Integrating Nanotherapeutic Platforms to Image Guided Approaches for Management of Cancer

Cancer is a leading cause of mortality worldwide, accounting for 8.8 million deaths in 2015. The landscape of cancer therapeutics is rapidly advancing with development of new and sophisticated approaches to diagnostic testing. Treatment plan for early diagnosed patients include radiation therapy, tumor ablation, surgery, immunotherapy and chemotherapy. However the treatment can only be initiated when the cancer has been diagnosed thoroughly. Theranostics is a term that combines diagnostics with therapeutics. It embraces multiple techniques to arrive at comprehensive diagnosis, molecular images and an individualized treatment regimen. Recently, there is an effort to tangle the emerging approach with nanotechnologies, in an attempt to develop theranostic nanoplatforms and methodologies. Theranostic approach to management of cancer offers numerous advantages. They are designed to monitor cancer treatment in real time. A wide variety of theranostic nanoplatforms that are based on diverse nanostructures like magnetic nanoparticles, carbon nanotubes, gold nanomaterials, polymeric nanoparticles and silica nanoparticles showed great potential as cancer theranostics. Nano therapeutic platforms have been successful in integrating image guidance with targeted approach to treat cancer.

Potassium Channels as a Potential Target Spot for Drugs

Aberrant function or expression of potassium channels can be underlying in pathologies such as cardiac arrhythmia, diabetes mellitus, hypertension, preterm birth, and various types of cancer. The expression of potassium channels is altered in many types of diseases. Also, we have previously shown that natural polyphenols, such as resveratrol, and selective synthetic modulators of potassium channels, like pinacidil, can alter their function and lead to the desired outcome. Therefore, targeting potassium channels with substance, which has an influence on their function, is promising access to cancer, diabetes mellitus, preterm birth, or hypertension therapy. In this chapter, we could discuss strategies for targeting different types of potassium channels as potential targets for synthetic and natural molecules therapy.

Allosteric Modulators for GPCRs as a Therapeutic Alternative with High Potential in Drug Discovery

The superfamily of G protein-coupled receptors (GPCRs) consists of biological microprocessors that can activate multiple signaling pathways. Most GPCRs have an orthosteric pocket where the endogenous ligand(s) typically binds. Conversely, allosteric ligands bind to GPCRs at sites that are distinct from the orthosteric binding region and they modulate the response elicited by the endogenous ligand. Allosteric ligands can also switch the response of a GPCR after ligand binding to a unique signaling pathway, these ligands are termed biased allosteric modulators. Thus, the development of allosteric ligands opens new and multiple ways in which the signaling pathways of GPCRs can be manipulated for potential therapeutic benefit. Furthermore, the mechanisms by which allosteric ligands modulate the effects of endogenous ligands have provided new insights into the interactions between allosteric ligands and GPCRs. These new findings have a high potential to improve drug discovery and development and, therefore, creating the need for better screening methods for allosteric drugs to increase the chances of success in the development of allosteric modulators as lead clinical compounds.

Integrated Molecular Profiling as an Approach to Identify PI3K Inhibitor Resistance Mechanisms

The identification of drug resistance pathways and approaches to target these pathways remains a significant and important challenge in cancer biology. Here, we address this challenge in the context of ongoing efforts to advance phosphatidylinositol 3-kinase (PI3K) inhibitors for the treatment of PI3K-aberrant cancers. While PI3K inhibitors have had tremendous success in some diseases, such as breast cancer, early clinical trials in other malignancies, such as head and neck squamous cell carcinoma (HNSCC), have not had the same level of success. Since HNSCC and other cancers display relatively high PI3K pathway alteration rates (>45%), these underwhelming results suggest that additional or unexpected factors may contribute to the lower response rates. Here, we highlight some of the emerging functional genomic and sequencing approaches being used to identify predictive biomarkers of PI3K inhibitor response using both cancer cell lines and clinical trial specimens. Importantly, these approaches have uncovered both innate genetic and adaptive mechanisms driving PI3K inhibitor resistance. In this chapter, we describe recent technological advances that have revolutionized our understanding of PI3K inhibitor resistance pathways in HNSCC and highlight how these and other approaches lay the groundwork to make significant strides in our understanding of molecular pharmacology in the cancer field.

3D-Printed Modified-Release Tablets: A Review of the Recent Advances

The broad spectrum of applications of three-dimensional printing (3D printing, 3DP) has attracted the attention of researchers working in diverse fields. In pharmaceutics, the main idea behind 3D printing products is to design and develop delivery systems that are suited to an individual’s needs. In this way, the size, appearance, shape, and rate of delivery of a wide array of medicines could be easily adjusted. The aim of this chapter is to provide a compilation of the 3D printing techniques, used for the fabrication of oral drug delivery systems, and review the relevant scientific developments in particular those with modified-release characteristics.

Liposome-A Comprehensive Approach for Researchers

Bangham was first to develop these spherical-shaped nano-vesicles called liposomes in the early 1960s. Today, liposomes have emerged as crucial tools for bettering the delivery of drugs that majorly includes-antifungal drug, peptide hormones, enzymes, vaccines antimicrobial agents, drugs against cancer, and genetic materials. Following the different manufacturing practices and versatile properties liposomes can be categorized in various parameters of size, charge, poly-dispersity index, encapsulation efficiency, solubility properties, and lamellarity. Alteration in such parameters elevates the loading and bioavailability of a drug by giving more clear target specification, desired or controlled release. This bibliographic chapter provides a comprehensive overview of methods for the preparation of liposomes with other perspectives that majorly includes—physio-chemical characteristics, dosage regimen, advantages over other delivery systems, approved liposomal based drugs and other ongoing drugs in clinical trials. It will help researchers to breakthrough more structurally successful delivery vehicles depending upon their various physic-chemical properties.

Preparation and in vitro Characterisation of Solid Dispersion Floating Tablet by Effervescent Control Release Technique with Improved Floating Capabilities

In this research, an effort has been done for the development of effervescent controlled release floating tablet (ECRFT) from solid dispersions (SDs) of diclofenac sodium (DS) for upsurge the solubility and dissolution rate. ECRFT of DS was prepared by using SDs of DS and its SDs prepared with PEG as carrier using thermal method (simple fusion). SDs of DS was formulated in many ratios (1:1, 1:2, 1:3 and 1:4). Prepared SDs were optimised for its solubility, % drug content and % dissolution studies. Tablets were formulated by using optimised SDs products and all formulation was evaluated for various parameters. A clear rise in dissolution rate was detected with entirely SD, amid that the optimised SD (SD4) was considered for ECRFT. Among all the tablet formulations, its F3 formulation was better in all the terms of pre-compression and post-compression parameters. It had all the qualities of a good ECRFT, based on this F3 formulation was selected as the best formulation. Data of in vitro release were fitted in several kinetics models to explain release mechanism. The F3 formulation shows zero order release. From this study, we can conclude that ECRFT containing SDs of DS can be successfully used for achieving better therapeutic objective.

Fibril Formation by Glucagon in Solution and in Membrane Environments

Glucagon is a 29-amino acid peptide hormone secreted by pancreatic α-cells and interacts with specific receptors located in various organs. Glucagon tends to form gel-like fibril aggregates that are cytotoxic because they activate apoptotic signaling pathways. First, fibril formation by glucagon in acidic solution is discussed in light of morphological and structural changes during elapsed time. Second, we provide kinetic analyses using a two-step autocatalytic reaction mechanism; the first step is a homogeneous nuclear formation process, and the second step is an autocatalytic heterogeneous fibril elongation process. Third, the processes of fibril formation by glucagon in a membrane environment are discussed based on the structural changes in the fibrils. In the presence of bicelles in acidic solution, glucagon interacts with the bicelles and forms fibril intermediates on the bicelle surface and grows into elongated fibrils. Glucagon-dimyristoylphosphatidylcholine (DMPC) bilayers in neutral solution mimic the environment for fibril formation by glucagon under near-physiological condition. Under these conditions, glucagon forms fibril intermediates that grow into elongated fibrils inside the lipid bilayer. Many days after preparing the glucagon-DMPC bilayer sample, the fibrils form networks inside and outside the bilayer. Furthermore, fibril intermediates strongly interact with lipid bilayers to form small particles.