Recent publications
- Tailoring drug release from long-acting contraceptive levonorgestrel intrauterine systems April 22, 2024The wide array of polydimethylsiloxane (PDMS) variants available on the market, coupled with the intricate combination of additives in silicone polymers, and the incomplete understanding of drug release behavior make formulation development of levonorgestrel intrauterine systems (LNG-IUSs) formidable. Accordingly, the objectives of this work were to investigate the impact of excipients on formulation attributes and […]Suraj Fanse
- Numerical study of drop dynamics for inkjet based 3D printing of pharmaceutical tablets March 24, 2024Interest in 3D printing has been growing rapidly especially in pharmaceutical industry due to its multiple advantages such as manufacturing versatility, personalization of medicine, scalability, and cost effectiveness. Inkjet based 3D printing gained special attention after FDA's approval of Spritam® manufactured by Aprecia pharmaceuticals in 2015. The precision and printing efficiency of 3D printing is […]Tanu Mehta
- State of the Art of Silica Nanoparticles: An Overview on Biodistribution and Preclinical Toxicity Studies March 22, 2024Over the past few years, nanoparticles have drawn particular attention in designing and developing drug delivery systems due to their distinctive advantages like improved pharmacokinetics, reduced toxicity, and specificity. Along with other successful nanosystems, silica nanoparticles (SNPs) have shown promising effects for therapeutic and diagnostic purposes. These nanoparticles are of great significance owing to their […]Joshua Yu
- Studying the ssDNA loaded adeno-associated virus aggregation using coarse-grained molecular dynamics simulations March 14, 2024The aggregation of adeno-associated viral (AAV) capsids in an aqueous environment was investigated via coarse-grained molecular dynamics (CG-MD) simulations. The primary driving force and mechanism of the aggregation were investigated with or without single-strand DNA (ssDNA) loaded at various process temperatures. Capsid aggregation appeared to involve multiple residue interactions (i.e., hydrophobic, polar and charged residues) […]Tibo Duran
- Investigating Protein-Protein Interactions of Autophagy-Involved TNIP1 March 5, 2024Myriad proteins are involved in the process of autophagy, which they participate in via their protein-protein interactions (PPI). Herein we outline a methodology for examining such interactions utilizing the case of intrinsically disordered protein (IDP) TNIP1 and its interaction with linear M1-linked polyubiquitin. This includes methods for recombinant production, purification, immuno-identification, and analysis of an […]Michael L Samulevich
- Novel insights into the role of translesion synthesis polymerase in DNA incorporation and bypass of 5-fluorouracil in colorectal cancer February 28, 20245-Fluorouracil (5-FU) is the first-line chemotherapeutic agent in colorectal cancer, and resistance to 5-FU easily emerges. One of the mechanisms of drug action and resistance of 5-FU is through DNA incorporation. Our quantitative reverse-transcription PCR data showed that one of the translesion synthesis (TLS) DNA polymerases, DNA polymerase η (polη), was upregulated within 72 h […]Jameson R Averill
- Hyper-spectra imaging analysis of PLGA microspheres via machine learning enhanced Raman spectroscopy February 3, 2024Long-acting injectables (LAI) offer a cost-effective and patient-centric approach by reducing pill burden and improving compliance, leading to better treatment outcomes. Among various types of long-acting injectables, poly (lactic-co-glycolic acid) (PLGA) microspheres have been extensively investigated and reported in the literature. However, microsphere formulation development is still challenging due to the complexity of PLGA polymer, […]Minghe Li
- Impact of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) on the expression and function of hepatobiliary transporters: A comprehensive mechanistic review January 31, 2024The liver plays a central role in the biotransformation and disposition of endogenous molecules and xenobiotics. In addition to drug-metabolizing enzymes, transporter proteins are key determinants of drug hepatic clearance. Hepatic transporters are transmembrane proteins that facilitate the movement of chemicals between sinusoidal blood and hepatocytes. Other drug transporters translocate molecules from hepatocytes into bile […]Ankit P Laddha
- Antitumor efficacy of a sequence-specific DNA-targeted γPNA-based c-Myc inhibitor January 6, 2024Targeting oncogenes at the genomic DNA level can open new avenues for precision medicine. Significant efforts are ongoing to target oncogenes using RNA-targeted and protein-targeted platforms, but no progress has been made to target genomic DNA for cancer therapy. Here, we introduce a gamma peptide nucleic acid (γPNA)-based genomic DNA-targeted platform to silence oncogenes in […]Shipra Malik
- The long noncoding RNA HNF1A-AS1 with dual functions in the regulation of cytochrome P450 3A4 January 4, 2024Cytochrome P450 3A4 (CYP3A4) is the most important and abundant drug-metabolizing enzyme in the human liver. Inter-individual differences in the expression and activity of CYP3A4 affect clinical and precision medicine. Increasing evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in the regulation of CYP3A4 expression. Here, we showed that lncRNA hepatocyte nuclear factor […]Yiting Wang
- Evaluation of mucosal immune profile associated with Zileuton nanocrystal-formulated BCS-II drug upon oral administration in Sprague Dawley rats December 26, 2023Nanocrystal drug formulation involves several critical manufacturing procedures that result in complex structures to improve drug solubility, dissolution, bioavailability, and consequently the efficacy of poorly soluble Biopharmaceutics Classification System (BCS) II and IV drugs. Nanocrystal formulation of an already approved oral drug may need additional immunotoxic assessment due to changes in the physical properties of […]Sangeeta Khare
- Head-to-head comparison of <em>in vitro</em> and <em>in vivo</em> efficacy of pHLIP-conjugated anti-seed gamma peptide nucleic acids December 25, 2023Gamma peptide nucleic acids (γPNAs) have recently garnered attention in diverse therapeutic and diagnostic applications. Serine and diethylene-glycol-containing γPNAs have been tested for numerous RNA-targeting purposes. Here, we comprehensively evaluated the in vitro and in vivo efficacy of pH-low insertion peptide (pHLIP)-conjugated serine and diethylene-based γPNAs. pHLIP targets only the acidic tumor microenvironment and not […]Karishma Dhuri
- Complex oiling-out behavior of procaine with stable and metastable liquid phases December 14, 2023During the crystallization of a solute from solvent(s), spontaneous liquid-liquid phase separation (LLPS) might occur, under certain conditions. This phenomenon, colloquially referred to as "oiling-out" in the pharmaceutical industry, often leads to undesired outcomes, including undesired particle properties, encrustation, ineffective impurity rejection, and excessively long process time. Therefore, it is critical to understand the thermodynamic […]Da Hye Yang
- A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing November 22, 2023Butyrophilin (BTN)-3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding […]Mohindar M Karunakaran
- Diester Prodrugs of a Phosphonate Butyrophilin Ligand Display Improved Cell Potency, Plasma Stability, and Payload Internalization November 7, 2023Activation of Vγ9Vδ2 T cells with butyrophilin 3A1 (BTN3A1) agonists such as (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) has the potential to boost the immune response. Because HMBPP is highly charged and metabolically unstable, prodrugs may be needed to overcome these liabilities, but the prodrugs themselves may be limited by slow payload release or low plasma stability. To […]Umed Singh
- HMGB2 is a potential diagnostic marker and therapeutic target for liver fibrosis and cirrhosis November 6, 2023CONCLUSION: We conclude that HMGB2 is indispensable for stellate cell activation. Therefore, HMGB2 may serve as a potential therapeutic target to prevent HSC activation during chronic liver injury. The blood HMGB2 level may also serve as a potential diagnostic marker to detect early stage of liver fibrosis and cirrhosis in humans.Yi Huang
- DNA recognition and induced genome modification by a hydroxymethyl-γ tail-clamp peptide nucleic acid November 3, 2023Peptide nucleic acids (PNAs) can target and stimulate recombination reactions in genomic DNA. We have reported that γPNA oligomers possessing the diethylene glycol γ-substituent show improved efficacy over unmodified PNAs in stimulating recombination-induced gene modification. However, this structural modification poses a challenge because of the inherent racemization risk in O-alkylation of the precursory serine side […]Stanley N Oyaghire
- The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement October 21, 2023Despite the thousands of lives lost during the ongoing opioid crisis, a scarcity of new and effective clinical treatments for opioid use disorder (OUD) remains. To address this unmet need, some researchers have turned to dissociative and psychedelic drugs to treat multiple psychiatric conditions. In particular, low doses of ketamine have been shown to attenuate […]Caryssa R Drinkuth
- Mitigation of Tribocharging in Pharmaceutical Powders using Surface Modified V-Blenders October 11, 2023INTRODUCTION: The pharmaceutical industry involves handling of powders on a large scale for manufacturing of solid dosage forms such as tablets and capsules constituting about 85% of the dosage forms. During this manufacturing process, powders get electrostatically charged due to numerous particle-particle and particle-equipment wall collisions. Most of the pharmaceutical powders are insulators in nature […]Tanu Mehta
- ASO drug Qalsody (tofersen) targets amyotrophic lateral sclerosis September 14, 2023Trends Pharmacol Sci. 2023 Dec;44(12):1043-1044. doi: 10.1016/j.tips.2023.08.008. Epub 2023 Sep 12.ABSTRACT STRUCTURE: Tofersen, an antisense oligonucleotide (ASO) drug, is a 20-base residue with an RNA-DNA-RNA (5-10-5) gapmer mixed backbone oligonucleotide. Within the molecule, there are nineteen inter-nucleotide linkages, with fifteen of them being 3’-O to 5’-O phosphorothioate diesters and the remaining four being 3’-O to […]Jing Jin