Efficient Drug Delivery of Paclitaxel Glycoside: A Novel Solubility Gradient Encapsulation into Liposomes Coupled with Immunoliposomes Preparation

Abstract

Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7-glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside.

Hyaluronic Acid Mediated Enrichment of CD44 Expressing Glioblastoma Stem Cells in U251MG Xenograft Mouse Model

“…Further the establishment of the model system will be advantageous for the replenishment of CSC, as in long turn in vitro culture system these cells undergo differentiation to normal cancer cells. Enrichment of CD44 expressing cells would be a better platform in the drug targeting experiments for CSCs as we previously successfully showed targeting HER2 breast cancer cells with our bionanocapsule [37] and liposome [38,39] with HER2-binding artificial ligands and such models will provide extensive knowledge in the therapeutic intervention in curbing the cancer growth and metastasis. The advantage of our model involves its cost-effective enrichment of the CD44 expressing glioblastoma cells cells were the up regulation were found to be 2-fold when compared with adherent HA-conditions.…”

Recent advances in allelopathy for weed control: from knowledge to applications

“…Several studies in recent years have been aimed at enhancing the solubility of natural products without modification of the chemical structure, a process that can change the bioactivity of the active compound. 229,230 One of the best ideas in this area is the use of encapsulation, a procedure that is extensively discussed in an article of this Special Issue. [231][232][233][234] It is possible to encase insoluble/sparingly soluble compounds within other compounds that have higher solubility.…”

Liposomes derivatized with multimeric copies of KCCYSL peptide as targeting agents for HER-2-overexpressing tumor cells

“…Herceptin molecule or its fragments (Fab or ScFv) have been also used to decorate nanoparticles or liposomes for the selective delivery of anticancer drugs such as doxorubicin 4 or paclitaxel 5 to HER-2-positive tumors. Compared with large molecules such as antibodies and their derivatives, smaller peptide molecules appear to be more attractive targeting moieties because of their less expensive and simple production, lack of immunogenicity, chemical stability, and flexibility in the choice of conjugation procedures to the carrier's surface.…”