Exploring high pressure nebulization of Pluronic F127 hydrogels for intraperitoneal drug delivery

• Published in: European journal of pharmaceutics and biopharmaceutics 2021-12, Vol.169, p.134-143
• Main Authors: Braet, Helena, Rahimi-Gorji, Mohammad, Debbaut, Charlotte, Ghorbaniasl, Ghader, Van Walleghem, Thibault, Cornelis, Senne, Cosyns, Sarah, Vervaet, Chris, Willaert, Wouter, Ceelen, Wim, De Smedt, Stefaan C., Remaut, Katrien
• Format: Article
• Language: English
• Subjects: Aerosolized Particles and Droplets - pharmacology; Antineoplastic Agents - pharmacology; Computational fluid dynamics; Controlled release; Delayed-Action Preparations - pharmacology; Drug Compounding - methods; Excipients - pharmacology; Humans; Hydrodynamics; Hydrogels; Hydrogels - pharmacology; Intraperitoneal drug delivery; Nanoparticles - therapeutic use; Nebulization; Nebulizers and Vaporizers; Peritoneal Absorption - drug effects; Peritoneal Neoplasms - secondary; Peritoneal Neoplasms - therapy; PIPAC; Poloxamer - pharmacology; Tissue Distribution
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2021.10.001

[Display omitted] Peritoneal metastasis is an advanced cancer type which can be treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Here, chemotherapeutics are nebulized under high pressure in the intraperitoneal (IP) cavity to obtain a better biodistribution and tumor penetration. To prevent the fast leakage of chemotherapeutics from the IP cavity, however, nebulization of controlled release formulations is of interest. In this study, the potential of the thermosensitive hydrogel Pluronic F127 to be applied by high pressure nebulization is evaluated. Therefore, aerosol formation is experimentally examined by laser diffraction and theoretically simulated by computational fluid dynamics (CFD) modelling. Furthermore, Pluronic F127 hydrogels are subjected to rheological characterization after which the release of fluorescent model nanoparticles from the hydrogels is determined. A delicate equilibrium is observed between controlled release properties and suitability for aerosolization, where denser hydrogels (20% and 25% w/v Pluronic F127) are able to sustain nanoparticle release up to 30 h, but cannot effectively be nebulized and vice versa. This is demonstrated by a growing aerosol droplet size and exponentially decreasing aerosol cone angle when Pluronic F127 concentration and viscosity increase. Novel nozzle designs or alternative controlled release formulations could move intraperitoneal drug delivery by high pressure nebulization forward.