Enzymatic functions are often altered during disease onset and progression, and therefore chemical–biological studies, which utilize chemical knowledge to discover novel protein functions, are often employed to find proteins with functions closely related to disease phenotypes. Such studies are known as forward chemical–biological approaches and form part of the emerging field of enzymomics (omics of enzymes). This review provides an overview of methodologies available for discovering and characterizing disease-related alterations of enzymatic functions and prospects for the future.

Significant progress has been achieved in the development of stimuli-responsive nanocarriers for drug delivery, diagnosis, and therapy. Various types of triggers are utilized in the development of nanocarrier delivery. Endogenous factors such as changes in pH, redox, gradient, and enzyme concentration which are linked to disease progression have been utilized for controlling biodistribution and releasing drugs from nanocarriers, as well as increasing subsequent pharmacological activity at the disease site. Nanocarriers which respond to artificially-induced exogenous factors (such as temperature, light, magnetic field, and ultrasound) have also been developed. This review aims to discuss recent advances in the design of stimuli-responsive nanocarriers which appear to have a promising future in medicine.

Targeting cancer cell-surface receptors is an attractive approach for cancer treatment and diagnosis. Peptides having high binding affinities to receptors overexpressed in cancer cells are useful because of their simple structure, low immunogenicity, and easy, cost-effective chemical synthesis. A number of peptide ligands have been developed for cancer cell-surface receptors and applied to nanoparticles with anticancer drugs, genes, small interfering RNAs (siRNAs), and molecular imaging agents. In particular, recent findings have revealed that peptide-modified PEGylated liposome-encapsulated drugs are effective in cancer-targeted therapy and cancer cell-specific imaging. This review discusses peptide-modified nanoparticles for drug delivery systems (DDS) and molecular imaging, focusing on peptide ligands for somatostatin receptors, integrin, transferrin receptor, human epidermal growth factor 2 (HER2), etc. In addition, methods to improve binding affinity or endosomal escape with spacer peptides and stimuli (internal and external) are discussed.

Gold nanorods are promising metals in several biomedical applications such as bioimaging, thermal therapy, and drug delivery. Gold nanorods have strong absorption bands in near-infrared (NIR) light region and show photothermal effects. Since NIR light can penetrate deeply into tissues, their unique optical, chemical, and biological properties have attracted considerable clinical interest. Gold nanorods are expected to act not only as on-demand thermal converters for photothermal therapy but also as mediators of a controlled drug-release system responding to light irradiation. In this review, we discuss current progress using gold nanorods as bioimaging platform, phototherapeutic agents, and drug delivery vehicles.

Photodynamic therapy is achieved by the combination of photosensitizers, harmless visible or near-infrared (NIR) light, and molecular oxygen (O₂). Photosensitizers transfer their absorbed light energy to O₂ to generate a major active species in photodynamic therapy, singlet oxygen. In this review, I will discuss the possibility of single-walled carbon nanotubes as NIR photosensitizers, while explaining the general photophysics and photochemistry underlying photodynamic therapy as well as summarizing recent advances in the purification technologies for single-walled carbon nanotubes to reduce their toxicity concerns.

Photodynamic therapy (PDT) is an emerging cancer treatment that uses photosensitizers (PS), along with light to activate them, resulting in oxidation of various biological components in cancer tissues. However, since most potential PS are solubilized and given as aqueous solution, PS is non-specifically distributed in the body, leading to the induction of various side effects in normal tissues that are exposed to daylight such as skin and eyes. To overcome the problem associated with non-specific in vivo disposition of PS, various approaches have been applied to develop safer dosage forms for PS with more efficient tumor delivery and lower disposition to normal tissues. Passive drug targeting to tumors with nanoparticulate formulations has been recognized as one of the potentially useful approaches to improve the poor tissue specificity of conventional cancer chemotherapy and this approach should also be applicable for more efficient tumor delivery of PS. In this review article, several issues concerning the efficacy of PDT using nanoparticle-based formulations are discussed and our recent attempts to temporally enhance the vascular permeability within tumors with photodynamic treatment for the better therapeutic outcome of nanoparticle-based therapy are introduced.

In this review, we have summarized evaluation methods for the analysis of external stimuli-mediated nucleic acid and gene delivery. Prior to reviewing these evaluation methods, we describe various delivery processes of nucleic acid and gene medicines (small interfering RNA (siRNA), micro RNA, mRNA, plasmid DNA, etc.), which include interaction with blood components, bio-distribution, disposition in the target tissue, cell entry, intracellular trafficking, nuclear localization, and dissociation from the carriers. Next, we discuss the advantages of external stimuli-mediated nucleic acid and gene delivery. External stimuli enable us to effectively deliver nucleic acids and genes to targeted regions. Evaluation methods are required to elucidate the behaviors of nucleic acid and gene medicines in the body. Quantitative analyses of the bio-distribution and in situ disposition in perfused organs, as well as visualization of bio-distribution, transgene expression in the body, and intracellular trafficking of nucleic acid and gene medicines, are all useful in evaluating not only the efficacy and safety of delivery, but also serve as guidelines for the further development of nucleic acid and gene medicines by elucidating delivery problems. Progress in evaluation methods, including tissue optical clearing and super resolution microscopy, will help to better elucidate the in vivo fate of nucleic acid and gene medicines.

Here, we propose a novel therapeutic concept named drug-navigated clearance system (DNCS), in which a “navigator” decreases the concentration of a target etiologic factor in the blood by steering it to an unusual metabolic pathway. The navigator is composed of protein A (ProA) and dextran sulfate (DexS) and it successfully navigated antibodies (ABs), a model etiologic factor of dilated cardiomyopathy, to hepatocytes in vitro in the presence of low-density lipoprotein (LDL). ProA captured the Fc region of the target antibody while the DexS bound to LDL via the well-known electrostatic interaction. The hepatocytes simultaneously took up LDL via the LDL-receptor and internalized the AB/ProA–DexS complex that was bound to LDL. Therefore, this process demonstrates our attempt to navigate the etiologic factor to an alternate target pathway such as the LDL salvage.

The purpose of this study was to perform self-healing encapsulation of ONO-1301, a long-acting prostacyclin agonist, into poly(lactide-co-glycolide) (PLGA) microspheres using the oil-in-water (o/w) emulsion solvent evaporation method in order to try to limit the initial burst release of drug. Adequate self-healing of PLGA seemed to be achieved by stirring during the evaporation of solvent at 40°C close to the glass transition temperature (T_g) of the polymer (40.1°C). The plasticizers dimethylphthalate (DEP) or tributyl O-acetylcitrate (TBAC), at concentrations of 0.1–1.0%, to the internal oleogeneous phase in the o/w emulsion system was effective in restricting the initial burst release of the prepared microspheres. The combination of a self-healing at T_g of the polymer and the addition of 1% of each plasticizer was ultimately found to be the most effective in restricting the initial burst release. It is suggested that this is due to the synergistic effect of smooth surface morphology promoted by self-healing at T_g of the polymer and a decrease of the T_g of PLGA caused by the addition of plasticizers.

Liposomal vaginal drug delivery systems are important strategy in the treatment of both topical and systemic diseases. The aim of this study was to develop a vaginal delivery system for benzydamine hydrochloride (BNZ) loaded liposomes dispersed into mucoadhesive gels. The delivery system was also designed for a once a day dosage and to obtain controlled release of the BNZ. For this purpose BNZ containing gel formulations using hydroxypropyl methylcellulose (HPMC) K100M and Carbopol^® 974P, which are composed of polymers that show promising potential as mucoadhesive vaginal delivery systems, were developed. In addition, a BNZ containing liposome formulation was developed for vaginal administration. To improve the vaginal retention time, liposome was incorporated in HPMC K100M and Carbopol^® 974P gel formulations. This system is called lipogel. The developed BNZ liposomes have a slightly negative zeta potential (−1.50±0.16 mV), a 2.25±0.009 µm particle size and a 34% entrapment efficiency. These gels and lipogels have appropriate pH, viscosity, textural properties and mucoadhesive value for vaginal administration. Lipogels were found to be the best formulations for in vitro diffusion and ex vivo mucoadhesion. The work of mucoadhesion obtained from liposomes was in the range of 0.027±0.045 and 0.030±0.017 mJ/cm², while the value obtained from lipogels was between 0.176±0.037 and 0.243±0.53 mJ/cm². N1 and N2 lipogel formulations diffused 57 and 67% of BNZ respectively at the end of 24 h. Moreover, a higher mucoadhesion, which increases drug residence time in comparison to liposomes, could improve BNZ efficacy. In conclusion, BNZ mucoadhesive vaginal lipogel formulations can be promising alternatives to traditional dosage forms for vaginal topical therapy.

The abnormal aggregation of amyloid β-peptide (Aβ) is central to the pathogenesis of Alzheimer’s disease, the major form of dementia. Aromatic π–π interactions have been suggested to play a crucial role in the aggregation of not only Aβ, but also other amyloidogenic proteins. In this study, each or all phenylalanine (Phe) residues at the 4th, 19th, and 20th positions of Aβ-(1–40) were substituted by hydrophobic cyclohexylalanine (Cha), which is sterically similar to Phe, but lacks π-electrons, to reveal effects of interactions involving π-electrons on the aggregation of Aβ both in aqueous solution and GM1-containing membranes. We found that each Cha substitution significantly inhibited fibril formation by Aβ, indicating a pivotal role of aromatic interactions. Furthermore, the Aβ analog with three Cha residues effectively retarded the fibrillation of the wild-type Aβ.

The suitability of apparatuses for the quality control of indomethacin (IND, 50 mg) compounded suppositories was evaluated and the effects of the type of suppository base on release profiles was investigated. The release characteristics of hydrophilic and lipophilic suppositories containing IND were compared using four types of dissolution methods: basket (RB), paddle (PD), dialysis tubing (DT) and flow-through cell (FTC). The release process was evaluated using the following model independent parameters: the mean dissolution time (MDT), cumulative percent of drug released (Q) at the end of the sampling time, and dissolution efficiency (DE). The fastest and most reproducible release profiles were observed for a hydrophilic base (macrogols), which resulted in more than 90% of the drug being released in 30 min using PD, RB and FTC. After 90 min, 90% of the total amount of the drug was released from a mixture of hydrophilic bases with a lipophilic base (macrogols and hard fat) in compendial dissolution methods and the mixture base was the second fastest only to the hydrophilic base. The slowest release profiles in each method were observed for the lipophilic base (hard fat). Poor drug release from any type of suppository base was noted using DT. Based on the results of the present study, FTC may be regarded as an adequate technique allowing sufficient discriminating power for the quality control of IND compounded suppositories.

Rutin, a major flavonoid glycoside found in many higher plants, was exposed at 25 kGy of γ-ray and produced three new hydroxymethylated products 2–4 in the C-ring by γ-irradiation. Structures of the new compounds, including absolute configurations, were elucidated based on spectroscopic interpretation (NMR, UV, [α]_D, MS, and circular dichroism (CD)). The new unusual rutin derivatives 2 and 3 exhibited significantly enhanced inhibitory effects against α-glucosidase with IC₅₀ values of 23.1±1.2 and 11.2±0.7 µM, respectively, when compared to the parent rutin.

A new 28-norlupane triterpenoid, 3-acetate-28-norlup-20(29)-en-3β-hydroxy-17β-hydroperoxide (1) and a new tirucallane triterpenoid, cornusalterin M (2), together with one known triterpenoid, 3-acetate-28-norlup-20(29)-en-3β,17β-diol (3), were isolated from a MeOH extract of the stems of Cornus walteri. The chemical structures of the new compounds (1 and 2) were elucidated based on comprehensive one- and two-dimensional (1D and 2D) NMR spectroscopic experiments and high resolution-electrospray ionization (HR-ESI)-MS. Among the isolates, compound 1 was a relatively rare triterpenoid identified as a 28-norlupane-type triterpene with a 17β-hydroperoxide group and compound 3 was previously reported but only as a synthetic product. The cytotoxic activities of the isolated compounds 1–3 were evaluated by determining their inhibitory effects on human tumor cell lines (A549 (non-small cell lung carcinoma), SK-OV-3 (ovary malignant ascites), SK-MEL-2 (skin melanoma), and HCT-15 (colon adenocarcinoma)).

Total synthesis of sphingofungin E and 4,5-di-epi-sphingofungin E was achieved from an intermediate same as that of myriocin and mycestericin D via antipodal stereoselective dihydroxylations.