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Albumin in health and illness conditions. (1) Synthesis of albumin stimulated by hormones and nutrients. (2) Transport of albumin in the circulatory system. (3) Albumin is naturally recycled and returned to the vascular space by the lymphatic system. (4) Important physiological properties of albumin. (5) Albumin crosses the vascular endothelium by transcytosis due to its binding to sialoglycoprotein (gp60) and facilitates drug delivery to tumor microenvironment
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Albumin is an abundant protein in nature with several biological functions. In the human body, both in health and in illness, its transport function is highlighted by the binding to medicinal drugs and consequent distribution in the bloodstream to the site of action. This is particularly relevant for anticancer treatments, since this protein accumu...
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... Albumin in composition of NSPs can also be considered a targeting agent due to the fact that Glycoproteins (Gp18, Gp30, and Gp60) receptor and albumin-binding glycoprotein [secreted protein acidic and rich in cysteine (SPARC)] receptor secreted on the surface of tumor cells can promote preferential uptake of albumin [29,30] and albumin nanoparticles [31]. SPARC as a major modulator of extracellular matrix proliferation and cell migration was showed to be associated with increased tumor invasion and metastasis in various tumor types [30]. ...
Folic acid (FA) residue is a well-known and widely spread targeting ligand, or biovector, used as a component in engineering artificial nanosized and submicron particles (NSPs) to target various cells and treat a variety of diseases that are associated with FA (or folate) receptors (FR) overexpression. A particular place in the list of these diseases is held by various cancer types, for which overexpression of FR on the cell surface is often accompanied by a more severe disease course, increased resistance to the conventional chemotherapy, and poorer prognosis. The incorporation of albumin into NSPs has been shown to enhance their biocompatibility, give high compatibility with drug molecules, prolong their circulation, reduce thrombogenic activity, and improve their colloidal stability. Nowadays albumin-based NSPs with FA residue as a targeting agent are used for chemotherapy, photothermal and photodynamic therapy, combined therapy, visualization, and theranostics (also known as theragnostics) for various types of cancer: breast, cervical, ovarian, prostate, nasopharyngeal, gastric, colorectal, liver cancer, and brain tumors. A limited number of studies have also focused on the use of NSPs in rheumatoid arthritis treatment. In this review, we discuss the ways of FA-albumin conjugation and conjugation of FA to albumin-modified NSPs systems. An application of nanosized and submicron delivery systems on the base of serum albumin and FA for therapy and diagnostics is discussed.
... and it plays a crucial role in drug binding and transportation. Albumin serves several biological functions, but the transportation of ligands around the organism is perhaps the most obvious and should always be considered when designing new therapeutic molecules [25][26][27][28][29][30][31][32][33][34][35][36]. ...
In this study, we employ spectroscopic, thermodynamic and molecular docking approaches to identify the mechanism by which thiazolidinone derivatives 4a – 4d bind with human serum albumin. It has been suggested that the affinity of the interaction of derivatives 4a – 4d with HSA is within the optimal range necessary for the transportation and distribution of compounds within the organism. The binding constant values for the derivative/HSA complexes were found to be 0.03–5.87 × 10 ⁵ M ⁻¹ . Both Δ H ⁰ and Δ S ⁰ values were negative, which indicates that binding occurs mainly through van der Waals forces and hydrogen bonding. The negative values calculated for Δ G ⁰ indicate that the binding of derivatives 4a – 4d with HSA is a spontaneous process. Our study also reveals that derivatives 4a – 4d bind to the subdomain IB (Site III) of HSA and that this binding alters the conformation and thermodynamic stability of HSA. Molecular docking simulations suggest that the main binding forces are van der Waals interactions, hydrophobic interactions and hydrogen bonds. The studied compounds showed weak DPPH‐scavenging activity at all of the tested concentrations. The results suggest that compound 4b with a phenyl substituent at the nitrogen atom of the 1,3‐thiazolidin‐4‐one moiety can be considered the most potent antioxidant in the series.
... HSA is also responsible for binding and transporting different substances, including anticancer drugs. HSA transport function stands out due to the supply of medicine to specific sites through the bloodstream [25,63,79,80]. Therefore, HSA is used in assays to determine the binding mode as a transport agent for new compounds, which aims to determine the biological properties of drug candidates [79]. ...
... HSA transport function stands out due to the supply of medicine to specific sites through the bloodstream [25,63,79,80]. Therefore, HSA is used in assays to determine the binding mode as a transport agent for new compounds, which aims to determine the biological properties of drug candidates [79]. The results obtained by the present investigation show that the free form of HSA obtained maximum fluorescence emission at 329 nm, an intrinsic phenomenon due to the presence of aromatic tryptophan amino acids (Trp), tyrosine (Tyr) and phenylalanine (Phen). ...
... In the presence of increasing quantities of derivatives (Table 5), it was verified that derivatives caused a decrease in HSA fluorescence, which suggest the formation of a HSA compound complex with changes in the microenvironment of the residue Trp-214 [79,83]. Derivative CAPA obtained the highest hypochromic effect with a total decrease of hypochromic effects in ascending order as follows: CAAC < CAIC < CAQA < CAPA. ...
... Albumin adalah protein globular yang larut dalam pelarut air, garam dan asam (Asikin dan Kusumaningrum, 2018). Albumin terdiri dari rantai polipeptida tunggal dari 585 residu asam amino dan memiliki berat molekul sekitar 66 kDa (Ribeiro et al., 2021). Albumin berperan penting dalam peredaran dan farmakodinamik obat antikanker (He et al., 2017), sangat baik digunakan untuk penderita hipoalbumin (rendah albumin), dan penyembuhan luka pasca operasi dan luka bakar (Fitriyani dan Deviarni, 2016), serta mempertahankan onkotik intravaskuler (koloid osmotik), memudahkan pergerakan cairan tubuh, dan memudahkan pemindahan zat (Nugroho et al., 2021 bahan inti dan bahan pelapis, tahap enkapsulasi, sifat dan struktur dinding mikrokapsul serta kondisi pembentukan mikrokapsul (Mahlani, 2016). ...
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... Drugs are transported in the circulation either in a free form, dissolved in the aqueous phase of plasma, or complexed with plasma proteins in varying degrees [1,2]. This drug-protein binding is reversible in nature, and an equilibrium between the bound and free drug molecules exists [3,4]. Serum albumin is the most abundant circulatory protein in blood plasma and plays an important role in the transport and deportation of different types of endogenous and exogenous compounds to target cells [5,6]. ...
Pictilisib (GDC-0941) is a well-known dual inhibitor of class I PI3K and mTOR and is presently undergoing phase 2 clinical trials for cancer treatment. The present work investigated the dynamic behaviors and interaction mechanism between GDC-0941 and human serum albumin (HSA). Molecular docking and MD trajectory analyses revealed that GDC-0941 bound to HSA and that the binding site was positioned in subdomain IIA at Sudlow’s site I of HSA. The fluorescence intensity of HSA was strongly quenched by GDC-0941, and results showed that the HSA–GDC-0941 interaction was a static process caused by ground-state complex formation. The association constant of the HSA–GDC-0941 complex was approximately 10⁵ M⁻¹, reflecting moderate affinity. Thermodynamic analysis conclusions were identical with MD simulation results, which revealed that van der Waals interactions were the vital forces involved in the binding process. CD, synchronous, and 3D fluorescence spectroscopic results revealed that GDC-0941 induced the structural change in HSA. Moreover, the conformational change of HSA affected its molecular sizes, as evidenced by AFM. This work provides a useful research strategy for exploring the interaction of GDC-0941 with HSA, thus helping in the understanding of the transport and delivery of dual inhibitors in the blood circulation system.
... Albumin adalah protein globular yang larut dalam pelarut air, garam dan asam (Asikin dan Kusumaningrum, 2018). Albumin terdiri dari rantai polipeptida tunggal dari 585 residu asam amino dan memiliki berat molekul sekitar 66 kDa (Ribeiro et al., 2021). Albumin berperan penting dalam peredaran dan farmakodinamik obat antikanker (He et al., 2017), sangat baik digunakan untuk penderita hipoalbumin (rendah albumin), dan penyembuhan luka pasca operasi dan luka bakar (Fitriyani dan Deviarni, 2016), serta mempertahankan onkotik intravaskuler (koloid osmotik), memudahkan pergerakan cairan tubuh, dan memudahkan pemindahan zat (Nugroho et al., 2021). ...
Albumin diketahui memiliki banyak manfaat bagi kesehatan. Albumin merupakan protein globular yang larut dalam pelarut air, garam dan asam. Struktur albumin secara umum terdiri dari rantai polipeptida tunggal dari 585 residu asam amino dan memiliki berat molekul sekitar 66 kDa. Albumin memiliki karakteristik sensitif terhadap pH (terlalu asam atau terlalu basa) serta suhu yang ekstrim yang dapat menyebabkan pembengkakan struktur, denaturasi, maupun pengendapan protein. Salah satu metode yang menjanjikan untuk melindungi senyawa bioaktif sehingga lebih stabil dan dapat menghindari reaksi yang tidak diinginkan adalah dengan enkapsulasi. Enkapsulasi merupakan proses perlindungan atau pelapisan suatu bahan aktif oleh bahan lain atau suatu sistem matriks. Zat yang dienkapsulasi disebut sebagai inti sedangkan substansi yang mengenkapsulasi sering disebut pelapis. Keberhasilan dari proses enkapsulasi dipengaruhi oleh beberapa faktor seperti sifat fisiko kimia bahan inti dan bahan pelapis, tahap enkapsulasi, sifat dan struktur dinding mikrokapsul serta kondisi pembentukan mikrokapsul. Dalam tulisan ini dibahas beberapa metode enkapsulasi yang dapat digunakan untuk albumin dan riset enkapsulasi albumin yang telah dilakukan.
Thiosemicarbazones and thiazoles are known for their diverse biological activities. This study introduced two series of molecules, 4-(3-(4-nitrophenyl)-4-phenylthiazol-2(3H)-ylidene)-hydrazine)-methyl)-phenol and 4-(3-(4-chlorophenyl)-4-phenylthiazol-2(3H)-ylidene)-hydrazine)-methyl)-phenol, which exhibit biological potential as antioxidant agents. The study also assessed the interaction of these compounds with various HSA/DNA macromolecules. The results of the antioxidant activity showed that thiazoles in the DPPH assay exhibited IC50 values ranging from 439.4 to 691.67 µM. In the ABTS assay, thiosemicarbazones exhibited significant activity, ranging from 39.19 to 50.03 µM. Interaction assays were carried out with human serum albumin (HSA) and DNA. All compounds were able to interact with both DNA (low to moderate interaction) and HSA (moderate to high interaction).
