Enhanced Oral Efficacy of Semaglutide via an Ionic Nanocomplex with Organometallic Phyllosilicate in Type 2 Diabetic Rats.

This study aimed to develop an effective oral formulation of semaglutide, a glucagon-like peptide-1 receptor agonist, using an organometallic phyllosilicate-based colonic delivery system. The core nanocomplex (AMP-Sema) of 3-aminopropyl-functionalized magnesium phyllosilicate (AMP) and semaglutide was prepared via electrostatic interactions. Subsequently, AMP-Sema was coated with a polymer showing pH-dependent solubility (Eudragit S100) for preferential colonic delivery.

Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis Mice.

MT-102 is a new anti-inflammatory agent derived from and . Its therapeutic potential is hindered by low aqueous solubility, impacting its in vivo efficacy. Therefore, this study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) for MT-102 to enhance its oral efficacy in treating ulcerative colitis.

Organometallic Phyllosilicate-Gold Nanocomplex: An Effective Oral Delivery System of Methotrexate for Enhanced in vivo Efficacy Against Colorectal Cancer.

Purpose: Oral administration, although convenient and preferred for treating colorectal cancer (CRC), faces challenges due to limited CRC-related intestinal positioning and a dense mucus barrier. In the present study, a gold-nanoparticle decorated-organometallic phyllosilicate nanocomposite (AC-Au), with a pH-dependent surface coating, was employed for more effective oral delivery of anticancer drugs to treat CRC.

Methods: The organometallic AC-Au was synthesized using the in-situ sol-gel method.

Discovery of a novel BLT2 antagonist for the treatment of inflammatory airway diseases.

Leukotriene B4 (LTB4) is a potent chemoattractant that can recruit and activate immune cells such as neutrophils, eosinophils, and monocytes to sites of inflammation. Excessive production of LTB4 has been linked to acute and chronic inflammatory diseases, including asthma, rheumatoid arthritis, and psoriasis. Inhibiting the binding of LTB4 to its receptors, BLT1 and BLT2, is a potential strategy for treating these conditions.

Correction to "Rational Chemical Design of Molecular Glue Degraders".

[This corrects the article DOI: 10.1021/acscentsci.2c01317.

Fabrication and Evaluation of a pH-Responsive Nanocomposite-Based Colonic Delivery System for Improving the Oral Efficacy of Liraglutide.

Purpose: Oral administration of liraglutide, a protein drug, suffers from low intestinal absorption and instability in the gastrointestinal tract, resulting in low bioavailability. The present study aimed to develop a pH-responsive nanocomposite based-colonic delivery system to improve the oral efficacy of liraglutide.

Methods: Nanocomplex (AC-Lira) between aminoclay and liraglutide was prepared by a spontaneous self-assembly.

Rational Chemical Design of Molecular Glue Degraders.

Targeted protein degradation with molecular glue degraders has arisen as a powerful therapeutic modality for eliminating classically undruggable disease-causing proteins through proteasome-mediated degradation. However, we currently lack rational chemical design principles for converting protein-targeting ligands into molecular glue degraders. To overcome this challenge, we sought to identify a transposable chemical handle that would convert protein-targeting ligands into molecular degraders of their corresponding targets.

Quantitative analysis of therapeutic proteins in biological fluids: recent advancement in analytical techniques.

Pharmaceutical application of therapeutic proteins has been continuously expanded for the treatment of various diseases. Efficient and reliable bioanalytical methods are essential to expedite the identification and successful clinical development of therapeutic proteins. In particular, selective quantitative assays in a high-throughput format are critical for the pharmacokinetic and pharmacodynamic evaluation of protein drugs and to meet the regulatory requirements for new drug approval.

Aminoclay Nanoparticles Induce Anti-Inflammatory Dendritic Cells to Attenuate LPS-Elicited Pro-Inflammatory Immune Responses.

Although 3-aminopropyl functionalized magnesium phyllosilicate nanoparticles (hereafter aminoclay nanoparticles, ACNs) are well-known nanomaterials employed as drug carriers, their effects on immune cells remain unclear. To address this issue, we explored murine dendritic cells (DCs) as these cells belong to the innate arm of the immune system and function as antigen-presenting cells to elicit adaptive immune responses. We examined the in vitro effects of ACNs on DCs isolated from B6 mice.

Site-selective oral delivery of therapeutic antibodies to the inflamed colon a folic acid-grafted organic/inorganic hybrid nanocomposite system.

This study aimed to develop a pH-responsive folic acid-grafted organic/inorganic hybrid nanocomposite system for site-selective oral delivery of therapeutic antibodies. A folic acid-grafted aminoclay (FA-AC) was prepared an sol‒gel method. Then, a drug-loaded nanocomplex was prepared the electrostatic interaction of FA-AC with infliximab (IFX), a model antibody, and coated with Eudragit® S100 (EFA-AC-IFX).

Lipid/Clay-Based Solid Dispersion Formulation for Improving the Oral Bioavailability of Curcumin.

This study was conducted to develop a lipid/clay-based solid dispersion (LSD) formulation to enhance the dissolution and oral bioavailability of poorly soluble curcumin. Krill oil and aminoclay were used as a lipid and a stabilizer, respectively, and LSD formulations of curcumin were prepared by an antisolvent precipitation method combined with freeze-drying process. Based on the dissolution profiles, the optimal composition of LSD was determined at the weight ratio of curcumin: krill oil: aminoclay of 1:5:5 in the presence of 0.

Enhanced Oral Bioavailability of MT-102, a New Anti-inflammatory Agent, via a Ternary Solid Dispersion Formulation.

This study aimed to develop a solid dispersion (SD) of MT-102, a new anti-inflammatory agent, to improve its oral bioavailability. The ternary SD formulations of MT-102 (a poorly soluble extract of and ) were prepared using a solvent evaporation method with various drug/excipient ratios. Following that, the effectiveness of various SDs as an oral formulation of MT-102 was investigated using indirubin as a marker component.

Functional ligands for improving anticancer drug therapy: current status and applications to drug delivery systems.

Conventional chemotherapy lacking target selectivity often leads to severe side effects, limiting the effectiveness of chemotherapy. Therefore, drug delivery systems ensuring both selective drug release and efficient intracellular uptake at the target sites are highly demanded in chemotherapy to improve the quality of life of patients with low toxicity. One of the effective approaches for tumor-selective drug delivery is the adoption of functional ligands that can interact with specific receptors overexpressed in malignant cancer cells.

Enhanced Bioavailability of AC1497, a Novel Anticancer Drug Candidate, via a Self-Nanoemulsifying Drug Delivery System.

AC1497 is an effective dual inhibitor of malate dehydrogenase 1 and 2 targeting cancer metabolism. However, its poor aqueous solubility results in low bioavailability, limiting its clinical development. This study was conducted to develop an effective self-nanoemulsifying drug delivery system (SNEDDS) of AC1497 to improve its oral absorption.

A Scalable Implementation of Anonymous Voting over Ethereum Blockchain.

We considered scalable anonymous voting on the Ethereum blockchain. We identified three major bottlenecks in implementation: (1) division overflow in encryption of voting values for anonymity; (2) large time complexity in tallying, which limited scalability in the number of candidates and voters; and (3) tallying failure due to "no votes" from registered voters. Previous schemes failed at tallying if one (or more) registered voters did not send encrypted voting values.

A Smart Contract-Based P2P Energy Trading System with Dynamic Pricing on Ethereum Blockchain.

We implement a peer-to-peer (P2P) energy trading system between prosumers and consumers using a smart contract on Ethereum blockchain. The smart contract resides on a blockchain shared by participants and hence guarantees exact execution of trade and keeps immutable transaction records. It removes high cost and overheads needed against hacking or tampering in traditional server-based P2P energy trade systems.

NITD-688, a pan-serotype inhibitor of the dengue virus NS4B protein, shows favorable pharmacokinetics and efficacy in preclinical animal models.

Dengue virus (DENV) is a mosquito-borne flavivirus that poses a threat to public health, yet no antiviral drug is available. We performed a high-throughput phenotypic screen using the Novartis compound library and identified candidate chemical inhibitors of DENV. This chemical series was optimized to improve properties such as anti-DENV potency and solubility.

Development of an M cell targeted nanocomposite system for effective oral protein delivery: preparation, in vitro and in vivo characterization.

Background: There is a strong need for non-invasive and patient-friendly delivery systems of protein drugs for long-term therapy. However, oral delivery of protein drugs is a big challenge due to many barriers including instability in the gastrointestinal (GI) tract and low permeability. To overcome the absorption barriers in GI tract and improve the patient compliance, this study aimed to develop an M cell targeted-nanocomposite delivery system of protein drugs.

DK-1108 exerts anti-inflammatory activity against phorbol 12-myristate 13-acetate-induced inflammation and protective effect against OVA-induced allergic asthma.

There is an increasing interest in natural products and their derivatives with therapeutic benefits and less side effects compared to steroid therapy. Benzofuran derivatives display biological effects including anti-inflammatory effects. The present study aims to investigate whether (3-(7-methoxy-2-p-tolyl benzofuran-5-yl) propan-1-ol) (DK-1108), new synthetic benzofuran compound exerts anti-asthmatic effects in vitro and in vivo.

A New Therapeutic Approach Using a Calcilytic (AXT914) for Postsurgical Hypoparathyroidism in Female Rats.

Postsurgical hypoparathyroidism is the most common complication of thyroid surgery. Conventional therapy with high-dose calcium and vitamin D can correct hypocalcemia but can increase the risk of hypercalciuria, renal stones, or ectopic calcification. The aim of the present study was to investigate the efficacy of a calcium-sensing receptor antagonist, also called a calcilytic (AXT914), in rat models of postsurgical hypoparathyroidism.

Enhanced oral delivery of insulin via the colon-targeted nanocomposite system of organoclay/glycol chitosan/EudragitS100.

This study aimed to develop a ternary nanocomposite system of organoclay, glycol-chitosan, and EudragitS100 as an effective colon targeted drug delivery carrier to enhance the oral absorption of insulin. A nanocomplex of insulin and aminoclay was prepared via spontaneous co-assembly, which was then coated with glycol-chitosan and Eudragit S100 (EGAC-Ins). The double coated nanocomplex, EGAC-Ins demonstrated a high entrapment efficiency of greater than 90% and a pH-dependent drug release.

Ternary nanocomposite carriers based on organic clay-lipid vesicles as an effective colon-targeted drug delivery system: preparation and in vitro/in vivo characterization.

This study aimed to develop a new colon-targeted drug delivery system via the preparation of ternary nanocomposite carriers based on organic polymer, aminoclay and lipid vesicles. Budesonide (Bud), an anti-inflammatory drug was chosen as a model drug and encapsulated into three different formulations: liposome (Bud-Lip), aminoclay-coated liposome (AC-Bud-Lip), and Eudragit S100-aminoclay double coated liposome (EAC-Bud-Lip). The formation of the aminoclay-lipid vesicle nanocomposite was confirmed by energy dispersive X-ray spectrum, transmission electron microscopy, and Fourier-transform infrared spectroscopy.

Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery.

Advancements in biotechnology and protein engineering expand the availability of various therapeutic proteins including vaccines, antibodies, hormones, and growth factors. In addition, protein drugs hold many therapeutic advantages over small synthetic drugs in terms of high specificity and activity. This has led to further R&D investment in protein-based drug products and an increased number of drug approvals for therapeutic proteins.

Development of pH-responsive organic-inorganic hybrid nanocomposites as an effective oral delivery system of protein drugs.

This research aimed to develop a pH-responsive organic-inorganic hybrid nanocomposite as an effective oral delivery system for protein drugs. Three different nanocomposites were prepared by using bovine serum albumin (BSA) as a model protein. A nanocomplex of BSA with 3-aminopropyl functionalized magnesium phyllosilicate (AC-BSA) was obtained via the spontaneous co-assembly and then sequentially coated with glycol-chitosan (GAC-BSA) and the pH sensitive polymer, Eudragit®L100-55 (EGAC-BSA).

Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization.

LW6 (3-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-4-hydroxy-benzoic acid methyl ester) is a potent inhibitor of drug efflux by the breast cancer resistance protein (BCRP). However, its poor aqueous solubility leads to low bioavailability, which currently limits in vivo applications. Therefore, the present study aimed to develop ternary solid dispersion (SD) formulations in order to enhance the aqueous solubility and dissolution rate of LW6.