Pharmacokinetics, toxicities, and tissue concentrations of belotecan sprayed by rotational intraperitoneal pressurized aerosol chemotherapy in a pig model.

Objective: We evaluated the pharmacokinetics, tissue concentrations, and toxicities of belotecan during rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) in pigs.

Methods: We sprayed belotecan in 10% and 30% of doses for intravenous chemotherapy in six pigs (cohort 1, n=3, 0.50 mg/m²; cohort 2, n=3, 1.

CKD-497 inhibits NF-kB signaling and ameliorates inflammation and pulmonary fibrosis in ovalbumin-induced asthma and particulate matter-induced airway inflammatory diseases.

Air pollution, allergens, and bacterial infections are major contributors to pathological respiratory disorders worldwide. CKD-497, derived from the rhizome of and the fruits of , is known for its ability to relieve cough and facilitate phlegm expectoration. However, its protective action against allergic asthma and fine dust-induced lung inflammation, along with its underlying mechanisms, have not been thoroughly investigated.

A Population Pharmacokinetic Study to Compare a Novel Empagliflozin L-Proline Formulation with Its Conventional Formulation in Healthy Subjects.

Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that is commonly used for the treatment of type 2 diabetes mellitus (T2DM). CKD-370 was newly developed as a cocrystal formulation of empagliflozin with co-former L-proline, which has been confirmed to be bioequivalent in South Korea. This study aimed to quantify the differences in the absorption phase and pharmacokinetic (PK) parameters of two empagliflozin formulations in healthy subjects by using population PK analysis.

Development of a tetrahydroindazolone-based HDAC6 inhibitor with in-vivo anti-arthritic activity.

Histone deacetylase 6 (HDAC6) induces the expression of pro-inflammatory cytokines in macrophages; therefore, HDAC inhibitors may be beneficial for the treatment of macrophage-associated immune disorders and chronic inflammatory diseases, including atherosclerosis and rheumatoid arthritis. Structure-activity relationship studies were conducted on various phenyl hydroxamate HDAC6 inhibitors with indolone/indazolone-based bi- or tricyclic ring moieties as the cap group aiming to develop novel anti-arthritic drug candidates. Several compounds exhibited nanomolar activity and HDAC6 selectivity greater than 500-fold over HDAC1.

Comparison of the Pharmacokinetics, Safety, and Tolerability of Two Empagliflozin Formulations in Healthy Korean Subjects.

Purpose: Empagliflozin is a sodium-glucose cotransporter 2 inhibitor that is commonly used for the treatment of type 2 diabetes mellitus. As cocrystal formulation can improve the chemical properties of drugs, CKD-370 was newly developed as a cocrystal formulation of empagliflozin with solvate L-proline. This study aimed to compare the pharmacokinetics, safety, and tolerability of these two empagliflozin formulations in healthy Korean subjects.

Pharmacokinetic Comparison Between a Fixed-Dose Combination of Empagliflozin L-Proline/Metformin and Empagliflozin/Metformin in Healthy Korean Subjects.

Empagliflozin and metformin are oral antidiabetic drugs commonly used to treat type 2 diabetes mellitus as a combination therapy. This study aimed to compare the pharmacokinetics and safety of a newly developed fixed-dose combination of 5-mg empagliflozin L-proline and 1000-mg metformin with the reference drug. A randomized, open-label, single-dose, 2-period, 2-treatment, crossover study was conducted in healthy Korean subjects.

Effects of Hepatic Impairment on the Pharmacokinetic Profile and Safety of Lobeglitazone.

In this open-label, single-dose, parallel-group study, we compared the pharmacokinetic profile and safety of lobeglitazone, a thiazolidinedione acting as an agonist for peroxisome proliferator-activated receptors, in patients with hepatic impairment (HI) and healthy matched controls for age, sex, and body weight. After a single oral dose of lobeglitazone (0.5 mg), the lobeglitazone (parent drug) and M7 (major metabolite) plasma concentrations and pharmacokinetic parameters were analyzed and compared between the HI patient groups and healthy matched control groups.

Neural stem cells derived from human midbrain organoids as a stable source for treating Parkinson's disease: Midbrain organoid-NSCs (Og-NSC) as a stable source for PD treatment.

Successful clinical translation of stem cell-based therapy largely relies on the scalable and reproducible preparation of donor cells with potent therapeutic capacities. In this study, midbrain organoids were yielded from human pluripotent stem cells (hPSCs) to prepare cells for Parkinson's disease (PD) therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into midbrain-type dopamine(mDA) neurons, and an unprecedentedly high proportion expressed midbrain-specific factors, with relatively low cell line and batch-to-batch variations.

Polyphyllin D Shows Anticancer Effect through a Selective Inhibition of Src Homology Region 2-Containing Protein Tyrosine Phosphatase-2 (SHP2).

Natural products have continued to offer tremendous opportunities for drug development, as they have long been used in traditional medicinal systems. SHP2 has served as an anticancer target. To identify novel SHP2 inhibitors with potential anticancer activity, we screened a library containing 658 natural products.

The safety, pharmacodynamics, and pharmacokinetics of immediate-release formulation containing esomeprazole 20 mg/sodium bicarbonate 800 mg in healthy adult male.

Background: Esomeprazole is the most effective treatment for acid-related disorders and is widely used with enteric coating due to rapid degradation in the acidic environment. However, the enteric-coated formulation delays absorption and onset of action. To overcome this limitation, an immediate-release formulation containing esomeprazole 20 mg and sodium bicarbonate 800 mg (IR-ESO) was developed.

Liquid crystalline drug delivery vehicles for oral and IV/subcutaneous administration of poorly soluble (and soluble) drugs.

Poorly soluble drug molecules often have low bioavailability issues and absorption problems in the clinical setting. As the number of poorly soluble drugs increases from discovery, developing technologies to enhance their solubility, while also controlling their release is one of the many challenges facing the pharmaceutical industry today. Liquid crystalline systems, nanoparticulate or macro-matrix, self-assemble in the presence of an aqueous environment and can provide a solubility enhancement, while also controlling the drug release rate.

Practical and Sustainable Synthesis of Optically Pure Levocabastine, a H₁ Receptor Antagonist.

A practical and sustainable method for the synthesis of levocabastine hydrochloride (), a H₁ receptor antagonist for the treatment of allergic conjunctivitis, that can be applied to the industrial production of the compound has been developed. Substantial improvements over the previously reported procedure are achieved via efficient preparation of an optically active key intermediate () without chiral resolution and with a more effective detosylation, which complements the previous procedure. Notably, our process requires no chromatographic purification and provides levocabastine hydrochloride in greater than 99.

The in vivo transformation and pharmacokinetic properties of a liquid crystalline drug delivery system.

A liquid crystalline (LC) system, composed of phosphatidylcholine, sorbitan monoleate, and tocopherol acetate, was investigated to understand the in vivo transformation after subcutaneous injection, coupled with the physicochemical and pharmacokinetic properties of the formulation. The rat model was utilized to monitor a pseudo-time course transformation from a precursor LC formulation to the LC matrix, coupled with the blood concentration profiles of the formulations containing leuprolide acetate. Three formulations that result in the H phase, demonstrating dissimilar in vitro release profiles, were used.

HDAC6 Inhibitors Rescued the Defective Axonal Mitochondrial Movement in Motor Neurons Derived from the Induced Pluripotent Stem Cells of Peripheral Neuropathy Patients with Mutation.

The Charcot-Marie-Tooth disease 2F (CMT2F) and distal hereditary motor neuropathy 2B (dHMN2B) are caused by autosomal dominantly inherited mutations of the heat shock 27 kDa protein 1 () gene and there are no specific therapies available yet. Here, we assessed the potential therapeutic effect of HDAC6 inhibitors on peripheral neuropathy with mutation using in vitro model of motor neurons derived from induced pluripotent stem cells (iPSCs) of CMT2F and dHMN2B patients. The absolute velocity of mitochondrial movements and the percentage of moving mitochondria in axons were lower both in CMT2F-motor neurons and in dHMN2B-motor neurons than those in controls, and the severity of the defective mitochondrial movement was different between the two disease models.

Pharmacokinetics, pharmacodynamics and safety of CKD-519, a CETP inhibitor, in healthy subjects.

CKD-519 is a selective and potent cholesteryl ester transfer protein (CETP) inhibitor being developed for the treatment of dyslipidemia to raise high-density lipoprotein cholesterol. We investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of CKD-519 in healthy adult subjects. A randomized, double-blinded, placebo-controlled, single ascending dose study was performed.

Formulation and characterization of a liquid crystalline hexagonal mesophase region of phosphatidylcholine, sorbitan monooleate, and tocopherol acetate for sustained delivery of leuprolide acetate.

Although liquid crystal (LC) systems have been studied before, their utility in drug delivery applications has not been explored in depth. This study examined the development of a 1-month sustained release formulation of leuprolide acetate using an in situ-forming LC matrix. The phase progression upon water absorption was tested through construction of ternary phase diagrams of phosphatidylcholine, sorbitan monooleate, and tocopherol acetate (TA) at increasing water content.

A novel histone deacetylase inhibitor, CKD5, has potent anti-cancer effects in glioblastoma.

There have been extensive efforts to improve the outcome of glioblastoma, but the prognosis of this disease has not been significantly altered to date. Histone deacetylase inhibitors (HDACIs) have been evaluated as promising anti-cancer drugs and regulate cell growth, cell cycle arrest and apoptosis in glioblastoma. Here, we demonstrated the therapeutic efficacy of a novel pan-HDACI, 7-ureido-N-hydroxyheptanamide derivative (CKD5), compared with traditional pan-HDACIs, such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), in vitro and in vivo.

Vitamin D Receptor-Mediated Upregulation of CYP3A4 and MDR1 by Quercetin in Caco-2 cells.

To examine whether quercetin interacts with vitamin D receptor, we investigated the effects of quercetin on vitamin D receptor activity in human intestinal Caco-2 cells. The effects of quercetin on the expression of the vitamin D receptor target genes, vitamin D3 24-hydroxylase, cytochrome P450 3A4, multidrug resistance protein 1, and transient receptor potential vanilloid type 6 were measured using quantitative polymerase chain reaction. The vitamin D receptor siRNA was used to assess the involvement of the vitamin D receptor.

Gender differences in the hepatic elimination and pharmacokinetics of lobeglitazone in rats.

The pharmacokinetics of lobeglitazone (LB) was studied after intravenous administration at a dose of 1 mg/kg and oral administration at doses of 0.1, 1 and 10 mg/kg in male and female rats. The area under the plasma concentration-time curve from time zero to infinity (AUC ) after intravenous administration was approximately 7.

Tubulin inhibitor identification by bioactive conformation alignment pharmacophore-guided virtual screening.

Microtubules are important cellular component that are critical for proper cellular function. Microtubules are synthesized by polymerization of αβ tubulin heterodimers called protofilaments. Microtubule dynamics facilitate proper cell division during mitosis.

Chitosan-based hybrid nanocomplex for siRNA delivery and its application for cancer therapy.

Purpose: Chitosan, a natural and biocompatible cationic polymer, is an attractive carrier for small interfering RNA (siRNA) delivery. The purpose of this study was to develop a chitosan-based hybrid nanocomplex that exhibits enhanced physical stability in the bloodstream compared with conventional chitosan complexes. Hybrid nanocomplexes composed of chitosan, protamine, lecithin, and thiamine pyrophosphate were prepared for systemic delivery of survivin (SVN) siRNA.

A new injectable liquid crystal system for one month delivery of leuprolide.

An injectable liquid crystal-forming system (LCFS) was prepared by using sorbitan monooleate (SMO) as a new liquid crystal-forming material for injections, and its potential use of clinically available sustained-release formulation was evaluated. LCFS was prepared using SMO mixed with phosphatidyl choline and tocopherol acetate, and contained 3.75 mg of leuprolide acetate as a monthly dose in 90 μl in liquid form.

Carcinogenicity study of CKD-501, a novel dual peroxisome proliferator-activated receptors α and γ agonist, following oral administration to Sprague Dawley rats for 94-101 weeks.

CKD-501 is a peroxisome proliferator-activated receptor (PPAR) agonist. The current study was conducted in Sprague Dawley (SD) rats for 94-101 weeks to investigate the carcinogenic potential of CKD-501. 60 males received 0, 0.