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Toxicity and Cellular Uptake of Gold Nanoparticles: What We Have Learned So Far *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Alaaldin M. Alkilany, Catherine J. Murphy
Drug pharmacokinetics is the sum of vital processes including drug absorption, distribution, metabolism, and elimination. Before any drug obtains regulatory approval, its pharmacokinetic parameters should be determined. Similar to pharmaceutical drugs, studying the pharmacokinetics of nanoparticles in vivo to assess their absorption, biodistribution, metabolism, elimination processes is essential (Chen et al. 2009). The biodistribution of gold nanoparticles into different tissues can be studied by isolation of the targeted organ, followed by acid digestion to oxidize and extract the gold ions, which can be then quantified by ICP-MS. The same concept can be employed to study the blood and renal clearance of gold nanoparticles by analyzing the gold content in the blood or urine samples as a function of time. After obtaining the required information about the level of gold nanoparticles in different compartments (blood and urine) as function of time, classical pharmacokinetics models can be applied to obtain important pharmacokinetic parameters such as volume of distribution (Vd), maximum plasma concentration (Cmax), blood half time (t1/2), total body clearance (Cl), etc. (Cho et al. 2009b).
Drug Design, Synthesis, and Development
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Drug distribution is the next step in the pharmacokinetics of a drug. Once the drug has diffused into the capillaries, it is speedily distributed around the blood stream, and then more slowly distributed to various tissues and organs. Drug molecules do not have to cross cell membranes in order to leave the blood system and enter tissues. Capillaries contain small pores between cells through which drug-sized molecules can pass, but not important plasma proteins. If the drug target is an extracellular receptor, the drug can find the target, bind to it, and perform its function. Drugs that have targets within the cell, such as enzyme inhibiters, or drugs acting on nucleic acids, must leave the extracellular aqueous fluid and traverse cell membranes to access their targets. To do this, the drug must be sufficiently hydrophobic, or be able to utilise carrier proteins, or be taken in by pinocytosis. If a drug is excessively hydrophobic, it can become absorbed into fatty tissue, thus lowering the concentration available to bind to the target. Likewise, drugs that are ionised may be less available in the blood supply if they become bound to macromolecules; for example they can become irreversibly bound to blood plasma proteins.
Vitamin C Pharmacokinetics *
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Pharmacokinetics comprises the descriptions of absorption, distribution, metabolism, and excretion of drugs. The use of pharmacokinetics to describe these processes is based on various mathematical models, all of which have a set of assumptions that needs to be fulfilled for their validity. In Table 4.1, vitamin C is compared to a typical orally administered low molecular weight drug with respect to general pharmacokinetic properties [26]. As can be deduced from the table, there are more differences than similarities between vitamin C and the typical pharmaceutical drug when it comes to pharmacokinetics. Unfortunately, lack of appropriate attention to the unusual behavior of vitamin C has hampered the proper evaluation of its therapeutic potential in the majority of the clinical literature as reviewed elsewhere [11,26,27]. In the following, these similarities and differences are explored in more detail.
Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs
Published in Drug Metabolism Reviews, 2023
Amina Džidić-Krivić, Jasna Kusturica, Emina Karahmet Sher, Nejra Selak, Nejra Osmančević, Esma Karahmet Farhat, Farooq Sher
Many studies have been conducted in the last two decades attempting to prove the interplay between gut microbiota and drug pharmacokinetics as shown in Table 1. Four basic processes researched in the area of pharmacokinetics are drug absorption, their distribution in the organism followed by drug metabolism. The final step is drug elimination or excretion. This dialogue between four complex pharmacokinetic processes has an important role in the successful clinical outcome after the treatment with the observed drug in the organism as well as in the occurrence of drug potential side effects. As it is known, the same drug can show positive and toxicological effects. The most important differing factor is the used dosage that is highly influenced by the dynamic of basic pharmacokinetic processes (Chen et al. 2021).
Impact of DNA methylation on ADME gene expression, drug disposition, and efficacy
Published in Drug Metabolism Reviews, 2022
Xu Hao, Yuanyuan Li, Jialu Bian, Ying Zhang, Shiyu He, Feng Yu, Yufei Feng, Lin Huang
The pharmacokinetic process includes the absorption, distribution, metabolism, and excretion (ADME) of drugs in organisms. The expression of ADME genes such as transporters, phase I metabolic enzymes, phase II metabolic enzymes, and nuclear receptors affect the effectiveness and safety of drugs via intervening in drug disposal. It is well known that the expression of drug-metabolizing enzymes and transporters is affected by genetic polymorphism and nuclear receptors (Johansson and Ingelman-Sundberg 2011; Sissung et al. 2012; Xu et al. 2018), which can only explain some of the interindividual differences in clinical treatment (Bonder et al. 2014; Xu et al. 2018). Kacevska et al. suggested that the ADME genes undergo epigenetic regulation (Kacevska et al. 2011). Epigenetics is not the study of the effects of DNA sequence changes on gene expression. Epigenetic regulation leads to relatively stable changes, which are usually affected by age, diet, lifestyle, disease, and environment (Peng and Zhong 2015). The mechanisms of epigenetic regulation of ADME gene expression include DNA methylation, histone modification and non-coding RNAs (Hirota et al. 2017).
Why do few drug delivery systems to combat neglected tropical diseases reach the market? An analysis from the technology’s stages
Published in Expert Opinion on Therapeutic Patents, 2022
Jabson Herber Profiro de Oliveira, Igor Eduardo Silva Arruda, José Izak Ribeiro de Araújo, Luise Lopes Chaves, Mônica Felts de La Rocca Soares, José Lamartine Soares-Sobrinho
The patents for the main drugs used to combat NTDs have expired. However, the development of new pharmaceutical forms and technologies for the delivery of these drugs is subject to new patents. The risk involved in the development of new dosage forms available on the market is considerably lower than the development of new drugs, as the main objective is to improve specific pharmacokinetic characteristics [300]. In this sense, different materials with well-defined specific properties can be used. One of the strategies used in the development of new pharmaceutical forms is the adjustment of drug delivery by more adequate routes of administration (to increase bioavailability) or more comfortable for the patient. In turn, absorption is one of the main steps in pharmacokinetics, in this step it is essential to consider parameters such as: (1) characteristics of the pharmaceutical preparation and formulation (2) physicochemical property of the molecule (3) factors inherent to the absorption site and (4) first pass metabolism [301].