title: Hybrid liposomal PEGylated calix[4]arene systems as drug delivery platforms for curcumin.
abstract: The tremendous therapeutic potential of curcumin as a chemopreventive, antineoplastic and chemosensitizing agent has failed to progress towards clinical development and commercialization due to its unfavorable physicochemical properties, low aqueous solubility, chemical instability, and pharmacokinetics. The present contribution is focused on the feasibility of using PEGylated calixarene, in particular polyoxyethylene-derivatized tert-butylcalix[4]arene, to prepare various platforms for delivery of curcumin such as inclusion complex, supramolecular aggregates, and hybrid liposomal systems. The inclusion complex is characterized by UV-vis and FT-IR spectroscopy as well as thermal gravimetrical analysis and differential scanning calorimetry. At concentrations exceeding the critical micellization concentration of PEGylated calixarene, the tremendous solubility enhancement of curcumin is attributed to additional solubilization and hydrophobic non-covalent interactions of the drug with supramolecular aggregates. A hybrid liposomal system is created via encapsulation of the inclusion complex in dipalmitoylphosphatidylcholine:cholesterol liposomes. Bare and liposomal curcumin:BEC-X inclusion complexes, as well as free curcumin were additionally investigated for cytotoxicity and apoptogenic activity against human tumor cell lines.
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University - Sofia, 2 Dunav St., 1000 Sofia, Bulgaria.
authors: Elena
authors: E
authors: Drakalska
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University - Sofia, 2 Dunav St., 1000 Sofia, Bulgaria. Electronic address: dmomekova@yahoo.com.
authors: Denitsa
authors: D
authors: Momekova
authors: Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. Georgi Bonchev St. Bldg 9, 1113 Sofia, Bulgaria.
authors: Yana
authors: Y
authors: Manolova
authors: Institute of Polymers, Bulgarian Academy of Sciences, 103 Acad. Georgi Bonchev St., 1113 Sofia, Bulgaria.
authors: Dessislava
authors: D
authors: Budurova
authors: Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University - Sofia, 2 Dunav St., 1000 Sofia, Bulgaria.
authors: Georgi
authors: G
authors: Momekov
authors: Lab of Hematopathology, National Specialized Hospital for Active Treatment of Hematological Diseases, Sofia, Bulgaria.
authors: Margarita
authors: M
authors: Genova
authors: Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. Georgi Bonchev St. Bldg 9, 1113 Sofia, Bulgaria.
authors: Liudmil
authors: L
authors: Antonov
authors: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University - Sofia, 2 Dunav St., 1000 Sofia, Bulgaria.
authors: Nikolay
authors: N
authors: Lambov
authors: Institute of Polymers, Bulgarian Academy of Sciences, 103 Acad. Georgi Bonchev St., 1113 Sofia, Bulgaria.
authors: Stanislav
authors: S
authors: Rangelov
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D047250:Calixarenes / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes; D010636:Phenols / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D010636:Phenols; C121325:calix(4)arene; D047250:Calixarenes; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; D002784:Cholesterol; D003474:Curcumin
keywords: Calix[4]arenes; Curcumin; Cytotoxicity; Hybrid liposomal system; Inclusion complexes; Liposomes