Injectable SN-38-embedded Polymeric Microparticles Promote Antitumor Efficacy against Malignant Glioma in an Animal Model

Abstract

Malignant glioma (MG) is extremely aggressive and highly resistant to chemotherapeutic agents. Using electrospraying, the potent chemotherapeutic agent 7-ethyl-10-hydroxycamptothecia (SN-38) was embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs). The SMPs were stereotactically injected into the brain parenchyma of healthy rats and intratumorally injected into F98 glioma-bearing rats for estimating the pharmacodynamics and therapeutic efficacy. SN-38 was rapidly released after injection and its local (brain tissue) concentration remained much higher than that in the blood for more than 8 weeks. Glioma-bearing rats were divided into three groups—group A (n = 13; stereotactically injected pure PLGA microparticles), group B (n = 12; stereotactically injected Gliadel wafer and oral temozolomide), and group C (n = 13; stereotactic and intratumoral introduction of SMPs). The SMPs exhibited significant therapeutic efficacy, with prolonged survival, retarded tumor growth, and attenuated malignancy. The experimental results demonstrated that SMPs provide an effective and potential strategy for the treatment of MG.

Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle

“…However, the high toxicity and instability of SN-38 in the physiological environment (pH 7.4) have made its clinical use infeasible [ 28 ]. In our previous study, we demonstrated that SMP-based interstitial delivery of SN-38 is feasible [ 31 ]. This therapeutic strategy, combined with orally administered TMZ, displayed increased anti-tumor activity in a rat model of malignant glioma.…”

“…In a previous study, we loaded SN-38 into poly(lactid-co-glycolid) (PLGA) microparticles (SMPs) using an electrospraying technique. SMPs were introduced into rat brain parenchyma via stereotactic techniques [ 31 ]. Our previous results suggested that SMPs are biocompatible and biodegradable [ 31 ].…”

“…SMPs were introduced into rat brain parenchyma via stereotactic techniques [ 31 ]. Our previous results suggested that SMPs are biocompatible and biodegradable [ 31 ]. SMPs were delivered intratumorally into tumor-bearing rats via stereotactical techniques; the results showed a sustained drug release pattern and significant therapeutic efficacy [ 31 ].…”

“…Our previous results suggested that SMPs are biocompatible and biodegradable [ 31 ]. SMPs were delivered intratumorally into tumor-bearing rats via stereotactical techniques; the results showed a sustained drug release pattern and significant therapeutic efficacy [ 31 ]. Most importantly, this drug delivery system has minimal systemic side effects [ 31 ].…”

“…SMPs were delivered intratumorally into tumor-bearing rats via stereotactical techniques; the results showed a sustained drug release pattern and significant therapeutic efficacy [ 31 ]. Most importantly, this drug delivery system has minimal systemic side effects [ 31 ]. Given the low toxicity of SN-38, using SMP-based interstitial delivery with SN-38 functions through a different mechanism of action than TMZ.…”