalized nanoemulsion.

Background: The present research was designed to develop a nanoemulsion (NE) of triphenylphosphine-D-α-tocopheryl-polyethylene glycol succinate (TPP-TPGS1000) and paclitaxel (PTX) to effectively deliver PTX to improve breast cancer therapy. Materials & methods: A quality-by-design approach was applied for optimization and in vitro and in vivo characterization were performed. Results: The TPP-TPGS1000-PTX-NE enhanced cellular uptake, mitochondrial membrane depolarization and G2M cell cycle arrest compared with free-PTX treatment. In addition, pharmacokinetics, biodistribution and in vivo live imaging studies in tumor-bearing mice showed that TPP-TPGS1000-PTX-NE had superior performance compared with free-PTX treatment. Histological and survival investigations ascertained the nontoxicity of the nanoformulation, suggesting new opportunities and potential to treat breast cancer. Conclusion: TPP-TPGS1000-PTX-NE improved the efficacy of breast cancer treatment by enhancing its effectiveness and decreasing drug toxicity.

HPLC method for simultaneous estimation of paclitaxel and baicalein: pharmaceutical and pharmacokinetic applications.

Aim: A novel HPLC method was developed and validated for the simultaneous estimation of paclitaxel (PTX) and baicalein (BAC). Materials & methods: The analytes were resolved in a C18 column using the aqueous solution of formic acid (0.10% v/v) and MeOH (30:70 v/v). Results: The developed method was found to be linear over the concentration ranges 0.039-10 µg/ml and 0.019-10 µg/ml for PTX and BAC, respectively. The lower limits of quantification obtained were 0.042 µg/ml and 0.361 µg/ml for PTX and BAC, respectively. Conclusion: The developed method was found to be precise and accurate as per the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines, for simultaneous estimation of PTX and BAC, having an application in formulation development and bioanalytical studies.

Gastroretentive Metformin Loaded Nanoparticles for the Effective Management of Type-2 Diabetes Mellitus.

INTRODUCTION: Metformin, an anti-diabetic drug, has low bioavailability and short biological half-life. Thus, bioavailability enhancement and prolonged release of the drug are highly desirable. In this regard, we aimed to developed gastroretentive nanoparticles made of jackfruit seed starch (JFSS) loaded with metformin. METHODS: Developed nanoparticles were optimized for various process variables and were further characterized. Nanoparticles exhibited good results with respect to particle size (244.3 to 612.4 nm), particle size distribution, shape and drug entrapment efficiency (75.8 to 89.2%) with sustained drug release for 24 h and a high buoyancy (89% for F7; formulation made of highest concentration of Jackfruit seed starch prepared at 1000 RPM stirring speed). RESULTS: The hypoglycemic potential of these nanoparticles was tested in nicotinamide streptozocin induced diabetic model, there was a significant reduction in blood glucose level (50% reduction from 4-8 h; p < 0.01) for prolonged period of time (up to 24 h) in comparison to diabetic control and plain metformin solution. CONCLUSION: The outcome of the study suggested that developed formulations are suitable for gastro- retentive delivery of Metformin in a controlled manner appropriate for a single administration per day.

Liposomes: An Emerging Approach for the Treatment of Cancer.

BACKGROUND: Conventional drug delivery agents for a life-threatening disease, i.e., cancer, lack specificity towards cancer cells, producing a greater degree of side effects in the normal cells with a poor therapeutic index. These toxic side effects often limit dose escalation of anti-cancer drugs, leading to incomplete tumor suppression/ cancer eradication, early disease relapse, and ultimately, the development of drug resistance. Accordingly, targeting the tumor vasculatures is essential for the treatment of cancer. OBJECTIVE: To search and describe a safer drug delivery carrier for the treatment of cancer with reduced systemic toxicities. METHOD: Data were collected from Medline, PubMed, Google Scholar, Science Direct using the following keywords: 'liposomes', 'nanocarriers', 'targeted drug delivery', 'ligands', 'liposome for anti-cancerous drugs', 'treatment for cancer' and 'receptor targeting.' RESULTS: Liposomes have provided a safe platform for the targeted delivery of encapsulated anti-cancer drugs for the treatment of cancer, which results in the reduction of the cytotoxic side effects of anti-cancer drugs on normal cells. CONCLUSION: Liposomal targeting is a better emerging approach as an advanced drug delivery carrier with targeting ligands for anti-cancer agents.

In Silico Molecular Interaction Studies of Chitosan Polymer with Aromatase Inhibitor: Leads to Letrozole Nanoparticles for the Treatment of Breast Cancer.

BACKGROUND: It takes a lot more studies to evaluate the molecular interaction of nanoparticles with the drug, their drug delivery potential and release kinetics. Thus, we have taken in silico and in vitro approaches into account for the evaluation of the drug delivery ability of the chitosan nanoparticles. OBJECTIVE: The present work was aimed to study the interaction of chitosan nanoparticles with appropriate aromatase inhibitors using in silico tools. Further, synthesis and characterization of chitosan nanoparticles having optimal binding energy and affinity between drug and polymer in terms of size, encapsulation efficiency were carried out. METHODS: In the current study, molecular docking was used to map the molecular interactions and estimation of binding energy involved between the nanoparticles and the drug molecules in silico. Letrozole is used as a model cytotoxic agent currently being used clinically; hence Letrozole loaded chitosan nanoparticles were formulated and characterized using photomicroscope, particle size analyzer, scanning electron microscope and fourier transform infra-red spectroscopy. RESULTS: Letrozole had the second-highest binding affinity within the core of chitosan with MolDock (-102.470) and Re-rank (-81.084) scores. Further, it was investigated that formulated nanoparticles were having superior drug loading capacity and high encapsulation efficiency. In vitro drug release study exhibited prolonged release of the drug from chitosan nanoparticles. CONCLUSION: Results obtained from the in silico and in vitro studies suggest that Letrozole loaded nanoparticles are ideal for breast cancer treatment.

In Silico Docking of Anti Cancerous Drugs with ß-Cyclodextrin polymer as a Prominent Approach to Improve the Bioavailability.

BACKGROUND: ß-Cyclodextrin, a cyclic oligosaccharides having 7 macrocyclic rings of glucose subunits usually linked together by α-1,4 glycosidic bond, bears characteristic chemical structure, with an exterior portion as hydrophilic to impart water solubility and interior cavity as hydrophobic, for hosting the hydrophobic molecules. OBJECTIVE: In the present work binding affinities and interactions between various anti-cancerous drugs and ß- cyclodextrin using molecular docking simulations was examined for the bioavailability enhancement of cytotoxic drugs through improved solubility for the treatment of breast cancer. METHODS: Molegro Virtual Docker, an integrated software was used for the prediction and estimation of interaction between ß-cyclodextrin and anti cancerous drugs. RESULTS: Out of tested anti cancerous drug, Olaparib having pyridopyridazione scaffold possess highest MolDock (-130.045) and Re-ranks score (-100.717), ensuring strong binding affinity. However, 5-Fluoro Uracil exhibited the lowest MolDock score (-61.0045), indicating weak or no binding affinity, while few drugs showed no H-bond interaction with the ß-cyclodextrin. CONCLUSION: The binding conformations of anti cancerous drugs obtained from the present study can be selected for the development of improved formulation having superior solubility which will lead to attain better pharmacological profile with negligible toxicity.

Polymeric Nanoparticles of Aromatase Inhibitors: A Comprehensive Review.

Being the second most frequent cancer, breast cancer is emerging worldwide with an alarming rate, specifically in post-menopausal women. Targeted drug delivery has been in the focus for the successful treatment of breast cancer by enhancing the drug delivery efficiency and reducing the systemic toxicity of drugs. Also, it eliminates the drawbacks associated with conventional chemotherapy, including neuropathy, memory loss, cardiotoxicity and low RBCs count. This review elaborates the polymeric nanoparticles based formulation approaches for selective and sustained delivery for effective cure of breast cancer. However, breast cancer, a life-threatening disease, is mostly caused because of estrogen, thus aromatase inhibitors and estrogen synthesis inhibitors could prevent chances of breast cancer. The disease is associated with drug resistance and some side effects, which could be easily eliminated by using novel therapeutic approaches. Aromatase inhibitors, when entrapped in nanoparticles, have shown sustained drug release, advocating themselves to be beneficial for the treatment of breast cancer.

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer.

AIM: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for site-specific delivery. BACKGROUND: Liver cancer is the third leading cause of death in the world and the fifth most often diagnosed cancer. It is a major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target-specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of the drug in normal tissues. OBJECTIVE: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5- FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for effective treatment of liver cancer. MATERIALS AND METHODS: 5-FU loaded JFSSNPs were prepared and optimized formulations having higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. The potential of NPs was studied using in vitro cytotoxicity assay, in vivo kinetic studies, and bio-distribution studies. RESULT AND DISCUSSION: 5-Fluorouracil loaded NPs had a particle size between 336 to 802 nm with drug entrapment efficiency between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of the drug in amorphous form. DSC study suggests there was no physical interaction between 5-FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assisted in the selective accumulation of 5-FU in the liver (vs. other organs spleen, kidney, lungs, and heart) compared to unconjugated one and plain drug. CONCLUSION: In vivo, bio-distribution, and plasma profile studies resulted in a significantly higher concentration of 5-Fluorouracil liver, suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

Repaglinide and Metformin-Loaded Amberlite Resin-Based Floating Microspheres for the Effective Management of Type 2 Diabetes.

BACKGROUND: Low bioavailability of anti-diabetic drugs results in the partial absorption of the drug as they are mainly absorbed from the stomach and the lower part of the GIT. Drug bioavailability of anti-diabetic drugs can be significantly increased by prolonging gastric retention time through gastro-retentive dosage form such as floating microspheres. OBJECTIVE: The study was aimed to develop and characterize resin based floating microspheres of Repaglinide and Metformin for superior and prolonged maintenance of normoglycaemia in type-2 diabetes mellitus. METHODS: Repaglinide and metformin were complexed with amberlite resin; later resin complexed drug was encapsulated in Ethylcellulose floating microspheres. Floating microspheres were characterized for morphology, particle size, IR spectroscopy, DSC, in vitro release and buoyancy studies. Further, floating microspheres were tested for in vivo blood glucose reduction potential in Streptozocin- induced diabetic mice. RESULTS: Floating microspheres had a spherical shape and slightly rough surface with the entrapment efficiency in a range of 49-78% for metformin and 52-73% for repaglinide. DSC studies revealed that no chemical interaction took place between polymer and drugs. Floating microspheres showed good buoyancy behavior (P<0.05) and prolonged drug release as compared to plain drug (P<0.05). The blood glucose lowering effect of floating microspheres on Streptozocin induced diabetic rats was significantly greater (P<0.05) and prolonged (˃12h) and normoglycaemia was maintained for 6hr. CONCLUSION: Floating microspheres containing drug resin complex were able to prolong drug release in an efficient way for a sustained period of time; as a result, profound therapeutic response was obtained.

Aromatase Inhibitors for the Treatment of Breast Cancer: A Journey from the Scratch.

BACKGROUND: Estrogens are essential for the growth of breast cancer in the case of premenopausal as well as in postmenopausal women. However, most of the breast cancer incidences are reported in postmenopausal women and the concurrent risk surges with an increase in age. Since the enzyme aromatase catalyses essential steps in estrogen biosynthesis, Aromatase Inhibitors (AIs) are effective targeted therapy in patients with Estrogen Receptor positive (ER+) breast cancer. AIs are more effective than Selective Estrogen Receptor Modulators (SERMs) because they block both the genomic and nongenomic activities of ER. Till date, first, second and third-generation AIs have been approved by the FDA. The third-generation AIs, viz. Letrozole, Anastrozole, Exemestane, are currently used in the standard treatment for postmenopausal breast cancer. METHODS: Data were collected from Medline, PubMed, Google Scholar, Science Direct through searching of keywords: 'aromatase', 'aromatase inhibitors', 'breast cancer', 'steroidal aromatase inhibitors', 'non-steroidal inhibitors' and 'generations of aromatase inhibitors'. RESULTS: In the current scenario of breast cancer chemotherapy, AIs are the most widely used agents which reveal optimum efficacy along with the least side effects. Keeping in view the prominence of AIs in breast cancer therapy, this review covered the detailed description of aromatase including its role in the biosynthesis of estrogen, biochemistry, gene expression, 3D-structure, and information of reported AIs along with their role in breast cancer treatment. CONCLUSION: AIs are the mainstream solution of the ER+ breast cancer treatment regimen with the continuous improvement of human understanding of the importance of a healthy life of women suffering from breast cancer.

Synchronized Electromechanical Shock Wave-Induced Bacterial Transformation.

We report a simple device that generates synchronized mechanical and electrical pressure waves for carrying out bacterial transformation. The mechanical pressure waves are produced by igniting a confined nanoenergetic composite material that provides ultrahigh pressure. Further, this device has an arrangement through which a synchronized electric field (of a time-varying nature) is initiated at a delay of ≈85 µs at the full width half-maxima point of the pressure pulse. The pressure waves so generated are incident to a thin aluminum-polydimethylsiloxane membrane that partitions the ignition chamber from the column of the mixture containing bacterial cells (Escherichia coli BL21) and 4 kb transforming DNA. A combination of mechanical and electrical pressure pulse created through the above arrangement ensures that the transforming DNA transports across the cell membrane into the cell, leading to a transformation event. This unique device has been successfully operated for efficient gene (∼4 kb) transfer into cells. The transformation efficacy of this device is found comparable to the other standard methods and protocols for carrying out the transformation.

Impact of surface roughness on Dielectrophoretically assisted concentration of microorganisms over PCB based platforms.

This article presents a PCB based microfluidic platform for performing a dielectrophoretic capture of live microorganisms over inter-digitated electrodes buried under layers of different surface roughness values. Although dielectrophoresis has been extensively studied earlier over silicon and polymer surfaces with printed electrodes the issue of surface roughness particularly in case of buried electrodes has been seldom investigated. We have addressed this issue through a layer of spin coated PDMS (of various surface roughness) that is used to cover the printed electrodes over a printed circuit board. The roughness in the PDMS layer is generally defined by the roughness of the FR4 base which houses the printed electrodes as well as other structures. Possibilities arising out of COMSOL simulations have been well validated experimentally in this work.