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Nanogel has attracted considerable attention as one of the most versatile drug delivery systems, especially for site-specific and/or time-controlled delivery of the chemotherapeutic agent. The main objective of this study was to prepare the polymeric nanogel characterized by Fourier transform infrared spectroscopy, x-ray diffraction, thermogravimetric analysis, differential scanning, and oral acute toxicity. Free radical polymerization was done for the fabrication of polymeric nanogel. Fourier transform infrared spectroscopy was used to confirm the successful free radical polymerization. Various techniques such as x-ray diffraction, differential scanning calorimetric, and thermogravimetric analysis measurement were used to investigate the thermal behavior and crystallinity of developed nanogel. Parameters such as swelling, drug loading, and in vitro drug release is enhanced as polymers and monomers concentrations increase while these parameters decrease in case of increasing crosslinker concentration. The oral biocompatibility results of developed nanogel exhibited no toxicity in rabbits. Histopathological changes were observed between empty and loaded group. The nanosized gel offers a specific surface area which increases the stability of loaded drug (oxaliplatin) and bioavailability of the drug (oxaliplatin) as compared to the conventional drug delivery systems., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The reactivity of platinum-containing drugs such as cisplatin, carboplatin, and oxaliplatin is essential for its mechanism of action as an anticancer agent. This inherent reactivity means that molecules in tools used to study these metal-based drugs such as solvents (DMSO), cell culture media, and other buffer additives can ligate to and inactivate or activate them. This Commentary considers these cautionary tales in the context of a new report that cisplatin can also react with penicillin, reiterates best practice in creating Pt drug stock solutions, and highlights the significant work that remains to fully characterize the fate of cisplatin in cell culture media., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Determination of the toxicity of compounds toward cancer cells is a frequent procedure in drug discovery. For metal complexes, which are often reactive prodrugs, care has to be taken to consider reactions with components of the cell culture medium that might change the speciation of the metal complex before it is taken up by the cells. Here, we consider possible reactions between the clinical platinum drugs cisplatin and oxaliplatin with penicillin G, an antibiotic added routinely to cell culture media to prevent bacterial contamination. Platinum has a high affinity for ligands with sulfur donors. Penicillin G is an unstable thioether that degrades in a range of pathways. Nuclear magnetic resonance (NMR) and UV-Vis absorption spectroscopic studies show that reactions with cisplatin can occur within minutes to hours at 310 K, but more slowly with oxaliplatin. The identities of the Pt- adducts were investigated by mass spectrometry. The marked effect on cytotoxicity of co-incubation of cisplatin with penicillin G was demonstrated for the HeLa human cervical cancer cell line. These studies highlight the possibility that reactions with penicillin G might influence the cytotoxic activity of metal complexes determined in culture media., (© 2022. The Author(s).)

The results of theoretical simulations of reaction paths for oxaliplatin from pro-drug into its active form responsible for cytostatic effect are presented. The studies based on the quantum-chemical density functional theory approach were performed considering environmental influence resulting from the aquation or electron donation. The hybrid mechanisms: hydrolytic mixed with electron driven were found to be the energetically favourable.

The synthesis of the platinum(II) complexes, [Pt(AIP)(bpy)](PF 6 ) 2 (1) and [Pt(PIP)(phen)](PF 6 ) 2 (2), of anthracene- and pyrene-conjugated imidazophenanthroline ligands and their in vitro cytotoxicity toward the fibroblast cells and the HeLa cell lines are reported. MTT assay demonstrates their cytotoxicity against the HeLa cell lines with the IC 50 values of 1.35 and 1.56 µM, respectively, and the cytotoxicity profiles indicate that the HeLa cell lines show more activity than the fibroblast cells. Trypan blue assay highlights significant damage on the HeLa cell lines with a pronounced reduction on their clonogenicity. AO/EB staining shows marked morphologic signs of apoptosis in a dose-dependent manner and the LDH and DNA laddering assays also lend support to the cytotoxicity of the complexes. The molecular docking study reveals that the complexes interact with DNA through hydrogen bonding. The TD-DFT energy-optimized structures of the complexes show that the platinum(II) center has a slightly distorted square-planar geometry. The TD-DFT modelled LUMOs receive major contributions from the platinum d-orbitals, while the HOMOs are delocalized largely on the anthracenyl- and pyrenyl ligands, resulting in the LMCT transition at 352 nm. The structural, bonding, electronic, and optical properties of the complexes 1 and 2 reported in the present work and that of [Pt(AIP)(phen)](PF 6 ) 2 (3) and [Pt(PIP)(bpy)](PF 6 ) 2 (4), reported by us recently, and the approved drugs cisplatin, carboplatin, and oxaliplatin are described in the light of the optimized geometries, ΔE HOMO-LUMO , polarizability (α), hyperpolarizability (β), Mulliken negativities, and dipole moments computed from the ab initio and DFT computational studies. The synthesis of Pt(II) complexes of anthracene- and pyrene-appended imidazophenanthroline ligands and their in vitro cytotoxicity against fibroblast cells and HeLa cell lines are reported. The DFT computational study of the complexes and cisplatin, carboplatin, and oxaliplatin are described in search of the ligand design features for the development of new Pt-drugs.