DEVELOPMENT OF BINARY AND TERNARY COMPLEX OF CEFUROXIME AXETIL WITH CYCLODEXTRIN FOR IMPROVING PHARMACEUTICAL CHARACTERISTICS

Objective: The current research objective is systematic development and characterization of binary and ternary inclusion complexes of cefuroxime axetil with β-cyclodextrin to improve its pharmaceutical characteristics by using the kneading method. Methods: Phase solubility study was carried out using Higuchi and Connors method. Based on its result, binary complexes of cefuroxime axetil with different ratio of β-cyclodextrin were developed and characterized using differential scanning calorimeter (DSC), fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffractometry (XRD). Then, binary complexes were analyzed for in vitro dissolution testing. The ternary complexes were developed using different ratio of PVP K-30 as a ternary component and evaluated for in vitro dissolution testing and in vitro taste masking. Results: Binary complex of cefuroxime axetil with β-cyclodextrin (1:1) showed better drug release than pure drug. During the development of the ternary complex, β-cyclodextrin (1:1) and 1% w/v PVP K-30 as a ternary agent resulted in an optimized ternary complex. The DSC, FT-IR and XRD studies clearly revealed the formation of binary and ternary complexes. The ternary complex showed better drug release of>85% within 30 min. in comparison to binary complex. The in vitro taste-masking study revealed the taste masking efficiency of the ternary complex of cefuroxime with β-cyclodextrin. Conclusion: The developed binary and ternary complex of cefuroxime axetil based on β-cyclodextrin with PVP K-30 showed improved in vitro dissolution rate and taste masking in comparison to pure drug. The drug release was better in ternary complexes. The present research work successfully shows the utility of binary and ternary complexes for improving pharmaceutical characteristics of cefuroxime axetil

Central Composite Designed Formulation, Characterization and In-Vitro Cytotoxic effect of Erlotinib Loaded Chitosan Nanoparticulate System

© 2019 Elsevier B.V. The most common cause of deaths due to cancers nowadays is lung cancer. The objective of this study was to prepare erlotinib loaded chitosan nanoparticles for their anticancer potential. To study the effect of formulation variables on prepared nanoparticles using central composite design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using probe sonication technique. It was found that batch NP-7 has a maximum loading capacity and entrapment efficiency with a particle size (138.5 nm) which is ideal for targeting solid tumors. Analysis of variance was applied to the particle size, entrapment efficiency and percent cumulative drug release to study the fitting and the significance of the model. The batch NP-7 showed 91.57% and 39.78% drug release after 24 h in 0.1 N hydrochloric acid and Phosphate Buffer (PB) pH 6.8, respectively. The IC50 value of NP-7 evaluated on A549 Lung cancer cells was found to be 6.36 μM. The XRD of NP-7 displayed the existence of erlotinib in the amorphous pattern. The optimized batch released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using sonication technique with suitable particle size, entrapment efficiency and drug release. The formulated nanoparticles can be utilized for the treatment of lung cancer

Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update

Respiratory disorders, especially non-communicable, chronic inflammatory diseases, are amongst the leading causes of mortality and morbidity worldwide. Respiratory diseases involve multiple pulmonary components, including airways and lungs that lead to their abnormal physiological functioning. Several signaling pathways have been reported to play an important role in the pathophysiology of respiratory diseases. These pathways, in addition, become the compounding factors contributing to the clinical outcomes in respiratory diseases. A range of signaling components such as Notch, Hedgehog, Wingless/Wnt, bone morphogenetic proteins, epidermal growth factor and fibroblast growth factor is primarily employed by these pathways in the eventual cascade of events. The different aberrations in such cell-signaling processes trigger the onset of respiratory diseases making the conventional therapeutic modalities ineffective. These challenges have prompted us to explore novel and effective approaches for the prevention and/or treatment of respiratory diseases. In this review, we have attempted to deliberate on the current literature describing the role of major cell signaling pathways in the pathogenesis of pulmonary diseases and discuss promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing pulmonary vascular pathology in such patients

Analytical Estimation of Data-Motivated Time-Dependent Disease Transmission Rate: An Application to Ebola and Selected Public Health Problems

Obtaining reasonable estimates for transmission rates from observed data is a challenge when using mathematical models to study the dynamics of ?infectious? diseases, like Ebola. Most models assume the transmission rate of a contagion either does not vary over time or change in a fixed pre-determined adhoc ways. However, these rates do vary during an outbreak due to multitude of factors such as environmental conditions, social behaviors, and public-health interventions deployed to control the disease, which are in-part guided by changing size of an outbreak. We derive analytical estimates of time-dependent transmission rate for an epidemic in terms of either incidence or prevalence using a standard mathematical SIR-type epidemic model. We illustrate applicability of our method by applying data on various public health problems, including infectious diseases (Ebola, SARS, and Leishmaniasis) and social issues (obesity and alcohol drinking) to compute transmission rates over time. We show that time-dependent transmission rate estimates can have a large variation, depending on the type of available data and other epidemiological parameters. Time-dependent estimation of transmission rates captures the dynamics of the problem better and can be utilized to understand disease progression more accurately

Potential Role of Curcumin and Its Nanoformulations to Treat Various Types of Cancers

Cancer is a major burden of disease globally. Each year, tens of millions of people are diagnosed with cancer worldwide, and more than half of the patients eventually die from it. Significant advances have been noticed in cancer treatment, but the mortality and incidence rates of cancers are still high. Thus, there is a growing research interest in developing more effective and less toxic cancer treatment approaches. Curcumin (CUR), the major active component of turmeric (Curcuma longa L.), has gained great research interest as an antioxidant, anticancer, and anti-inflammatory agent. This natural compound shows its anticancer effect through several pathways including interfering with multiple cellular mechanisms and inhibiting/inducing the generation of multiple cytokines, enzymes, or growth factors including I kappa B kinase beta (I kappa K beta), tumor necrosis factor-alpha (TNF-alpha), signal transducer, and activator of transcription 3 (STAT3), cyclooxygenase II (COX-2), protein kinase D1 (PKD1), nuclear factor-kappa B (NF-kappa B), epidermal growth factor, and mitogen-activated protein kinase (MAPK). Interestingly, the anticancer activity of CUR has been limited primarily due to its poor water solubility, which can lead to low chemical stability, low oral bioavailability, and low cellular uptake. Delivering drugs at a controlled rate, slow delivery, and targeted delivery are other very attractive methods and have been pursued vigorously. Multiple CUR nanoformulations have also been developed so far to ameliorate solubility and bioavailability of CUR and to provide protection to CUR against hydrolysis inactivation. In this review, we have summarized the anticancer activity of CUR against several cancers, for example, gastrointestinal, head and neck, brain, pancreatic, colorectal, breast, and prostate cancers. In addition, we have also focused on the findings obtained from multiple experimental and clinical studies regarding the anticancer effect of CUR in animal models, human subjects, and cancer cell lines

Emerging Complexity and the Need for Advanced Drug Delivery in Targeting Candida Species

BACKGROUND: Candida species are the important etiologic agents for candidiasis, the most prevalent cause of opportunistic fungal infections. Candida invasion results in mucosal to systemic infections through immune dysfunction and helps in further invasion and proliferation at several sites in the host. The host defence system utilizes a wide array of the cells, proteins and chemical signals that are distributed in blood and tissues which further constitute the innate and adaptive immune system. The lack of antifungal agents and their limited therapeutic effects have led to high mortality and morbidity related to such infections. METHODS: The necessary information collated on this review has been gathered from various literature published from 1995 to 2019. RESULTS: This article sheds light on novel drug delivery approaches to target the immunological axis for several Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. rugose, C. hemulonii, etc.). CONCLUSION: It is clear that the novel drug delivery approaches include vaccines, adoptive transfer of primed immune cells, recombinant cytokines, therapeutic antibodies, and nanoparticles, which have immunomodulatory effects. Such advancements in targeting various underpinning mechanisms using the concept of novel drug delivery will provide a new dimension to the fungal infection clinic particularly due to Candida species with improved patient compliance and lesser side effects. This advancement in knowledge can also be extended to target various other similar microbial species and infections.</p

Systematic Analysis of Mycobacterial Acylation Reveals First Example of Acylation-mediated Regulation of Enzyme Activity of a Bacterial Phosphatase

Protein lysine acetylation is known to regulate multiple aspects of bacterial metabolism. However, its presence in mycobacterial signal transduction and virulence-associated proteins has not been studied. In this study, analysis of mycobacterial proteins from different cellular fractions indicated dynamic and widespread occurrence of lysine acetylation. Mycobacterium tuberculosis proteins regulating diverse physiological processes were then selected and expressed in the surrogate host Mycobacterium smegmatis. The purified proteins were analyzed for the presence of lysine acetylation, leading to the identification of 24 acetylated proteins. In addition, novel lysine succinylation and propionylation events were found to co-occur with acetylation on several proteins. Protein-tyrosine phosphatase B (PtpB), a secretory phosphatase that regulates phosphorylation of host proteins and plays a critical role in Mycobacterium infection, is modified by acetylation and succinylation at Lys-224. This residue is situated in a lid region that covers the enzyme's active site. Consequently, acetylation and succinylation negatively regulate the activity of PtpB