title: Dendrimer-TPGS mixed micelles for enhanced solubility and cellular toxicity of taxanes.
abstract: Taxanes are the most effective, efficient and broad spectrum anticancer drugs for the treatment of various cancers. However, poor aqueous solubility is the major problem in their delivery at higher concentrations in cancer cells. In this research work, poor solubility of taxanes is addressed by preparing dendrimer and d-α-tocopherol polyethylene glycol succinate (TPGS) mixed micelles by taking into consideration the advantages of TPGS such as solubility enhancement and P-glycoprotein inhibition. Dendrimer-TPGS mixed micelles were prepared by solvent casting method. Docetaxel (DTX) and paclitaxel (PTX) were chosen as model drugs representing the group of taxanes. Nanomicelles were characterized by DLS, FTIR, PXRD, in vitro drug release and hemolytic studies. Effects of pH and dendrimer to TPGS ratio on the solubility of taxanes were also studied. Solubility of DTX and PTX were increased by 20.36 and 34.95 folds, respectively, when formulated in dendrimer-TPGS mixed micelles. Drug release studies exhibited better release profile of encapsulated drug at acidic pH which is advantageous in enhanced intracellular drug release in cancer cells. Formulations were found to be biocompatible in hemolytic toxicity assay. Cytotoxicity studies revealed that anticancer activities of both drugs were enhanced after encapsulation in micelles against cancer cells while caused very low toxicity to normal cells. Thus, dendrimer-TPGS mixed micelles are promising alternate for delivery of poorly water-soluble drugs taxanes.
authors: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Faculty of Pharmacy, College of Technology, Osmania University, Hyderabad, India.
authors: Deep
authors: D
authors: Pooja
authors: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; IICT-RMIT Research Centre, CSIR-Indan Institute of Chemical Technology, Hyderabad, India.
authors: Hitesh
authors: H
authors: Kulhari
authors: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors: Mayank K
authors: MK
authors: Singh
authors: Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
authors: Sudip
authors: S
authors: Mukherjee
authors: Faculty of Pharmacy, College of Technology, Osmania University, Hyderabad, India.
authors: Shyam Sunder
authors: SS
authors: Rachamalla
authors: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: sistla@iict.res.in.
authors: Ramakrishna
authors: R
authors: Sistla
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D000077143:Docetaxel; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014961:X-Ray Diffraction
chemical_list: D050091:Dendrimers; D008823:Micelles; D043823:Taxoids; D014810:Vitamin E; D000077143:Docetaxel; D011092:Polyethylene Glycols; C014225:tocophersolan; D017239:Paclitaxel
keywords: Mixed micelles; Poly(amidoamine) dendrimers; Solubility; TPGS; Taxanes