title: Molecular Inclusion Complexes of β-Cyclodextrin Derivatives Enhance Aqueous Solubility and Cellular Internalization of Paclitaxel: Preformulation andIn vitroAssessments.
abstract: Drugs with low aqueous solubility and permeability possess substantial challenges in designing effective and safe formulations. Synergistic solubility and permeability enhancement in a simple formulation can increase bioavailability and efficacy of such drugs. To overcome limitations of the clinical formulation of Taxol®, Paclitaxel (PTX) was reformulated with various β-cyclodextrin (CD) derivatives suitable for parenteral administration. Results indicated that β-CDs can efficiently form complexes with PTX at lower molar ratios, enhance aqueous solubility up to 500 times and improved cellular internalization of PTX. All β-CD derivatives were found to be safe as excipient since none showed detectable signs of cyto-genotoxicity. As a result, the CD-PTX complexes significantly increased the cytotoxicity of the drug. The study concluded that CD-PTX formulations could substitute the current intravenous infusion of PTX obviating the use of non-inert excipient Cremophor EL.
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Milin
authors.initials: M
authors.lastname: Shah
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Vatsal
authors.initials: V
authors.lastname: Shah
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Anasuya
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA ; New Jersey Center for Biomaterials, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Minko
keywords: Compounds; Cyclodextrins; Enhancement; Inclusion; Permeability enhancement; Preformulation; Solubility