DFT investigation of 5-fluorouracil tautomerism and non-covalent interactions with PLGA nanoparticles for enhanced drug delivery and sensing

被引：0

作者：

Saadh, Mohamed J. ^{[1
]}

Kyada, Ashishkumar ^{[2
]}

Jyothi, S. Renuka ^{[3
]}

Kumar, M. Ravi ^{[4
]}

Allela, Omer Qutaiba B. ^{[5
]}

Nathiya, Deepak ^{[6
]}

Kaur, Parjinder ^{[7
]}

Sead, Fadhil Faez ^{[8
,9
]}

Kaur, Jupinder ^{[10
]}

Ghafouriraz, Shima ^{[11
]}

机构：

[1] Middle East Univ, Fac Pharm, Amman 11831, Jordan

[2] Marwadi Univ, Fac Hlth Sci, Res Ctr, Dept Pharmaceut Sci, Rajkot, Gujarat, India

[3] JAIN Univ, Sch Sci, Dept Biotechnol & Genet, Bangalore, Karnataka, India

[4] Raghu Engn Coll, Dept Chem, Visakhapatnam 531162, Andhra Pradesh, India

[5] Alnoor Univ, Coll Pharm, Nineveh, Iraq

[6] Nims Univ Rajasthan, Nims Inst Pharm, Dept Pharm Practice, Jaipur, India

[7] Chandigarh Grp Coll Jhanjeri, Chandigarh Pharm Coll, Mohali 140307, Punjab, India

[8] Islamic Univ, Coll Dent, Dept Dent, Najaf, Iraq

[9] Islamic Univ Al Diwaniyah, Med Lab Tech Coll, Dept Med Anal, Al Diwaniyah, Iraq

[10] Vishwakarma Inst Technol, Dept Engn Sci, Kondhwa Budruk, Pune 411037, Maharashtra, India

[11] Univ Extremadura, Sch Technol, INTERRA, Caceres 10003, Spain

来源：

SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY | 2025年 / 335卷

关键词：

5-Fluorouracil; PLGA; Drug delivery; Optoelectronic properties; DFT; CANCER; FABRICATION; RELEASE;

D O I：

10.1016/j.saa.2025.125945

中图分类号：

O433 [光谱学];

学科分类号：

0703 ; 070302 ;

摘要：

This study investigates the non-covalent interactions between both the free and tautomeric forms of 5-fluorouracil (5-FU) and poly(lactic-co-glycolic acid) (PLGA) nanoparticles through density functional dispersion correction (DFT-D) at the B3LYP-D level in a dichloromethane (DCM) and water environments. Our results indicate that the non-covalent interactions formed between the carbonyl and amide groups of the free form of 5FU and the carboxyl group of PLGA facilitate a rapid initial release of the drug, aligning with experimental findings. The calculated binding energies for 5-FU in its keto-enol (-0.80 eV) and di-enol forms (-0.74 eV) demonstrate exothermic processes, highlighting the enhanced drug loading capacity of the tautomeric forms compared to the free form (-0.627 eV). NBO analysis indicates a charge transfer of 0.061e in the keto-enol form, compared to 0.053e in the free form. Infrared (IR) spectra show shifts in the N-H and C--O stretching frequencies, suggesting the formation of hydrogen bonds between 5-FU and the carbonyl groups of PLGA. Timedependent DFT calculations revealed significant shifts in the optical properties of 5-FU upon interaction with the PLGA carrier. Adsorption of 5-FU in its most stable configuration resulted in a red shift to 253.56 nm, while the PLGA carrier exhibited a blue shift to 213.08 nm. Analysis of oscillator strengths indicated an increased adsorption intensity for the keto-enol form of 5-FU, suggesting a hypochromic effect. Total density of states (TDOS) analysis demonstrates that 5-FU notably influences the HOMO and LUMO levels, with PLGA nanoparticles exhibiting higher sensitivity (state I: 30.07 %) to 5-FU in one state compared to another (state VII: 28.99 %), likely due to variations in energy gaps. These findings indicate that PLGA nanoparticles possess significant potential as both drug carriers and sensors for 5-FU detection in solvent phases.

引用

页数：12

共 47 条

[1] Exploring curcumin interaction with PLGA nanoparticles via various functional groups: A dispersion-corrected density functional theory and molecular dynamics simulation approach [J].