To investigate the effect of functional groups in bovine serum albumin (BSA) on its tissue distribution characteristics, tyrosine (Tyr) or tryptophan (Trp) residues of BSA were chemically modified by tetranitromethane (TNM) and 2-hydroxy-5-nitrobenzyl bromide (HNB), respectively. BSA was successfully modified with each reagent depending on the amount of the reagent added to the reaction mixture, and TNM- and HNB-modified BSA derivatives with different degrees of modification were obtained. Circular dichroism measurements showed that slight secondary and large tertiary changes were detectable as the degree of modification increased. After intravenous injection into mice, all synthetic BSA derivatives were eliminated very slowly from the systemic circulation. However, (111)In-TNM(6.6)- and (111)In-HNB(2.0)-BSA, derivatives with a high degree of modification, showed a slightly faster disappearance from the systemic circulation and slightly higher accumulation in the liver than (111)In-unmodified BSA. Pharmacokinetic analyses also demonstrated that the modification of Tyr or Trp residues on BSA had only marginal effects on tissue distribution. These results indicate that the Tyr and Trp residues have little effect on the tissue distribution characteristics of serum albumins, and that the specific modification of these residues may be a promising approach to designing sustained drug delivery systems using serum albumins.
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http://dx.doi.org/10.1248/bpb.29.1926 | DOI Listing |
Clin Cancer Res
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Bristol-Myers Squibb (United States), Summit, New Jersey, United States.
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Anhui Provincial Center of Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, People's Republic of China.
Topiramate is an antiepileptic drug (AED) that is effective in treating various types of epilepsy. This study evaluated the bioequivalence and safety of two topiramate tablets in healthy Chinese subjects under fasting and fed conditions. We designed an open-label, randomized, single-dose, two-period, crossover trial protocol.
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Certara, Canterbury, UK.
The application of quantitative systems pharmacology (QSP) has enabled substantial progress and impact in many areas of therapeutic discovery and development. This new technology is increasingly accepted by industry, academia, and solution providers, and is enjoying greater interest from regulators. In this chapter, we summarize key aspects regarding how effective collaboration among institutions and disciplines can support the growth of QSP and expand its application domain.
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Organic fluorescence and colorimetric probes have emerged as vital tools for detecting metal ions, due to their high sensitivity, selectivity, and rapid response times. Copper, an essential trace element, plays a critical role in biological systems, yet its imbalance can lead to severe disorders such as neurodegenerative diseases, cancer, and Wilson's disease. Over the past few years, advancements in probe design have unlocked innovative avenues for not only detecting Cu in environmental and biological samples but also for visualizing its distribution through fluorescence imaging.
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