Recent publications
- Efficient and selective kidney targeting by chemically modified carbohydrate conjugates November 12, 2024We investigated a renal tubule-targeting carbohydrate (RENTAC) that can selectively deliver small-molecule and nucleic acid analogs to the proximal convoluted tubules of the kidney following systemic delivery in mice. We comprehensively evaluated anti-miR-21-peptide nucleic acid-RENTAC, and fluorophore-RENTAC conjugates in cell culture and in vivo. We established that RENTAC conjugates showed megalin- and cubilin-dependent endocytic uptake […]Vikas Kumar
- Evaluation of UCP1162, a potent propargyl-linked inhibitor of dihydrofolate reductase with potential application to cancer and autoimmune disease November 11, 2024Cellular resistance can limit the effectiveness of antifolate drugs for the treatment of cancer and autoimmune diseases. We examined the biochemical and cellular effects of a propargyl linked, non-classical antifolate UCP1162 that shows exceptional potency and resilience in the background of methotrexate resistance. UCP1162 inhibited the human DHFR enzyme with affinity and kinetics comparable to […]Didem Ozcan Tezgin
- Exploring the therapeutic potential of sγPNA-141: Pharmacodynamics and mechanistic insights during ischemic stroke recovery November 7, 2024MicroRNA-141-3p plays a detrimental role in the pathology of ischemic stroke, presenting a new target for stroke treatment. This study introduces and validates a novel class of peptide nucleic acid (PNA)-based miR-141-3p inhibitors known as serine gamma PNA-141 (sγPNA-141) for ischemic stroke treatment. After synthesis, physicochemical characterization, and nanoparticle encapsulation of sγPNA-141, we compared its […]Sanjeev Kumar Yadav
- Recent advances in mRNA-based cancer vaccines encoding immunostimulants and their delivery strategies October 22, 2024The high prevalence of drug resistance, relapse, and unfavorable response rate of conventional cancer therapies necessitate the development of more efficient treatment modalities. Immunotherapy represents a novel therapeutic approach to cancer treatment in which the immune system's potential is harnessed to recognize and eliminate tumor cells. mRNA cancer vaccines, as a burgeoning field of immunotherapy, […]Seyyed Majid Eslami
- Professor Lynne S. Taylor: Scientist, educator, and adventurer October 19, 2024This special edition of the Journal of Pharmaceutical Sciences is dedicated to Professor Lynne S. Taylor (Retter Distinguished Professor of Pharmacy, Department of Industrial and Molecular Pharmaceutics, Purdue University), to honor her distinguished career as a pharmaceutical scientist and educator. The goal of this commentary is to provide an overview of Professor Taylor's career path, […]Dana E Moseson
- Evaluation of the impact of the polymer end groups and molecular weight on in vitro and in vivo performances of PLGA based in situ forming implants for ketoprofen October 19, 2024In situ forming implants are appealing long-acting dosage forms for both preclinical and clinical applications due to their simple manufacturing process and easy delivery. This study aims to develop extended-release in situ forming solid implants for subcutaneous administration using two types of commercially available triblock poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) polymers, with […]Sanjib Saha
- Enhancing RNA inhibitory activity using clamp-G-modified nucleobases October 18, 2024We explore the potential of clamp-G nucleobase-modified peptide nucleic acids (cGPNAs) as microRNA and messenger RNA inhibitors. For proof of concept, we target miR-155, which is upregulated in diffuse large B cell lymphoma. cGPNA shows significant downregulation of miR-155 and the upregulation of its downstream targets in multiple lymphoma cell lines. Also, cGPNA treatment in […]Sai Pallavi Pradeep
- Enhanced Plasma Stability and Potency of Aryl/Acyloxy Prodrugs of a BTN3A1 Ligand October 16, 2024While ester-based phosphonate prodrugs excel at delivering payloads into cells, their instability in plasma is a hurdle for their advancement. Here, we synthesized new aryl/acyloxy prodrugs of a phosphonate BTN3A1 ligand. We evaluated their phosphoantigen potency by flow cytometry and ELISA and their plasma and cellular metabolism by LC-MS. These compounds displayed low nanomolar to […]Umed Singh
- 50th Anniversary Celebration Collection Special Section on New and Emerging Areas and Technologies in Drug Metabolism and Disposition, Part II-Editorial October 16, 2024No abstractXiao-Bo Zhong
- Probing hot spots of protein-protein interactions mediated by the safety-belt region of REV7 October 4, 2024REV7 is a HORMA (Hop1, Rev7, Mad2) family adaptor protein best known as an accessory subunit of the translesion synthesis (TLS) DNA polymerase ζ (Polζ). In this role, REV7 binds REV3, the catalytic subunit of Polζ, by locking REV7-binding motifs (RBMs) in REV3 underneath the REV7 safety-belt loop. The same mechanism is used by REV7 […]Radha Charan Dash
- Implant dynamics, inner structure, and their impact on drug release of in situ forming implants uncovered through CT imaging September 30, 2024In situ forming implants (ISFIs) composed of biodegradable polymers and biocompatible solvents are generally designed for sustained drug release. In this study, a non-invasive computed tomography (CT) imaging approach is used to achieve real time imaging of ISFIs in vivo and in vitro using leuprolide acetate in situ forming implant as a model drug product. […]Xinhao Lin
- The Particle Drifting Effect: A Combined Function of Colloidal and Drug Properties September 27, 2024The particle drifting effect, where nanosized colloidal drug particles overcome the diffusional resistance of the aqueous boundary layer adjacent to the intestinal wall and increase drug absorption rates, is drawing increasing attention in pharmaceutical research. However, mechanistic understanding and accurate prediction of the particle drifting effect remain lacking. In this study, we systematically evaluated the […]Da Hye Yang
- Impact of controlled ice nucleation on intracellular dehydration, ice formation and their implications on T cell freeze-thaw viability September 12, 2024Cryopreservation is important in manufacturing of cell therapy products, influencing their safety and effectiveness. During freezing and thawing, intracellular events such as dehydration and ice formation can impact cell viability. In this study, the impact of controlling the ice nucleation temperature on intracellular events and viability were investigated. A model T cell line, Jurkat cells, […]Nirnoy Dan
- Development of an automated 3D high content cell screening platform for organoid phenotyping September 8, 2024The use of organoid models in biomedical research has grown substantially since their inception. As they gain popularity among scientists seeking more complex and biologically relevant systems, there is a direct need to expand and clarify potential uses of such systems in diverse experimental contexts. Herein we outline a high-content screening (HCS) platform that allows […]Suleyman B Bozal
- Connecting dots between nucleotide biosynthesis and DNA lesion repair/bypass in cancer August 27, 2024Purine and pyrimidine nucleotides are crucial building blocks for the survival of cells, and there are layers of pathways to make sure a stable supply of them including de novo nucleotide biosynthesis. Fast-growing cells including cancer cells have high demand for nucleotide, and they highly utilize the nucleotide biosynthesis pathways. Due to the nature of […]Jackson C Lin
- Growth Mechanisms of Amorphous Nanoparticles in Solution and During Heat Drying August 26, 2024The purpose of this study was twofold: to identify the growth mechanisms of amorphous nanoparticles in solution and during the drying process at high temperatures, and to guide the process condition and stabilizer selection for amorphous nanoparticle formulations. In contrast to nanocrystals that are mostly mechanically robust, amorphous nanoparticles tend to undergo deformation under stress. […]Akshay Narula
- Novel dissolution methods for drug release testing of Long-Acting injectables August 25, 2024Long-acting parenteral drug products are a popular choice for therapeutic areas requiring long term treatment. These products range from dispersed systems such as drug suspensions and polymeric microspheres to in situ forming polymeric implants. The lack of reliable drug release testing methods for these drug products not only impedes the development of new drug products […]Nilesh Malavia
- Correlations of Long Noncoding RNA HNF4A-AS1 Alternative Transcripts with Liver Diseases and Drug Metabolism August 21, 2024Hepatocyte nuclear factor 4 alpha antisense 1 (HNF4A-AS1) is a long noncoding RNA (lncRNA) gene physically located next to the transcription factor HNF4A gene in the human genome. Its transcription products have been reported to inhibit the progression of hepatocellular carcinoma (HCC) and negatively regulate the expression of cytochrome P450s (CYPs), including CYP1A2, 2B6, 2C9, […]Jing Jin
- Parenteral iron nutrition: Iron dextran-poloxamer thermosensitive hydrogel for prolonged intramuscular iron supplementation August 9, 2024The objective of this study was to evaluate the potential of novel poloxamer thermosensitive hydrogels (PTHs) formulations for prolonged release of iron dextran particles (IDP) for intramuscular (IM) injection. The thermosensitive behaviour helps to avoid hepcidin overexpression and toxicity by releasing IDPs without iron accumulation in injection or deposit sites. We hypothesized that novel PTH […]Emerson Durán
- Synthesis and evaluation of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate analogs as competitive partial agonists of butyrophilin 3A1 July 19, 2024Phosphoantigens (pAgs) induce conformational changes after binding to the intracellular region of BTN3A1 which result in its clustering with BTN2A1, forming an activating ligand for the Vγ9Vδ2 T cell receptor. Here, we designed a small panel of bulky analogs of the prototypical pAg (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) that contain an aromatic ring attached to the C-3 […]Rohit Singh