Nanoparticles comprising a cyclodextrin and a biologically active molecule and uses thereof

Inventors

Agüeros Bazo, Maite • Salman, Hesham H. A. • Irache Garreta, Juan Manuel • Campanero Martínez, Miguel Angel

Assignees

Innoup Farma SL

Abstract

The invention relates to nanoparticles comprising a biodegradable polymer, a cyclodextrin or a derivative thereof, and a biologically active molecule. Said nanoparticles can associate large amounts of biologically active molecules, especially of a hydrophobic nature, and release the biologically active molecule providing sustained and constant plasma levels thereof when they are administered orally or through any other mucosa of the organism.

Core Innovation

The invention relates to biodegradable polymer/cyclodextrin nanoparticles formulated for oral delivery of paclitaxel as a biologically active molecule. The nanoparticles are formed from a complex comprising 2-hydroxypropyl-β-cyclodextrin and paclitaxel, in which the paclitaxel is retained in a hydrophobic cavity of the 2-hydroxypropyl-β-cyclodextrin, and a methyl vinyl ether/maleic anhydride copolymer (PVM/MA) encapsulates the complex thereby forming the nanoparticle.

A key aspect is that the resulting nanoparticle prevents the action of a P-glycoprotein enzyme on paclitaxel, addressing the involvement of P-glycoprotein and the ABC transporter superfamily in paclitaxel handling. The nanoparticle uses a paclitaxel/2-hydroxypropyl-β-cyclodextrin molar ratio between 1:1 and 1:2 to form and retain the complex within the hydrophobic cavity.

The disclosed delivery concept is supported by reported performance comparisons showing sustained release with constant plasma levels for up to about 24 hours and improved oral bioavailability and absorption compared with conventional paclitaxel formulations and cyclodextrin complexes alone. The document reports bioadhesive interaction with gastrointestinal mucosa, including rat GI tract bioadhesion profiles and fluorescence microscopy observations of mucosal and enterocyte association, together with pharmacokinetic comparisons based on AUC, Cmax, Tmax, MRT, and half-life across different paclitaxel formulations.

Claims Coverage

Independent claim coverage is provided by one independent claim. It contains the core inventive features related to the specific paclitaxel/2-hydroxypropyl-β-cyclodextrin complex, PVM/MA encapsulation, prevention of P-glycoprotein action, and a defined paclitaxel/2-hydroxypropyl-β-cyclodextrin molar ratio between 1:1 and 1:2.

The independent claim defines an oral-delivery nanoparticle in which paclitaxel is retained in the hydrophobic cavity of a 2-hydroxypropyl-β-cyclodextrin complex, the complex is encapsulated by PVM/MA, the nanoparticle prevents P-glycoprotein action on paclitaxel, and the paclitaxel/2-hydroxypropyl-β-cyclodextrin molar ratio is between 1:1 and 1:2.

Stated Advantages

Documented Applications