Toxicokinetic and toxicodynamic considerations in drug research

Rajpoot, Kuldeep; Katare, Pratik; Tekade, Muktika; Sharma, Mukesh C.; Polaka, Suryanarayana; Sengupta, Pinaki; Tekade, Rakesh K.

doi:10.1016/b978-0-323-98367-9.00026-3

Cited by 3 publications

(2 citation statements)

References 89 publications

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“…When these NPs are instilled intranasally, there is a significant increase in the levels of malonaldehyde (MDA), superoxide dismutase, and H 2 O 2 following a timedependent decrease in the glutathione (GSH) levels. 68 5.1.3. Inflammatory Reactions.…”

Section: Toxicological Effects Caused Due Tomentioning

confidence: 99%

“…A few examples of NPs which cause toxicity by this mechanism are Cu NPs, Fe 3 O 4 NPs, and ZnO NPs. When these NPs are instilled intranasally, there is a significant increase in the levels of malonaldehyde (MDA), superoxide dismutase, and H 2 O 2 following a time-dependent decrease in the glutathione (GSH) levels …”

Section: Toxicological Effects Caused Due To Novel Nasal Formulationsmentioning

confidence: 99%

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Nasal Drug Delivery System and Devices: An Overview on Health Effects

Katare,

Pawar Medhe,

Nadkarni

et al. 2024

ACS Chem. Health Saf.

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For centuries, intranasal administration has been a perennial fascination for humanity. In recent times, the realm of nanotechnology-based biomaterials has witnessed a notable resurgence. At its epicenter is the concept of "nose-to-brain" delivery, a pivotal strategy within the pharmaceutical landscape aimed at circumventing the challenges of first-pass metabolism and the reticular endothelium system. This innovative approach spans a spectrum of domains, encompassing drug delivery, diagnostics, theranostics, photothermal and photodynamic therapies, bioengineering, and biomedical engineering. To overcome its multifaceted challenges, the pioneering development of novel formulations is paramount, utilizing the potential of mucoadhesive polymers, sol− gel techniques, pH-dependent absorption, and advanced methodologies. The evolution of excipient technologies has, however, raised concerns surrounding nasal irritation, rapid drainage, and systemic toxicity, affecting both established and emerging formulations. Furthermore, the growing interest in comprehending, evaluating, and documenting the toxicity profiles of nanomaterials stems from their vast range of applications across industries. It sheds light on the various toxicological implications arising from the myriad variables in dosage form formulations, including the role of excipients. It is crucial to note that the mishandling of devices designed for nasal formulation administration can significantly contribute to toxicity concerns. Given these notable developments, this comprehensive review aims to provide an exhaustive examination of current knowledge regarding the physiological consequences of intranasal drug delivery systems within the human body.

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Section: Toxicological Effects Caused Due Tomentioning

confidence: 99%

Section: Toxicological Effects Caused Due To Novel Nasal Formulationsmentioning

confidence: 99%

Nasal Drug Delivery System and Devices: An Overview on Health Effects

Katare,

Pawar Medhe,

Nadkarni

et al. 2024

ACS Chem. Health Saf.

Self Cite

View full text Add to dashboard Cite

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In SilicoToxicity Assessment of Organophosphates: A DFT and Molecular Docking Study on Their Interaction with Human Serum Albumin (HSA)

Singh,

Shankhwar,

Sharma

et al. 2024

Preprint

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This study presents anin silicoanalysis of the toxicity of Organophosphates (OPs) through their interaction with Human Serum Albumin (HSA) protein using density functional theory (DFT) and molecular docking approaches. Organophosphates, known for their widespread use as pesticides, have raised significant concerns due to their potential toxicological effects. To investigate the molecular mechanisms underlying OP toxicity, we conducted DFT calculations to determine the electronic properties and reactivity of selective OP compounds. Molecular docking simulations were performed to explore the binding affinity, interaction sites, and conformational changes of HSA upon exposure to OPs. The DFT analysis revealed key electronic descriptors, such as HOMO-LUMO gap and electrostatic potential, that indicate high reactivity of OPs with biological molecules. Docking results showed strong binding affinities between OPs and HSA, particularly at sites involved in metabolite and drug transport, suggesting potential interference with the protein’s native function. The interaction of OPs with HSA was further supported by molecular dynamics simulations, which confirmed the stability of the OP-HSA complex over time. These findings provide critical insights into the molecular basis of organophosphate toxicity, emphasizing the importance of their interaction with HSA. The combined DFT and molecular docking approach offers a valuable framework for predicting the toxicological behavior of OPs and lays the foundation for furtherin vitroandin vivostudies.Graphical Abstract

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Computational Toxicological Approaches for Drug Profiling and Development of Online Clinical Repositories

Afreen,

Bano

2023

Computational Toxicology for Drug Safety and a Sustainable Environment

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One of the chief reasons for drug attrition and failure to become a marketed drug is the potential toxicity associated with its administration. Therefore, many drugs encountered in the past reached the last phase of drug development successfully but could not be marketed despite their potential drug-likeness due to their inevitable toxicity properties. This issue can be addressed considerably by employing computational toxicological approaches for predicting the toxicity parameters of a drug candidate before its practical synthesis. Pharmaceutical companies utilise computer-based toxicity predictions at the design stage for identifying lead compounds possessing the least toxic properties, and also at the optimization stage for selecting candidates as potential drugs. This integrative field has been exploited for various applications including hazard and risk prioritization of chemicals and safety screening of drug metabolites. The importance of QSTR models for the computational prediction of toxicity is also discussed in this chapter. Various important and predominant software for in silico toxicity prediction including ADMETox, OSIRIS Property Explorer, TopKat and admetSAR 2.0 are also covered herein. This chapter also discusses various freely accessible online clinical repositories such as BindingDB, PubChem, ChEMBL, DrugBank and ChemNavigator iResearch Library. Therefore, the present chapter focuses on the role played by computational toxicology in the procedure of drug profiling and in establishing freely accessible online clinical repositories.

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Toxicokinetic and toxicodynamic considerations in drug research

Cited by 3 publications

References 89 publications

Nasal Drug Delivery System and Devices: An Overview on Health Effects

Nasal Drug Delivery System and Devices: An Overview on Health Effects

In SilicoToxicity Assessment of Organophosphates: A DFT and Molecular Docking Study on Their Interaction with Human Serum Albumin (HSA)

Computational Toxicological Approaches for Drug Profiling and Development of Online Clinical Repositories

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