title: Water-Soluble Pd8L4Self-assembled Molecular Barrel as an Aqueous Carrier for Hydrophobic Curcumin.
abstract: A tetrafacial water-soluble molecular barrel (1) was synthesized by coordination driven self-assembly of a symmetrical tetrapyridyl donor (L) with a cis-blocked 90° acceptor [cis-(en)Pd(NO3)2] (en = ethane-1,2-diamine). The open barrel structure of (1) was confirmed by single crystal X-ray diffraction. The presence of a hydrophobic cavity with large windows makes it an ideal candidate for encapsulation and carrying hydrophobic drug like curcumin in an aqueous medium. The barrel (1) encapsulates curcumin inside its molecular cavity and protects highly photosensitive curcumin from photodegradation. The photostability of encapsulated curcumin is due to the absorption of a high proportion of the incident photons by the aromatic walls of 1 with a high absorption cross-sectional area, which helps the walls to shield the guest even against sunlight/UV radiations. As compared to free curcumin in water, we noticed a significant increase in solubility as well as cellular uptake of curcumin upon encapsulation inside the water-soluble molecular barrel (1) in aqueous medium. Fluorescence imaging confirmed that curcumin was delivered into HeLa cancer cells by the aqueous barrel (1) with the retention of its potential anticancer activity. While free curcumin is inactive toward cancer cells in aqueous medium at room temperature due to negligible solubility, the determined IC50value of ∼14 μM for curcumin in aqueous medium in the presence of the barrel (1) reflects the efficiency of the barrel as a potential curcumin carrier in aqueous medium without any other additives. Thus, two major challenges of increasing the bioavailability and stability of curcumin in aqueous medium even in the presence of UV light have been addressed by using a new supramolecular water-soluble barrel (1) as a drug carrier.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Imtiyaz Ahmad
authors.initials: IA
authors.lastname: Bhat
authors.affiliation: Department of Molecular Reproduction, Development and Genetics and Centre for Biosystems Science and Engineering, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Jain
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Mujahuddin M
authors.initials: MM
authors.lastname: Siddiqui
authors.affiliation: Department of Molecular Reproduction, Development and Genetics and Centre for Biosystems Science and Engineering, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Saini
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Partha Sarathi
authors.identifier: http://orcid.org/0000-0001-6891-6697
authors.initials: PS
authors.lastname: Mukherjee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000528:radiation effects / Q000633:toxicity; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000528:radiation effects / Q000633:toxicity; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D046911:Macromolecular Substances / Q000138:chemical synthesis / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity; D010165:Palladium / Q000737:chemistry*; D012995:Solubility; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004337:Drug Carriers; D008024:Ligands; D046911:Macromolecular Substances; D014867:Water; D010165:Palladium; D003474:Curcumin