Human serum albumin-based design of a diflunisal prodrug

Yang, Feng; Yuan, Zhi; Zhang, Yao; Li, Guo Qing; Li, Mei; Qin, Jiang Ke; Lockridge, Oksana; Liang, Hong

doi:10.1016/j.ejpb.2013.01.013

Cited by 21 publications

(16 citation statements)

References 28 publications

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“…HSA has three main binding sites for various kinds of endogenous and exogenous compounds: site 1 in the IIA sub-domain, site 2 in the IIIA sub-domain, and site 3 in the IB sub-domain (Zsila, 2013 ). Among the three binding sites, the endogenous non-esterified fatty acids (FA) occupy site 2 or displace drugs to bind to site 2 in vivo because site 2 is the strongest binding site of FA (Simard et al., 2005 , 2006 ; Yang et al., 2013 ). Thus, reasonable consideration of the nature of drugs has resulted in our development of HSA multi-drug delivery systems in which two agents, respectively, bind to the IB and IIA sub-domains of HSA while the third drug is conjugated to HSA ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

HSA-based multi-target combination therapy: regulating drugs’ release from HSA and overcoming single drug resistance in a breast cancer model

Gou

Zhang

et al. 2018

Drug Delivery

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Multi-drug delivery systems, which may be promising solution to overcome obstacles, have limited the clinical success of multi-drug combination therapies to treat cancer. To this end, we used three different anticancer agents, Cu(BpT)Br, NAMI-A, and doxorubicin (DOX), to build human serum albumin (HSA)-based multi-drug delivery systems in a breast cancer model to investigate the therapeutic efficacy of overcoming single drug (DOX) resistance to cancer cells in vivo, and to regulate the drugs’ release from HSA. The HSA complex structure revealed that NAMI-A and Cu(BpT)Br bind to the IB and IIA sub-domain of HSA by N-donor residue replacing a leaving group and coordinating to their metal centers, respectively. The MALDI-TOF mass spectra demonstrated that one DOX molecule is conjugated with lysine of HSA by a pH-sensitive linker. Furthermore, the release behavior of three agents form HSA can be regulated at different pH levels. Importantly, in vivo results revealed that the HSA–NAMI-A–Cu(BpT)Br–DOX complex not only increases the targeting ability compared with a combination of the three agents (the NAMI-A/Cu(BpT)Br/DOX mixture), but it also overcomes DOX resistance to drug-resistant breast cancer cell lines.

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Section: Discussionmentioning

confidence: 99%

HSA-based multi-target combination therapy: regulating drugs’ release from HSA and overcoming single drug resistance in a breast cancer model

Gou

Zhang

et al. 2018

Drug Delivery

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“…Therefore, in order to optimize the reasonable binding affinity of this drug molecule to albumin protein, rather than to use drug molecule itself, Liang etc proposed a new diflunisal-HSA complex by incorporation of diflunisal prodrug into HSA. This prodrug-HSA complex displayed a relative weak intramolecular interaction than the complex formed by diflunisal and HSA [44]. The reduced binding affinity of prodrug to HSA holds great advantages in effective release of prodrugs from albumin carrier into the circulation, which thus significantly improved the drug bioavailability.…”

Section: [Reprinted By Copyright Permission Of American Chemical Socimentioning

confidence: 98%

“…Generally, the presence of hydrophobic moieties in a drug molecule structure could enhance its affinity to HSA indeed, thus stabilize the drug-HSA protein conjugates for the purpose of improving drug stability and circulation retention. Although, this strategy has been extensively used in the design of anticancer macromolecular drugs, in some cases, HSA binding, if too strong, could also potentially prevent the recognition of drug molecules from the targeted enzymes or proteins, and therefore greatly compromised the treatment efficacy [43,44]. For example, diflunisal, a salicylic acid derivative, has been widely used in the clinics for its anti-inflammatory activity.…”

Section: [Reprinted By Copyright Permission Of American Chemical Socimentioning

confidence: 99%

Recent Advances on the Development of Pharmacotherapeutic Agents on the Basis of Human Serum Albumin

Liu

Mu²,

Xing³

2015

CPD

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Human serum albumin (HSA), a major transport protein component in blood plasma, has been reported recently to play many important roles in pharmacotherapeutics development. Owing to its promising intrinsic binding capability of drug molecules, HSA offers favorable characteristics and can be directly used as its monomeric formula or can be fabricated into protein based nanoparticle platforms to realize the effective delivery of therapeutic molecules into targeted diseases areas. In addition, HSA can also serve as a protein stabilizer or environment-responsive moieties to hybridize with the functional materials including polymers or inorganic nanoparticles through the covalent reactions or electrostatic interactions, and can thus greatly alter the relevant biological distribution and pharmacokinetic behavior to improve their therapeutic efficacy. By right, extensive studies have been conducted to develop HSA-conjugated pharmacotherapeutic agents toward effective in vitro and in vivo diseases diagnosis and treatment. The current review gives an in-detail account of the latest progresses of HSA-based carriers as functional protein materials, mainly with respect to its conjugation types, formulation aspects, and importantly their promising applications towards enhanced drug delivery and medical diagnosis.

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“…The binding affinity of the drug to the carrier exerts an influence on its release rate . Thus, the binding affinity of active compounds to HSA can be regulated by optimizing the drugs or modifying certain amino acids based on the HSA complex structures . Utilizing HSA as a drug delivery system has many beneficial characteristics.…”

Section: Resultsmentioning

confidence: 99%

Binding and Anticancer Properties of Plumbagin with Human Serum Albumin

Gou

Zhang

et al. 2015

Chem Biol Drug Des

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Plumbagin has received extensive attention as a promising anticancer drug. Therefore, we investigated the binding and anticancer properties of plumbagin with human serum albumin. Fluorescence results demonstrated that plumbagin interacts with human serum albumin, although its binding affinity may be affected to various extents by different compounds. The human serum albumin-plumbagin complex structure revealed that plumbagin binds to the hydrophobic cavity in the IIA subdomain of human serum albumin through hydrogen bonding and hydrophobic interactions. The plumbagin-human serum albumin complex enhances cytotoxicity by 2- to 3-fold particularly in cancer cells but has no effect on normal cells in vitro. Compared with the unbound drug, the human serum albumin-plumbagin complex promotes HeLa cell apoptosis and has a stronger capacity for cell cycle arrest at the G2/M phase of HeLa cells. In conclusion, this study contributes to the rational design and development of plumbagin-based drugs and a drug-human serum albumin delivery system.

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Human serum albumin-based design of a diflunisal prodrug

Cited by 21 publications

References 28 publications

HSA-based multi-target combination therapy: regulating drugs’ release from HSA and overcoming single drug resistance in a breast cancer model

HSA-based multi-target combination therapy: regulating drugs’ release from HSA and overcoming single drug resistance in a breast cancer model

Recent Advances on the Development of Pharmacotherapeutic Agents on the Basis of Human Serum Albumin

Binding and Anticancer Properties of Plumbagin with Human Serum Albumin

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