Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Abstract

The grim prognosis for patients diagnosed with malignant gliomas necessitates the development of new therapeutic strategies for localized and sustained drug delivery to combat tumor drug resistance and regrowth. Here we introduce drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy (DREAM BIG therapy). DREAM BIG therapy is envisioned to deliver three chemotherapeutics, temporally staged over one year, via a bioadhesive, biodegradable spray directly to the brain surgical site after tumor excision. In this proof-of-principle article exploring key components of the DREAM BIG therapy prototype, rhodamine B (RB) encapsulated poly(lactic-co-glycolic acid) and immunoglobulin G (IgG) encapsulated poly(lactic acid) microspheres were formulated and characterized. The encapsulation efficiency of RB and IgG and the release kinetics of the model drugs from the microspheres were elucidated in addition to the release kinetics of RB from poly(lactic-co-glycolic acid) microspheres formulated in a degradable poly(N-isopropylacrylamide) solution. The successful aerosolized application onto brain tissue ex-vivo demonstrated the conformal adhesion of the RB encapsulated poly(lactic-co-glycolic acid) microspheres to the convoluted brain surface mediated by the thermoresponsive carrier, poly(N-isopropylacrylamide). These preliminary results suggest the potential of the DREAM BIG therapy for future use with multiple chemotherapeutics and microsphere types to combat gliomas at a localized site.