Treatment of epithelial cysts by intracystic injection of antineoplastic particles
Inventors
diZerega, Gere S. • BALTEZOR, Michael • DECEDUE, Charles J. • Campbell, Sam • MCCLOREY, Matthew • Iacobucci, Marc • MAULHARDT, Holly
Assignees
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Publication Number
US-11523983-B2
Publication Date
2022-12-13
Expiration Date
Abstract
Disclosed herein are methods for treating epithelial cysts, including pancreatic cysts, in a subject by intracystic injection of compositions comprising antineoplastic particles, including taxane particles such as paclitaxel particles and docetaxel particles.
Core Innovation
The invention relates to treating benign epithelial cysts by intracystic injection of a composition directly into the cyst. The composition comprises an effective amount of paclitaxel particles and an aqueous liquid carrier, in which the paclitaxel particles are dispersed as a suspension for treating the benign epithelial cyst.
The paclitaxel particles comprise at least 95% of the paclitaxel, have a specific surface area of at least 18 m2/g, and have a mean particle size of from 0.1 microns to 5 microns. The composition comprises a suspension of the paclitaxel particles dispersed in the carrier and does not contain ethanol.
The described approach uses antineoplastic solid taxane particles in intracystic administration rather than paclitaxel in solution or albumin-bound paclitaxel, to create a suspension depot/residence effect in the cyst while reducing systemic toxicity. The document also includes an early Phase 2 open-label study of intracystic NANOPAC in mucinous pancreatic cystic neoplasms and preliminary cyst response observations.
Supporting characterization of taxane particle formulations and in-vitro membrane flux/release testing are described to support retention of nanoparticle formulations over solutions or albumin-bound paclitaxel. The testing includes membrane flux and release concepts described using porcine membranes and diffusion testing.
Claims Coverage
The provided material includes one independent claim directed to a method of treating a benign epithelial cyst by direct intracystic injection of a suspension of paclitaxel particles in an aqueous liquid carrier with multiple particle-property and formulation exclusions. Dependent claims refine the independent claim with additional limitations related to particle form, exclusions, delivery, and optional cyst-fluid volume matching.
Direct intracystic injection of paclitaxel particles suspension
Injecting a composition comprising an effective amount of paclitaxel particles and an aqueous liquid carrier directly into the benign epithelial cyst, thereby treating the benign epithelial cyst.
Paclitaxel particles composition and concentration constraints
The paclitaxel particles comprise at least 95% of the paclitaxel, and the composition comprises a suspension of the paclitaxel particles dispersed in the carrier.
Specific surface area and mean particle size ranges
The paclitaxel particles have a specific surface area of at least 18 m2/g, and the paclitaxel particles have a mean particle size of from 0.1 microns to 5 microns.
Ethanol-free aqueous suspension
The composition does not contain ethanol.
Crystalline paclitaxel particles
The paclitaxel particles are crystalline particles.
Albumin exclusion
The composition and paclitaxel particles exclude albumin.
Matched injection volume after cyst fluid withdrawal
The injected composition volume matches the volume of cyst fluid removed from a benign epithelial cyst.
EUS-guided fine needle injection delivery
Injecting the composition using endoscopic ultrasound-guided fine needle injection (EUS-FNI).
The core coverage is an ethanol-free aqueous suspension of paclitaxel particles with defined specific surface area and mean particle size, injected directly into a benign epithelial cyst. Dependent limitations further narrow to crystalline particles, exclude albumin, optionally match injected volume to withdrawn cyst fluid volume, and use EUS-FNI for delivery.
Stated Advantages
Longer residence/depot effect in the cyst compared with solutions.
Reduced systemic toxicity.
Reduced cyst volume/size and reduced growth rate.
Eliminated/ablated cyst and reduced pain.
Documented Applications
Treatment of benign epithelial cysts via intracystic injection of paclitaxel particles suspended in an aqueous liquid carrier.
Intracystic treatment of mucinous pancreatic cystic neoplasms using intracystic NANOPAC in a Phase 2 open-label study, including preliminary cyst response observations.
In-vitro membrane flux/release testing using porcine membranes and diffusion testing concepts to support retention of nanoparticle formulations over solutions or albumin-bound paclitaxel.
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