Multiphysics-Informed Pharmacokinetic Modeling of Systemic Exposure of Intramuscularly Injected LNPs

Molecular Pharmaceutics, Год журнала: 2023, Номер 20(12), С. 6162 - 6168

Опубликована: Ноя. 2, 2023

Lipid nanoparticle (LNP) constructs have been widely developed for gene therapy delivery. Understanding local absorption and presystemic clearance kinetics of LNPs, however, remains limited. This subsequently restrains the prediction assessment systemic exposure locally injected LNPs. As such, a multiscale computational approach was by integrating multiphysics simulation intramuscular LNPs with whole-body pharmacokinetics modeling, bridged lymphatic kinetic model. The overall framework enabled utilizing physiological parameters obtained from literature drug-related derived experiments. modeling predicted administered intramuscularly, high degree agreement between experimental data. Sensitivity analyses revealed that rate, pinocytosis lymph flow rate compartment had most significant impacts on Cmax. study yielded refreshing perspectives estimating exposures their safety effectiveness.

Язык: Английский

---

Characterization of mRNA-LNP structural features and mechanisms for enhanced mRNA vaccine immunogenicity

Journal of Controlled Release, Год журнала: 2024, Номер 376, С. 1288 - 1299

Опубликована: Ноя. 13, 2024

Язык: Английский

---

Study of the spatial strength distribution patterns and microstructure characteristics of ultra-fine tailings cemented paste backfill

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 2, 2025

Abstract In this study, the spatial distribution of mechanical strength ultra-fine tailings cemented paste backfill (UCPB) in underground stopes was examined, and micro-mechanism responsible for differences performance via changes particle deposition elucidated. To better understand phenomenon, we constructed a similar backfilling stope model using gold mine. We manufactured specimens at different locations conducted novel series tests, including uniaxial compressive strength, shear conventional triaxial to obtain parameters distributions. The UCPB were revealed examined along with original pore size Computer tomography (CT) scanning electron microscopy (SEM) observations before after failed that effect positions primary cause effect. pattern demonstrated material has an apparent Consequently, considering position relationship between filling mouth is crucial when designing adjacent mining rooms. This research may guide both study design.

Язык: Английский

---

Leveraging Model Master Files for Long-Acting Injectables

Pharmaceutical Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Abstract The U.S. Food and Drug Administration (FDA) the Center for Research on Complex Generics (CRCG) hosted a public workshop May 2–3, 2024, titled “Considerations Potential Regulatory Applications Model Master File (Lachaine et al Can J Psychiatry. 60:S40-S47, 2015)”. aimed to discuss application of (MMF) concept in regulatory submissions that contain model integrated evidence (MIE), improving sharing, standardization, consistency, efficiency. On Day 1, there was session dedicated MMF applications long-acting injectables (LAIs). This perspective summarizes presentations, panel discussion, small group discussion potential MMFs LAI product development, including case studies situations which can support submissions. scientific presentations discussed mechanistic physiologically based pharmacokinetic (PBPK), multiphysics simulation, population pharmacokinetics (popPK) models, as well utility model-integrated bioequivalence (MI-BE) framework. Additionally, challenges considerations implementing LAIs were groups. anticipated benefits are recognized among developers, industries, regulators. Graphical

Язык: Английский

---

Macroscopic transport models for drugs and vehicles in cancer tissues

Physical Sciences Reviews, Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

Abstract Modeling drug release in solid tumors is a convergence point between chemical engineering and medicine. Consequently, many studies have been conducted to unravel the mechanisms behind distribution after administration. In addition, several approaches explored, ranging from pharmacokinetic pharmacodynamic models microscopic transport through macroscopic models. This chapter focuses on latter, models, discusses how these can predict processes involved delivery, free form or vehicle transported. We start by presenting some of differentiating physiological parameters cancer tissues then main equations used for modeling, including fluid flow, mass transport, cell uptake. Also, use dimensionless explaining that control transportation will be examined. Lastly, final section explore process employed building geometries simulate tumors, as well current research being patient-specific simulations made using medical images.

Язык: Английский

---

Lipid Nanoparticles-Mediated mRNA Delivery to the Eye Affected by Ionizable Cationic Lipid

Molecular Pharmaceutics, Год журнала: 2025, Номер unknown

Опубликована: Май 7, 2025

Ionizable lipid serves as the key functional component in nanoparticles (LNPs) for efficient mRNA delivery. This study aims to systematically evaluate clinically approved ionizable DLin-MC3-DMA and SM102-based LNPs ocular delivery, with a comprehensive assessment of their physicochemical characteristics, delivery efficiency, biodistribution patterns within microenvironment. Enhanced green fluorescence protein or Luc encoding mRNA-loaded were formulated using microfluidic mixing technology characterized by dynamic light scattering, ζ-potential measurements, cryogenic transmission electron microscopy imaging. The two LNP systems different cationic lipids demonstrated distinct capabilities vitro transfection intraocular following intravitreal administration. Notably, SM102-LNPs exhibited superior performance compared MC3-LNPs, significantly higher efficiency retinal cells vitro, more expression minimal systemic distribution vivo. Safety that administration maintained excellent long-term biocompatibility throughout five-month period. establishes promising platform therapeutics.

Язык: Английский

---

Biophysical simulation of transcutaneous drug delivery for the rational design of hollow microneedle-based insulin infusion

Computers in Biology and Medicine, Год журнала: 2025, Номер 193, С. 110365 - 110365

Опубликована: Май 21, 2025

Язык: Английский

---

In vitro modeling of intramuscular injection site events

Expert Opinion on Drug Delivery, Год журнала: 2024, Номер 21(8), С. 1155 - 1173

Опубликована: Авг. 2, 2024

Intramuscular (IM) injections deliver a plethora of drugs. The majority IM-related literature details dissolution and/or pharmacokinetic (PK) studies, using methods with limited assessments post-injection events that can impact drug fate, and absorption parameters. Food Drug Association guidelines no longer require preclinical

Язык: Английский

---

Multiphysics Simulation of Liposome Release from Hydrogels for Cavity Filling Following Patient-Specific Breast Tumor Surgery

European Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер unknown, С. 106966 - 106966

Опубликована: Ноя. 1, 2024

Язык: Английский

---

Pharmacokinetics of nano- and microcrystal formulations of low solubility compounds after intramuscular injection to mice

Journal of Pharmacy and Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 14, 2024

The aim of this study was to investigate the pharmacokinetics (PK) poorly soluble compounds when administered intramuscularly (i.m.) as crystalline particles different sizes.

Язык: Английский

---