DFT investigation of therapeutic potential of benzimidazolone capsule as a drug delivery vehicle for anticancer drug

Abstract Numerous issues with pharmacokinetics and water solubility of current anticancer drugs have hindered the development of chemotherapy, resulting in significant side effects and patient resistance to multiple therapies. Nanomedicine revolutionized cancer treatment by introducing nanocarriers...

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Main Authors: Kaynat Akhtar, Sehrish Sarfaraz, Muhammad Yar, Malai Haniti Sheikh Abdul Hamid, Nadeem S. Sheikh, Khurshid Ayub
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-12817-7
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author Kaynat Akhtar
Sehrish Sarfaraz
Muhammad Yar
Malai Haniti Sheikh Abdul Hamid
Nadeem S. Sheikh
Khurshid Ayub
author_facet Kaynat Akhtar
Sehrish Sarfaraz
Muhammad Yar
Malai Haniti Sheikh Abdul Hamid
Nadeem S. Sheikh
Khurshid Ayub
author_sort Kaynat Akhtar
collection DOAJ
description Abstract Numerous issues with pharmacokinetics and water solubility of current anticancer drugs have hindered the development of chemotherapy, resulting in significant side effects and patient resistance to multiple therapies. Nanomedicine revolutionized cancer treatment by introducing nanocarriers to enhance drug delivery. This study investigates the use of benzimidazolone capsules as nanocarrier for drug delivery of flutamide (FLT) and gemcitabine (GB) (FLT@Cap and GB@Cap). Numerous structural and electrical parameters demonstrate that both drugs interact well with nanocapsules and are easily transported to the targeted site. Using complexation energy analysis, quantum theory of atoms in molecules (QTAIM), non-covalent interactions (NCI), natural bond orbital (NBO), frontier molecular orbital (FMO), and density of states (DOS) analyses, the drug delivery of flutamide (FLT) and gemcitabine (GB) via benzimidazolone capsule is described. FLT@Cap and GB@Cap exhibit strong drug-capsule interaction, with adsorption energies of -42.18 and − 51.59 kcal/mol, respectively. QTAIM and NCI analysis validate the non-covalent interactions between FLT, GB, and capsule. To comprehend the shifting of electron density from drug to surface, NBO analysis is utilized. After complexation, (EH−L) which describes the HOMO-LUMO energy gap is reduced, and the perturbations in the electronic parameters are estimated using FMO analysis. The results indicate a high degree of selectivity for FLT and GB on the surface of the benzimidazolone capsule.
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spelling doaj-art-ce40d2783b0b44f68769ec5e954952832025-08-20T04:03:07ZengNature PortfolioScientific Reports2045-23222025-08-0115111610.1038/s41598-025-12817-7DFT investigation of therapeutic potential of benzimidazolone capsule as a drug delivery vehicle for anticancer drugKaynat Akhtar0Sehrish Sarfaraz1Muhammad Yar2Malai Haniti Sheikh Abdul Hamid3Nadeem S. Sheikh4Khurshid Ayub5Department of Chemistry, COMSATS UniversityDepartment of Chemistry, COMSATS UniversityDepartment of Physiology & Biochemistry, Cholistan University of Veterinary and Animal SciencesChemical Sciences, Faculty of Science, Universiti Brunei DarussalamChemical Sciences, Faculty of Science, Universiti Brunei DarussalamDepartment of Chemistry, COMSATS UniversityAbstract Numerous issues with pharmacokinetics and water solubility of current anticancer drugs have hindered the development of chemotherapy, resulting in significant side effects and patient resistance to multiple therapies. Nanomedicine revolutionized cancer treatment by introducing nanocarriers to enhance drug delivery. This study investigates the use of benzimidazolone capsules as nanocarrier for drug delivery of flutamide (FLT) and gemcitabine (GB) (FLT@Cap and GB@Cap). Numerous structural and electrical parameters demonstrate that both drugs interact well with nanocapsules and are easily transported to the targeted site. Using complexation energy analysis, quantum theory of atoms in molecules (QTAIM), non-covalent interactions (NCI), natural bond orbital (NBO), frontier molecular orbital (FMO), and density of states (DOS) analyses, the drug delivery of flutamide (FLT) and gemcitabine (GB) via benzimidazolone capsule is described. FLT@Cap and GB@Cap exhibit strong drug-capsule interaction, with adsorption energies of -42.18 and − 51.59 kcal/mol, respectively. QTAIM and NCI analysis validate the non-covalent interactions between FLT, GB, and capsule. To comprehend the shifting of electron density from drug to surface, NBO analysis is utilized. After complexation, (EH−L) which describes the HOMO-LUMO energy gap is reduced, and the perturbations in the electronic parameters are estimated using FMO analysis. The results indicate a high degree of selectivity for FLT and GB on the surface of the benzimidazolone capsule.https://doi.org/10.1038/s41598-025-12817-7Drug deliveryAnticancer agentsFlutamideDensity-functional theoryBenzimidazolone capsuleGemcitabine
spellingShingle Kaynat Akhtar
Sehrish Sarfaraz
Muhammad Yar
Malai Haniti Sheikh Abdul Hamid
Nadeem S. Sheikh
Khurshid Ayub
DFT investigation of therapeutic potential of benzimidazolone capsule as a drug delivery vehicle for anticancer drug
Scientific Reports
Drug delivery
Anticancer agents
Flutamide
Density-functional theory
Benzimidazolone capsule
Gemcitabine
title DFT investigation of therapeutic potential of benzimidazolone capsule as a drug delivery vehicle for anticancer drug
title_full DFT investigation of therapeutic potential of benzimidazolone capsule as a drug delivery vehicle for anticancer drug
title_fullStr DFT investigation of therapeutic potential of benzimidazolone capsule as a drug delivery vehicle for anticancer drug
title_full_unstemmed DFT investigation of therapeutic potential of benzimidazolone capsule as a drug delivery vehicle for anticancer drug
title_short DFT investigation of therapeutic potential of benzimidazolone capsule as a drug delivery vehicle for anticancer drug
title_sort dft investigation of therapeutic potential of benzimidazolone capsule as a drug delivery vehicle for anticancer drug
topic Drug delivery
Anticancer agents
Flutamide
Density-functional theory
Benzimidazolone capsule
Gemcitabine
url https://doi.org/10.1038/s41598-025-12817-7
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