Optimization of Ultra-Small Nanoparticles for Enhanced Drug Delivery
Shishi He, Yanni Fu, Zicong Tan, Qun Jiang, Kangling Huang, Phei Er Saw, Yan Nie, Mingyan Guo
Abstract
Abstract Nanoparticle delivery of drugs to the brain is hindered by the blood-brain barrier (BBB). In malignant glioma (MG), small disruptions in the BBB may allow nanoparticles smaller than 20 nm to penetrate the dysfunctional barrier. We previously developed ultra-small nanoparticles called hyper-cell permeable micelles (HCPMis) with a radius of ∼12 nm and found that a PEGylated HCPMi system showed enhanced cell permeability and cellular uptake, and remarkable anti-tumor properties in MG treatment. However, no study had examined the delivery of temozolomide (TMZ), the first-line drug for MG, with the HCPMi platform. Herein, we use a simple PEGylation increment system (30 wt % PEG, 40 wt % PEG and 50 wt % PEG) to develop a robust optimized HCPMi nanoplatform for TMZ delivery. All optimized HCPMi systems showed greater stability than the non-PEGylated parent formulation. Compared with commercially available micelles (DSPE-PEG 2000 ), all optimized HCPMi systems showed greater cellular uptake in vitro . Although a higher percentage of PEGylation was associated with better cellular uptake and anti-cancer properties, the difference was statistically insignificant. Furthermore, in vitro cytotoxicity assays revealed that all optimized HCPMi-encapsulated TMZ formulations showed significantly stronger anti-cancer properties than the parent drug TMZ and TMZ encapsulated DSPE-PEG 2000 , thus indicating the feasibility of using this nanoplatform for the delivery of TMZ to treat brain malignancies.