Current Drug Metabolism - Volume 16, Issue 4, 2015

Acne vulgaris, a multi-factorial disease, is one of the most common skin diseases, affecting an estimated 80% of Americans at some point during their lives. The gram-positive and anaerobic Propionibacterium acnes (P. acnes) bacterium has been implicated in acne inflammation and pathogenesis. Therapies for acne vulgaris using antibiotics generally lack bacterial specificity, promote the generation of antibiotic-resistant bacterial strains, and cause adverse effects. Immunotherapy against P. acnes or its antigens (sialidase and CAMP factor) has been demonstrated to be effective in mice, attenuating P. acnes-induced inflammation; thus, this method may be applied to develop a potential vaccine targeting P. acnes for acne vulgaris treatment. This review summarizes reports describing the role of P. acnes in the pathogenesis of acne and various immunotherapy-based approaches targeting P. acnes, suggesting the potential effectiveness of immunotherapy for acne vulgaris as well as P. acnes-associated diseases.

Nanoparticles can be effective drug delivery systems for treating bacterial and fungal infections in the skin. The nanoparticles used for drug therapy give many advantages over conventional formulations, such as increased solubility and storage stability, improved permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. In recent years, the concept of using nanoparticles to treat skin-microbiomerelated diseases has attracted increasing attention. This review article aimed to introduce recent progress using nanomedical strategies for drug delivery. Various modalities of nanocarriers can be used for antimicrobial therapy of disease, including liposomes, microemulsions, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and polymeric nanoparticles. This review systematically describes the structures and physicochemical properties of different nanocarriers, emphasizing antibacterial activity of nanoparticles for inhibiting infection. Nanoparticles for treating appendageal bacteria have gained attention in recent years, in particular, nanomedical approaches for managing acne. Issues related to the treatment of non-appendageal bacteria and fungi are also discussed. Finally, current obstacles to using nanocarriers for delivering medicines aimed at inhibiting infection and future developments are addressed.

The gut microbiota is a complex ecosystem that affects the development, nutritional status and immunological responses of the host. Prokaryotes and fungi in the community have the abilities to withstand the adverse conditions of high temperature, low oxygen etc. and to decompose complex organic molecules. The novel approaches of metagenomics and metaproteomics provide data that allow the detection of patterns of constancy or changes in time or under different conditions, such as different diets, disease condition and antibiotic therapy. These large-scale patterns can be correlated with certain health or disease conditions. From the organismic point of view, however, the species identity of the organisms and their interactions in the gut and how these interactions influence the prevention or development of disease are poorly known. The diversity and roles of fungi in animal feces appear to be better known than in human gut/feces. A combined compilation of the diverse methods applied towards prokaryotes and fungi in the gut/feces microbiome serves as a base for meeting the challenges of masses of large-scale datasets on the one hand and lack of substantial organismic understanding on the other. Starting from long-term monitoring and large-scale characterization of the composition of microbiome from systematic higher groups down to the genus level, microbial genomes and proteomes, particular key components with antimicrobial or immune functions can be selected and investigated in detail with respect to understanding of host-microbiota interaction, disease pathogenesis and developing diagnostic and therapeutic tools.

It is now very much clear that the microbiome plays an important part in human health. Microbiome is associated with several diseases and targeting the whole microbiome is certainly a challenge before the scientists. The “Human Microbiome Project” is continually exploring certain therapeutic targets inside microbiome landscape that could be utilized for the treatment of microbiome associated diseases. Additionally, associated research across the globe is going on and now some potential targets are available that might be beneficial for the designing and synthesis of novel drugs. In this review, we made an effort to discuss all the potential targets and corresponding possible drugs/treatments available for each of them. However, it is not possible to treat all microbiome associated diseases with a single drug/drug combination. Therefore, for different diseases, different treatments/drugs (whether xenobiotic or non-xenobiotic) could be used for better therapeutic efficacy.

The wide-reaching distributed angiosperm family Ranunculaceae has approximately 2200 species in around 60 genera. Chemical components of this family include several representative groups: benzylisoquinoline alkaloid (BIA), ranunculin, triterpenoid saponin and diterpene alkaloid, etc. Their extensive clinical utility has been validated by traditional uses of thousands of years and current evidence-based medicine studies. Drug metabolism and pharmacokinetic (DMPK) studies of plant-based natural products are an indispensable part of comprehensive medicinal plant exploration, which could facilitate conservation and sustainable utilization of Ranunculaceae pharmaceutical resources, as well as new chemical entity development with improved DMPK parameters. However, DMPK characteristics of Ranunculaceaederived medicinal compounds have not been summarized. Black cohosh (Cimicifuga) and goldenseal (Hydrastis) raise concerns of herbdrug interaction. DMPK studies of other Ranunculaceae genera, e.g., Nigella, Delphinium, Aconitum, Trollius, and Coptis, are also rapidly increasing and becoming more and more clinically relevant. In this contribution, we highlight the up-to-date awareness, as well as the challenges around the DMPK-related issues in optimization of drug development and clinical practice of Ranunculaceae compounds. Herb-herb interaction of Ranunculaceae herb-containing traditional Chinese medicine (TCM) formula could significantly influence the in vivo pharmacokinetic behavior of compounds thereof, which may partially explain the complicated therapeutic mechanism of TCM formula. Although progress has been made on revealing the absorption, distribution, metabolism, excretion and toxicity (ADME/T) of Ranunculaceae compounds, there is a lack of DMPK studies of traditional medicinal genera Aquilegia, Thalictrum and Clematis. Fluorescent probe compounds could be promising substrate, inhibitor and/or inducer in future DMPK studies of Ranunculaceae compounds. A better understanding of the important herb-drug/herb-herb interactions, bioavailability and metabolomics aspects of Ranunculaceae compounds will bolster future natural product-based drug design and the comprehensive investigation of inter-individual inconsistency of drug metabolism.

Highly active antiretroviral therapy (HAART) and direct acting antiviral agents (DAAs) are key elements in the effective pharmacotherapy of human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) respectively. These two chronic illnesses affect millions of persons at any given time, though only a select proportion has been eligible for successful treatment. With the development of newer, safer and more effective antiviral therapies it is expected that a greater proportion of those infected will have access to these life-saving therapies. However, it is also important to appreciate that this very population will also be subject to increased toxicities from these agents. In this review we outline the published nephrotoxic effects of select new agents used in the management of HIV and HCV, specifically commenting, where possible, on the role of epithelial organic transporters in explaining the said renal toxicities.