PMID- 36097681 OWN - NLM STAT- MEDLINE DCOM- 20221026 LR - 20230410 IS - 2047-4849 (Electronic) IS - 2047-4830 (Linking) VI - 10 IP - 21 DP - 2022 Oct 25 TI - Designing coordination polymers as multi-drug-self-delivery systems for tuberculosis and cancer therapy: in vitro viability and in vivo toxicity assessment. PG - 6201-6216 LID - 10.1039/d2bm00752e [doi] AB - A proof of concept for designing multi-drug-delivery systems suitable for self-drug-delivery is disclosed. Simple coordination chemistry was employed to anchor two kinds of drugs namely isoniazid (IZ - anti-tuberculosis), various non-steroidal-anti-inflammatory-drugs (NSAIDs) namely ibuprofen-IBU, fenoprofen-FEN, naproxen-NAP, diclofenac-DIC and mefenamic acid-MEF and Zn(NO(3))(2) to synthesize a series of 1D coordination polymers namely IZIBU, IZFEN, IZNAP, IZDIC and IZMEF which were structurally characterized by single crystal X-ray diffraction (SXRD). The coordination polymers wherein both types of drugs were anchored to Zn(II) metal centers could easily be ground to nano-sized particles suitable for biological studies by hand grinding in a mortar and pestle. Zone inhibition studies revealed that all the coordination polymers possessed antibacterial properties against Gram positive, Gram negative and mycobacteria namely Mycobacterium tuberculosis (M.tb). Detailed studies carried out on IZDIC employing flow cytometry and confocal microscopy under various staining conditions established that such antibacterial activity was due to the generation of reactive oxygen species (ROS) such as nitric oxide (NO) and also inhibition of mycolic acid leading to incomplete cell wall formation. It was also established that IZDIC could indeed inhibit the growth of M.tb within a mouse macrophage host cell namely RAW 264.7 thereby simulating the treatment of Tuberculosis (TB) under in vitro conditions. Scratch assay and cell cycle analysis on a human lung cancer cell line (A549) revealed its anti-cancer property, thereby indicating its potential as a multi-drug-delivery system. In vivo toxicity assessment (serum parameters, histopathology, and haemolysis) carried out on BALB/c mice showed that IZDIC was safe up to a concentration of 100 mg kg(-1). Finally, a reasonably high yield in bulk synthesis, stability under high temperature and humid conditions, tabletability and, slow and sustained release of the drug component of IZDIC suggested its suitability in real-life applications as multi-drug-delivery systems. FAU - Biswas, Protap AU - Biswas P AUID- ORCID: 0000-0002-3757-4951 AD - School of Chemical Sciences, Indian Association for the Cultivation of Science (IACS), 2A and 2B Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, West Bengal, India. ocpd@iacs.res.in. FAU - Datta, Hemanta Kumar AU - Datta HK AD - School of Chemical Sciences, Indian Association for the Cultivation of Science (IACS), 2A and 2B Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, West Bengal, India. ocpd@iacs.res.in. FAU - Dastidar, Parthasarathi AU - Dastidar P AUID- ORCID: 0000-0002-1011-2386 AD - School of Chemical Sciences, Indian Association for the Cultivation of Science (IACS), 2A and 2B Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, West Bengal, India. ocpd@iacs.res.in. LA - eng PT - Journal Article DEP - 20221025 PL - England TA - Biomater Sci JT - Biomaterials science JID - 101593571 RN - 0 (Polymers) RN - 57Y76R9ATQ (Naproxen) RN - V83O1VOZ8L (Isoniazid) RN - 0 (Reactive Oxygen Species) RN - WK2XYI10QM (Ibuprofen) RN - 367589PJ2C (Mefenamic Acid) RN - 144O8QL0L1 (Diclofenac) RN - 0 (Mycolic Acids) RN - RA33EAC7KY (Fenoprofen) RN - 31C4KY9ESH (Nitric Oxide) RN - 0 (Delayed-Action Preparations) RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Anti-Bacterial Agents) SB - IM MH - Mice MH - Animals MH - Humans MH - Polymers/chemistry MH - Naproxen MH - Isoniazid/pharmacology MH - Reactive Oxygen Species MH - Ibuprofen MH - Mefenamic Acid MH - Diclofenac MH - Mycolic Acids MH - Fenoprofen MH - Nitric Oxide MH - Delayed-Action Preparations MH - *Tuberculosis/drug therapy/microbiology MH - Drug Delivery Systems MH - *Mycobacterium tuberculosis MH - Anti-Inflammatory Agents, Non-Steroidal/chemistry MH - Anti-Bacterial Agents EDAT- 2022/09/14 06:00 MHDA- 2022/10/27 06:00 CRDT- 2022/09/13 02:33 PHST- 2022/09/14 06:00 [pubmed] PHST- 2022/10/27 06:00 [medline] PHST- 2022/09/13 02:33 [entrez] AID - 10.1039/d2bm00752e [doi] PST - epublish SO - Biomater Sci. 2022 Oct 25;10(21):6201-6216. doi: 10.1039/d2bm00752e.