A molecular dynamics study on the binding of gemcitabine to human serum albumin

Kharazian, Bahar; Ahmad, Ashfaq; Mabudi, A.

doi:10.1016/j.molliq.2021.116496

Cited by 11 publications

(9 citation statements)

References 69 publications

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“…The in situ HTA self-assembly (Figure A) process employed in this study is capable of encapsulating dual drugs in their cross-linked networks. , HSA is capable of binding GA − and Gem. ,, It is anticipated that both GA and Gem are bound to HSA protein chains and uniformly dispersed in the HSA matrix. This HSA–drug matrix is stabilized by tannic acid (TA).…”

Section: Resultsmentioning

confidence: 99%

“…31 HSA is an excellent platform for drug delivery as it is equipped with hydrophobic and hydrophilic domains which provide a dual loading capacity. 29,30 HSA can efficiently bind to GA 43−45 and Gem 34,46,47 and form self-assemblies. Upon binding, both GA and Gem are uniformly dispersed in the HSA matrix.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, there are about 11 different HSA-based medical formulations that are being used in clinics for the treatment of cancer (Abraxane and Pegintron), emphysema (Aralast NPs), infections (Pegintron), multiple sclerosis (Avonex), blood clots (Urokinase), maintenance of blood volume/cardiac or pulmonary functions (Alburex, Jeanatope, and Megatope), detection of cancers or contrast agent (Nanocoll and Optison), and diabetes (Albiglutide) . HSA is an excellent platform for drug delivery as it is equipped with hydrophobic and hydrophilic domains which provide a dual loading capacity. , HSA can efficiently bind to GA − and Gem ,, and form self-assemblies. Upon binding, both GA and Gem are uniformly dispersed in the HSA matrix.…”

Section: Discussionmentioning

confidence: 99%

“…41,42 HSA is capable of binding GA 43−45 and Gem. 34,46,47 It is anticipated that both GA and Gem are bound to HSA protein chains and uniformly dispersed in the HSA matrix. This HSA−drug matrix is stabilized by tannic acid (TA).…”

Section: Synthesis and Characterization Of G−g@htamentioning

confidence: 94%

See 3 more Smart Citations

In Situ Nanoparticle Self-Assembly for Combination Delivery of Therapeutics to Non-Small Cell Lung Cancer

Nagesh

Chauhan

Jaggi

et al. 2022

ACS Appl. Bio Mater.

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Chemotherapy often experiences several challenges including severe systemic toxicity and adverse effects. The combination chemotherapy arose as an effective clinical practice aimed at reducing doses of drugs to achieve synergistic actions with low toxicity. Our recent efforts demonstrated a synergistic therapeutic benefit of gambogic acid (GA) and gemcitabine (Gem) against lung cancer. However, simultaneous delivery of these two drugs at the tumor site is highly challenging. Therefore, the development of an injectable formulation that can effectively deliver both hydrophobic (GA) and hydrophilic (Gem) drugs in one formulation is a clinically unmet need. Herein, this study reports an in situ human serum albumin (HSA)-and tannic acid (TA)-mediated complexed GA and Gem nanoparticles (G−G@HTA NPs). G−G@HTA NP formation was confirmed by the particle size, Fourier transform infrared spectroscopy, and 1 H NMR spectroscopy. The superior therapeutic activity of G−G@HTA NPs was demonstrated by multiple in vitro functional assays. Additionally, G−G@HTA NPs revealed an obvious and precise targeting of tumors in vivo. The promoted and more synergistic anti-tumor efficacy of G−G@HTA NPs was attained than that of combined treatments and single drug treatments. These events have resulted in no apparent systemic and organ toxicities. Together, this study suggests that in situ HSA− TA-based combinatorial treatment strategy is a suitable approach for application in lung cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Synthesis and Characterization Of G−g@htamentioning

confidence: 94%

See 2 more Smart Citations

In Situ Nanoparticle Self-Assembly for Combination Delivery of Therapeutics to Non-Small Cell Lung Cancer

Nagesh

Chauhan

Jaggi

et al. 2022

ACS Appl. Bio Mater.

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“…Molecules 2022, 27, x 3 of 21 addition, molecular docking is an important method in computer-aided drug design due to its uncomplicated operations and commands that allows users to get results instantly as compared to other computational methods [40]. Although, in a recent study, the binding of gemcitabine with HSA was seen using 10 ns molecular dynamics simulation [41], but this study was designed to see the stability of the drug-HSA complex when the drug was bounded to site 1 and site 2. In the present study, we have seen the detailed binding of HSA with gemcitabine along with the effect of ibuprofen on the binding using experimental, as well as computational, methods.…”

Section: Uv-visible Absorption Studiesmentioning

confidence: 99%

Experimental and Computational Investigation on the Interaction of Anticancer Drug Gemcitabine with Human Plasma Protein: Effect of Copresence of Ibuprofen on the Binding

Ali

Al‐Lohedan

2022

Molecules

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The interaction of common anticancer drug gemcitabine with human serum albumin (HSA) has been studied in detail. The effect of an omnipresent nonsteroidal anti-inflammatory drug ibuprofen was also seen on the binding of HSA and gemcitabine. A slight hyperchromic shift in the difference UV-visible absorption spectra of HSA on the addition of gemcitabine gave a primary idea of the possible complex formation between them. The inner filter effect, which happens due to the significant absorbance of the ligand at the excitation and/or emission wavelengths, played an important role in the observed fluorescence quenching of HSA by gemcitabine that can be understood by comparing the observed and corrected fluorescence intensities obtained at λex = 280 nm and 295 nm. Gemcitabine showed weak interaction with HSA, which took place via a dynamic quenching mechanism with 1:1 cooperative binding between them. Secondary structural analysis, based on circular dichroism (CD) spectroscopy, showed that low concentrations of gemcitabine did not affect the native structure of protein; however, higher concentrations affected it slightly with partial unfolding. For understanding the binding site of gemcitabine within HSA, both experimental (using site markers, warfarin and ibuprofen) as well as computational methods were employed, which revealed that the gemcitabine binding site is located between the interface of subdomain IIA and IIB within the close proximity of the warfarin site (drug site 1). The effect of ibuprofen on the binding was further elaborated because of the possibility of its coexistence with gemcitabine in the prescription given to the cancer patients, and it was noticed that, ibuprofen, even present in high amounts, did not affect the binding efficacy of gemcitabine with HSA. DFT analyses of various conformers of gemcitabine obtained from its docking with various structures of HSA (free and bounded with site markers), show that the stability of the gemcitabine molecule increased slightly after binding with ibuprofen-complexed HSA. Both experimental as well as computational results were in good agreement with each other.

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Nirmatrelvir, A COVID‐19 Drug, and Human Serum Albumin: Computational Analysis of Their Molecular Interactions

Abubakar,

Bin Mohamad,

Zaroog

et al. 2024

ChemistrySelect

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Understanding the interaction between drugs and human serum albumin (HSA) is crucial for drug development. This study investigates the binding of a COVID‐19 drug, nirmatrelvir (NIR), to HSA through a computational approach. Molecular docking was employed to identify potential NIR binding site on HSA, and revealed distinct clusters at Sites I, II, and III. However, Site III exhibited a preference for NIR based on the lowest binding energy. Molecular dynamics simulation over 100 ns confirmed the stability of the NIR−HSA complex, with consistent binding at Site III. The compactness of HSA was maintained throughout the simulation period, as indicated by the radius of gyration, while structural flexibility analysis revealed typical fluctuations around some residues. Root‐mean‐square deviation (RMSD) patterns illustrated stability of the complex, and hydrogen bond analysis suggested four stable hydrogen bonds between NIR and HSA. These investigations offer insightful information on molecular interactions governing the stability of the NIR−HSA complex.

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A molecular dynamics study on the binding of gemcitabine to human serum albumin

Cited by 11 publications

References 69 publications

In Situ Nanoparticle Self-Assembly for Combination Delivery of Therapeutics to Non-Small Cell Lung Cancer

In Situ Nanoparticle Self-Assembly for Combination Delivery of Therapeutics to Non-Small Cell Lung Cancer

Experimental and Computational Investigation on the Interaction of Anticancer Drug Gemcitabine with Human Plasma Protein: Effect of Copresence of Ibuprofen on the Binding

Nirmatrelvir, A COVID‐19 Drug, and Human Serum Albumin: Computational Analysis of Their Molecular Interactions

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