Sustained adjunct therapy to improve chemotherapy efficacy in glioblastoma in a cerebrovascula tumor-on-a-chip model
AssigneeOhio State Innovation Foundation
InventorsAleksander Skardal, Katelyn Reilly, Rengasayee Veeraraghavan
Life of this patent
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Abstract
A cerebrovascular unit tumor (CVU-T)-on-a-chip model that models both the blood brain barrier (BBB) and tumor is described. The model provided a physiologically relevant GBM tumor model including a corresponding microenvironment complete with a BBB component that is crucial in dictating drug bioavailability to the tumor. Additionally a novel biodegradable microcapsule for sustained local delivery of a therapeutic such as a connexin hemichannel inhibitor is provided. The therapeutic sensitizes malignant GBM populations to systemic TMZ chemotherapy.
Claims27
A biodegradable microcapsule device comprising
- a luminal core compartment comprising a medication or adjuvant;
- an inner layer of biodegradable polymers surrounding the core;
- an outer layer surrounding and adhered to the inner layer;
- nanopores throughout the microcapsule;
- the microcapsule being sealed.
A method of making a microcapsule comprising:
- providing means to form a luminal core compartment;
- making an inner layer by collecting chitosan nanofibers, chitosan, a polyethyleneimine, a protamine, a polypropylimine, a poly-L-lysine, a poly-L-arginine, a poly-D-lysine, a poly-D-arginine, a cellulose, a dextran, a poly(amidoamine), poly(2-(dimethylamino)ethyl methacrylate), derivatives thereof, or combinations thereof on the luminal core means by electrospinning;
- making an outer layer by collected PCL nanofibers, a poly(e-caprolactone) (PCL), a poly-lactic acid (PLA), a poly-glycolic acid (PGA), a poly-lactide-co-glycolide (PLGA), a polyester, a poly(ortho ester), a poly(phosphazine), a poly(phosphate ester), a gelatin, a collagen, a polyethylene glycol (PEG), derivatives thereof, or combinations thereof on the inner layer by electrospinning;
- sintering the electrospun materials to remove macroscale pores;
- removing the luminal core means, creating a hollow luminal core compartment;
- salt leaching the hollow microcapsule to create a nonporous structure;
- sealing any open edges of the hollow microcapsule,
- inserting a medication or adjuvant into the hollow microcapsule;
- sealing any port opened by the insertion of the medication or adjuant, thereby enclosing the medication or adjuvant within the inner and outer layers and forming a microcapsule.
A method of administering a medication or adjuvant to a subject in need of treatment, the method comprising:
- implanting in or proximal to an area in need of treatment one or more biodegradable microcapsule device loaded with a medication or adjuvant, the microcapsule providing sustained release of the medication or adjuvant proximal to an area in need of treatment for a period of time
A method of administering to a subject in need to treatment for a cancer a therapeutic, the method comprising:
- coincident with surgical cancer removal from the subject, implanting in a tumoral area at least one biodegradable microcapsule device loaded with a medication or adjuvant, the microcapsule providing sustained release of the medication or adjuvant to the tumoral area for a period of time;
- and
- treating the subject post-surgically with a therapeutic that crosses the blood brain barrier.
Dependencies are inferred from the claim text.