A Data-Mining Approach for the Quantitative Assessment of Physicochemical Properties of Molecular Compounds in the Skin Flux.

This paper aimed to provide an insight into the mechanism of transdermal penetration of drug molecules with respect to their physicochemical properties, such as solubility (S), the presence of enantiomer (ET) and logarithm of octanol-water partition coefficient (log P), molecular weight (MW), and melting point (MP). Propionic acid derivatives were evaluated for their flux through full-thickness skin excised from hairless mice upon being delivered from silicone-based pressure-sensitive adhesive (PSA) matrices in the presence or absence of various enhancers. The skin fluxes of model compounds were calculated based on the data obtained using the method engaged with the diffusion cell system.

A practical guide to the development of microneedle systems - In clinical trials or on the market.

Microneedle systems are a rapidly growing and promising technology for delivery of drugs, such as vaccines, small molecules, or biologics and for aesthetic skin treatment in local clinics; however, they remain relatively new from a regulatory perspective. There are strong demands for established procedures, test requirements for approval, and recent trends that industries/researchers related to microneedle systems can refer to. Some microneedle systems are commercially available, many are currently undergoing clinical trials, and some are pending approval for commercialization.

Enhancement of solubility and dissolution rate of baicalein, wogonin and oroxylin A extracted from Radix scutellariae.

Baicalein, wogonin, and oroxylin A are three major hydrophobic components in the extract of Radix scutellariae with wide spectrum of pharmacological applications. The purpose of this study was to enhance the solubility, dissolution rate and stability of baicalein, wogonin and oroxylin A by solid dispersion (SD) technique. SD of the extract with various polymers was prepared to select the best carrier.

Development of DH-I-180-3 loaded lipid nanoparticle for photodynamic therapy.

Photodynamic therapy (PDT) is a promising noninvasive treatment modality for cancer. Photosensitizer and specific wave length of light are the key component of PDT. DH-I-180-3, a second generation photosensitizer, was incorporated into lipid nanoparticle for simultaneous fluorescent imaging and targeting therapy.

Development of drug-in-adhesive patch formulations for transdermal delivery of fluoxetine: In vitro and in vivo evaluations.

The aim of this study was to develop drug-in adhesive (DIA) patch formulations for the transdermal delivery of fluoxetine (FX). The DIA patch formulations containing FX were prepared and optimized with various pressure sensitive adhesives, drug contents and enhancers. Among the various formulations, DuroTak 87-502B-based patch formulation containing 20% (w/w) FX with no enhancer was selected for in vivo pharmacokinetic study based on in vitro permeation studies using hairless mouse, rat and human cadaver skins.

Enhancement of solubility and dissolution of cilostazol by solid dispersion technique.

Cilostazol is practically insoluble in water and thus results in poor bioavailability. Only a few approaches have been reported for improving the bioavailability of cilostazol. Solid dispersion technique via solvent evaporation method was applied to improve the solubility and dissolution of cilostazol.

Size-controlled biodegradable nanoparticles: preparation and size-dependent cellular uptake and tumor cell growth inhibition.

Biodegradable nanoparticles with diameters below 1000nm are of great interest in the contexts of targeted delivery and imaging. In this study, we prepared PLGA nanoparticles with well-defined sizes of ∼70nm (NP70), ∼100nm (NP100), ∼200nm (NP200), ∼400nm (NP400), ∼600nm (NP600) and ∼1000nm (NP1000) using facile fabrication methods based on a nanoprecipitation and solvent evaporation techniques. The nanoparticles showed a narrow size distribution with high yield.

Prolyl isomerase Pin1 negatively regulates the stability of SUV39H1 to promote tumorigenesis in breast cancer.

Pin1, a conserved eukaryotic peptidyl-prolyl cis/trans isomerase, has profound effects on numerous key-signaling molecules, and its deregulation contributes to disease, particularly cancer. Although Pin1-mediated prolyl isomerization of protein servers as a regulatory switch in signaling pathways, the significance of proline isomerase activity in chromatin modifying complex remains unclear. Here, we identify Pin1 as a key negative regulator for suppressor of variegation 3-9 homologue 1 (SUV39H1) stability, a major methyltransferase responsible for histone H3 trimethylation on Lys9 (H3K9me3).

Effect of pressure sensitive adhesive and vehicles on permeation of terbinafine across porcine hoof membrane.

The purpose of this study was to investigate characteristics of transungual drug delivery and the feasibility of developing a drug-in-adhesive formulation of terbinafine. The permeation of terbinafine from a PSA matrix across porcine hoof membrane was determined using a plate containing poloxamer gel. The permeation rate of terbinafine across hairless mouse skin was evaluated using a flow-through diffusion cell system.

SIRT1-mediated FoxO1 deacetylation is essential for multidrug resistance-associated protein 2 expression in tamoxifen-resistant breast cancer cells.

Our previous studies have shown that multidrug resistance protein 2 (MRP2) is overexpressed in tamoxifen-resistant MCF-7 breast cancer cells (TAMR-MCF-7 cells) and forkhead box-containing protein, O subfamily1 (FoxO1), functions as a key regulator of multidrug resistance 1 (MDR1) gene transcription. This study aimed to investigate the role of FoxO1 in regulating MRP2 gene expression in TAMR-MCF-7 cells. The proximal promoter region of the human MRP2 gene contains four putative FoxO binding sites, and MRP2 gene transcription was stimulated by FoxO1 overexpression in MCF-7 cells.

Inhibitory effects of a new 1H-pyrrolo[3,2-c]pyridine derivative, KIST101029, on activator protein-1 activity and neoplastic cell transformation induced by insulin-like growth factor-1.

Diarylureas and diarylamides derivatives are reported to have antitumor activity. Encouraged by the interesting antiproliferative activity of diarylurea and diarylamide derivatives, we synthesized a new series of diarylureas and diarylamides containing pyrrolo[3,2-c]pyridine scaffold. In this study, we demonstrate that a N-(3-(4-benzamido-1H-pyrrolo[3,2-c]pyridin-1-yl)phenyl)-4-morpholino-3-(trifluoromethyl)benzamide, KIST101029, inhibits neoplastic cell transformation induced by insulin-like growth factor 1 (IGF-1) in mouse epidermal JB6 Cl41 cells.

Enhanced systemic exposure of saquinavir via the concomitant use of curcumin-loaded solid dispersion in rats.

The present study aimed to evaluate the effect of curcumin-loaded solid dispersion on the pharmacokinetics of saquinavir in rats. Solid dispersion (SD) formulation was prepared with Solutol® HS15 to improve the solubility and bioavailability of curcumin. Subsequently, its inhibition effect on P-gp mediated cellular efflux was examined by using NCI/ADR-RES cells overexpressing P-gp.

Application of Carbopol/PVP interpolymer complex to prepare mucoadhesive floating granule.

Novel mucoadhesive floating granule was prepared using Carbopol/PVP interpolymer complex to deliver hydrophilic drugs in a controlled manner. Acetaminophen was used as a model drug. Maximum floatability of the granules was obtained at the ratio of 1/1, where 95 % of the granules floated for 12 h.

Pin1 is required for ultraviolet A-stimulated cyclooxygenase-2 induction in mouse epidermal cells.

Ultraviolet A (UVA) radiation (320-400 nm) is considered a major cause of human skin photoaging and skin cancer. Overexpression of cyclooxygenase-2 (COX-2) leads to prostanoid formation in skin tissue, disturbs the balance between proliferation and apoptosis, and subsequently promotes tumorigenesis. The peptidyl-prolyl isomerase Pin1 is known to be overexpressed in most cancer cell types and plays an important role in oncogenesis.

Enhancement of solubility and dissolution rate of cryptotanshinone, tanshinone I and tanshinone IIA extracted from Salvia miltiorrhiza.

Cryptotanshinone, tanshinone I and tanshinone IIA are three major components in the extract of Salvia miltiorrhiza with pharmacological significance. However, their effective utilization is limited due to poor water solubility and bioavailability. Solid dispersion (SD) of the extract of Salvia miltiorrhiza was prepared to enhance solubility and dissolution of the three major components.

Identification of cis-acting elements and signaling components of high affinity IgE receptor that regulate the expression of cyclooxygenase-2.

Allergic and inflammatory responses are functionally linked through a cascade of signaling events that connect the aggregation of the high affinity IgE receptor (FcεRI) on mast cells and the initiation of cyclooxygenase-2 (COX-2) expression. In this study, we identified the cis-acting elements in the cox-2 promoter that control the expression of COX-2 in RBL-2H3 mast cells. We also investigated how the inflammatory reaction is controlled by the allergic reaction by determining the signaling components employed by FcεRI in the transcriptional regulation of cox-2.

Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier.

Solubility of curcumin at physiological pH was significantly increased by forming solid dispersion (SD) with Solutol® HS15. Since curcumin undergoes hydrolytic degradation, chemical stability study was conducted in pH 1.2, 6.

Influence of formulation variables in transdermal drug delivery system containing zolmitriptan.

The effects of different formulation variables including pressure sensitive adhesive (PSA), thickness of the matrix, solvent system, inclusion of crystallization inhibitor, loading amount of drug and enhancers on the transdermal absorption of zolmitriptan were investigated. Acrylic adhesive with hydroxyl functional group provided good adhesion force and high flux of zolmitriptan. Pseudopolymorphs of zolmitriptan were found to possess different solid-state properties that affected the permeation rate.

5'-Nitro-indirubinoxime inhibits epidermal growth factor- and phorbol ester-induced AP-1 activity and cell transformation through inhibition of phosphorylation of Pin1.

5'-Nitro-indirubinoxime (5'-NIO), a derivative of indirubin, exhibits anti-cancer activity in a variety of human cancer cells. However, the underlying molecular mechanisms and molecular target(s) of the chemopreventive activities of 5'-NIO remain unknown. Here, we report that 5'-NIO inhibited the epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic cell transformation of JB6 Cl41 mouse skin epidermal cells without any cytotoxic effects.

p-HPEA-EDA, a phenolic compound of virgin olive oil, activates AMP-activated protein kinase to inhibit carcinogenesis.

Phenolic constituents of virgin olive oil are reported to have antitumor activity. However, the underlying molecular mechanisms and specific target proteins of virgin olive oil remain to be elucidated. Here, we report that dialdehydic form of decarboxymethyl ligstroside aglycone (p-HPEA-EDA), a phenolic compound of virgin olive oil, inhibits tumor promoter-induced cell transformation in JB6 Cl41 cells and suppress cyclooxygenase-2 (COX-2) and tumorigenicity by adenosine monophosphate-activated protein kinase (AMPK) activation in HT-29 cells.

Recent advances in transdermal drug delivery.

Transdermal delivery of pharmacologically active agents has been extensively studied for the past 40 years. Despite the strong efforts, currently, only about 40 products are in market on about 20 drug molecules, due to the requirements that the patch area should be small enough for the patients to feel comfortable, and to the barrier properties of the stratum corneum. Various approaches to overcome the barrier function of skin through physical and chemical means have been broadly studied.

Doxorubicin-loaded solid lipid nanoparticles to overcome multidrug resistance in cancer therapy.

Unlabelled: In the present study we developed doxorubicin-loaded solid lipid nanoparticles (SLN-Dox) using biocompatible compounds, assessed the in vitro hemolytic effect, and examined their in vivo effects on drug retention and apoptosis intensity in P-glycoprotein-overexpressing MCF-7/ADR cells, a representative Dox-resistant breast cancer cell line. Our SLNs did not show hemolytic activity in human erythrocytes. In comparison with Dox, SLN-Dox efficiently enhanced apoptotic cell death through the higher accumulation of Dox in MCF-7/ADR cells.

Preparation and in vitro-in vivo evaluation of Witepsol H35 based self-nanoemulsifying drug delivery systems (SNEDDS) of coenzyme Q(10).

Coenzyme Q(10) (CoQ(10)) was formulated into self-nanoemulsifying drug delivery systems (SNEDDS) to overcome low bioavailability attributed to hydrophobic nature of the drug. Screening of oil phase, surfactants and co-surfactants were performed to select Witepsol H35, Solutol HS15 and Lauroglycol FCC, respectively. Ternary phase diagrams were drawn to identify nanoemulsifying region followed by optimization of SNEDDS formulation.

Enhancement of solubility and dissolution of coenzyme Q10 using solid dispersion formulation.

This study aimed to develop a stable solid dispersion of Coenzyme Q(10) (CoQ(10)) with high aqueous solubility and dissolution rate. Among various carriers screened, poloxamer 407 was most effective to form a superior solid dispersion of CoQ(10) having significantly enhanced solubility. Particularly, solid dispersion of CoQ(10) with poloxamer 407 in the weight ratio of 1:5 prepared by melting method enhanced the solubility of CoQ(10) to the greatest extent.