Novel vesicular bilosomal delivery systems for dermal/transdermal applications.

The application of therapeutically active molecules through the dermal/transdermal route into the skin has evolved as an attractive formulation strategy in comparison to oral delivery systems for the treatment of various disease conditions. However, the delivery of drugs across the skin is limited due to poor permeability. Dermal/transdermal delivery is associated with ease of accessibility, enhanced safety, better patient compliance, and reduced variability in plasma drug concentrations. It has the ability to bypass the first-pass metabolism, which ultimately results in steady and sustained drug levels in the systemic circulation. Vesicular drug delivery systems, including bilosomes, have gained significant interest due to their colloidal nature, improved drug solubility, absorption, and bioavailability with prolonged circulation time for a large number of new drug molecules. Bilosomes are novel lipid vesicular nanocarriers comprising bile salts, such as deoxycholic acid, sodium cholate, deoxycholate, taurocholate, glycocholate or sorbitan tristearate. These bilosomes are associated with high flexibility, deformability, and elasticity attributed to their bile acid component. These carriers are advantageous in terms of improved skin permeation, increased dermal and epidermal drug concentration, and enhanced local action with reduced systemic absorption of the drug, resulting in reduced side effects. The present article provides a comprehensive overview of the biopharmaceutical aspects of dermal/transdermal bilosome delivery systems, their composition, formulation techniques, characterization methods, and applications.

Colorectal cancer management: strategies in drug delivery.

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer leading to death worldwide following breast and lung cancer with the incidence rate of 10%. The treatment comprises surgery, radiation, and ablation therapy depending upon the stage of cancer. AREAS COVERED: The review focuses on various drug delivery strategies explored to circumvent the major constraints associated with the conventional drug delivery systems-poor bioavailability, intra- and inter individual variability, exposure of normal cells to antineoplastic agents, and presence of efflux pump. All these attributes impact the effective delivery of chemotherapeutic agents at the tumor site. The various target specific drug delivery systems developed for colorectal cancer include pH-dependent, microbiologically triggered, time-dependent, magnetically driven, pressure-dependent, prodrug/polysaccharide-based, osmotic and ligand-mediated systems. This review enumerates novel target specific approaches developed and investigated for potential utility in CRC therapeutics. EXPERT OPINION: The limitations of conventional delivery systems can be overcome by the development of colon-specific targeted drug delivery systems that overcome the obstacles of nonspecific biodistribution, drug resistance, and unwanted adverse effects of conventional drug delivery systems. In addition, nanotechnology approaches help to increase drug solubility, bioavailability, reduce side effects, and provide superior drug response in CRC.

Nanoparticles-Attractive Carriers of Antimicrobial Essential Oils.

Microbial pathogens are the most prevalent cause of chronic infections and fatalities around the world. Antimicrobial agents including antibiotics have been frequently utilized in the treatment of infections due to their exceptional outcomes. However, their widespread use has resulted in the emergence of multidrug-resistant strains of bacteria, fungi, viruses, and parasites. Furthermore, due to inherent resistance to antimicrobial drugs and the host defence system, the advent of new infectious diseases, chronic infections, and the occurrence of biofilms pose a tougher challenge to the current treatment line. Essential oils (EOs) and their biologically and structurally diverse constituents provide a distinctive, inexhaustible, and novel source of antibacterial, antiviral, antifungal, and antiparasitic agents. However, due to their volatile nature, chemical susceptibility, and poor solubility, their development as antimicrobials is limited. Nanoparticles composed of biodegradable polymeric and inorganic materials have been studied extensively to overcome these limitations. Nanoparticles are being investigated as nanocarriers for antimicrobial delivery, antimicrobial coatings for food products, implantable devices, and medicinal materials in dressings and packaging materials due to their intrinsic capacity to overcome microbial resistance. Essential oil-loaded nanoparticles may offer the potential benefits of synergism in antimicrobial activity, high loading capacity, increased solubility, decreased volatility, chemical stability, and enhancement of the bioavailability and shelf life of EOs and their constituents. This review focuses on the potentiation of the antimicrobial activity of essential oils and their constituents in nanoparticulate delivery systems for a wide range of applications, such as food preservation, packaging, and alternative treatments for infectious diseases.

Synthetic Strategies of Pyrimidine-Based Scaffolds as Aurora Kinase and Polo-like Kinase Inhibitors.

The past few decades have witnessed significant progress in anticancer drug discovery. Small molecules containing heterocyclic moieties have attracted considerable interest for designing new antitumor agents. Of these, the pyrimidine ring system is found in multitude of drug structures, and being the building unit of DNA and RNA makes it an attractive scaffold for the design and development of anticancer drugs. Currently, 22 pyrimidine-containing entities are approved for clinical use as anticancer drugs by the FDA. An exhaustive literature search indicates several publications and more than 59 patents from the year 2009 onwards on pyrimidine derivatives exhibiting potent antiproliferative activity. These pyrimidine derivatives exert their activity via diverse mechanisms, one of them being inhibition of protein kinases. Aurora kinase (AURK) and polo-like kinase (PLK) are protein kinases involved in the regulation of the cell cycle. Within the numerous pyrimidine-based small molecules developed as anticancer agents, this review focuses on the pyrimidine fused heterocyclic compounds modulating the AURK and PLK proteins in different phases of clinical trials as anticancer agents. This article aims to provide a comprehensive overview of synthetic strategies for the preparation of pyrimidine derivatives and their associated biological activity on AURK/PLK. It will also present an overview of the synthesis of the heterocyclic-2-aminopyrimidine, 4-aminopyrimidine and 2,4-diaminopyrimidine scaffolds, and one of the pharmacophores in AURK/PLK inhibitors is described systematically.