Encapsulation of Naproxen with Meso-Tetradodecyl-Pyrogallol[4]arene: Complexation, Characterization, and Molecular Docking Insights: Enkapsulasi Naproksen dengan Meso-Tetradodecyl-Pyrogallol[4]arene: Pembentukan Kompleks, Karakterisasi, dan Wawasan Docking Molekuler

Essam S. Khudhier (Department of Pharmaceutical Chemistry, College of Pharmacy, Basrah University, Basrah)
Maan S. AlNuaim (Department of Pharmaceutical Chemistry, College of Pharmacy, Basrah University, Basrah)
Khulood H. Oudah (Department of Pharmacy, Mazaya University College, Nasiriyah 64001)

Indonesian Journal Health Science and Medicine
Vol. 3 No. 1 (2026): July

General Background: Supramolecular encapsulation using macrocyclic hosts has emerged as a strategy to address solubility and stability limitations of poorly water-soluble drugs. Specific Background: Naproxen, a widely prescribed nonsteroidal anti-inflammatory drug, exhibits low aqueous solubility and gastrointestinal irritation, prompting investigation of meso-tetradodecyl-pyrogallol[4]arene (C12-Py[4]arene) as a hydrophobic macrocyclic carrier capable of forming inclusion complexes through noncovalent interactions. Knowledge Gap: Although pyrogallol[4]arenes possess tunable cavities and self-assembly properties, detailed characterization of naproxen encapsulation combining spectroscopic, morphological, and molecular docking analyses remains limited. Aims: This study aimed to encapsulate naproxen within C12-Py[4]arene via mechanochemical grinding, characterize the resulting complex (PYX7), and evaluate binding affinity using molecular docking. Results: UV–Vis spectroscopy revealed bathochromic shifts at 318.00 and 332.50 nm, while FTIR analysis showed C=O band shifting from 1725 to 1689 cm⁻¹, confirming hydrogen bonding. SEM demonstrated altered semi-spherical agglomerates with heterogeneous morphology. Docking simulations predicted favorable binding energy (−7.00 kcal/mol), supported by hydrogen bonding and π–π stacking interactions within the hydrophobic cavity. Novelty: The integration of solvent-free complexation, spectroscopic validation, SEM imaging, and in silico modeling provides a comprehensive profile of PYX7 formation. Implications: These findings identify C12-Py[4]arene as a supramolecular carrier for naproxen and support further evaluation of pyrogallol[4]arene-based systems in NSAID delivery research. Keywords: Supramolecular Encapsulation, Naproxen, Pyrogallol4arene, Inclusion Complex, Molecular Docking Key Findings Highlights: Spectral shifts verified noncovalent host–guest interactions. Microscopy demonstrated nano-assembly formation with structural heterogeneity. Computational modeling showed favorable binding energetics and structural complementarity.