Table 3:
Summary of Design Criteria for Nanoparticle Delivery to Glioblastoma
| Design Criterion | Optimal Parameters | Purpose | Examples/References |
|---|---|---|---|
| Hydrophobicity | Amphiphilic | Pass through BBB/cell membranes | Fully hydrophilic NPs flatten during membrane transport leading to more difficult passage while hydrophobic NPs elongate leading to easier diffusion; Amphiphilic NPs retain integrity while also passing through membrane relatively easily[265] |
| Size | >50 nm, <200 nm | Ensure penetration through ECS and cell uptake; Reduce NP clearance from Brain ECS | PLGA Brain Penetrating NPs[233], Polystyrene NPs of 200 nm and less demonstrate increased cell uptake and membrane transport[266], TPGS coated Polystyrene NPs demonstrate best uptake/transport at 100 nm compared to other sizes[267] |
| Surface Charge | Cationic | Uptake in Glioblastoma Stem Cells | Polyurethane-PEI NPs loaded with miR-145[268], PAMAM conjugated to PLGA-PEG NPs with paclitaxel[269] |
| Neutral/Neutral | Distribution through Brain ECS | PLGA Brain Penetrating NPs[233], Neutral and Anionic NPs less toxic than Cationic NPs[270] | |
| PEGylation | Dense Coating | Brain ECS Distribution/Reduce Clearance | Paclitaxel Polystyrene NPs coated with Dense PEG[234] |
| Surface Chemistry | Tumor-specific Targeting | Enhance tumor uptake/reduce off target cell uptake, BBB penetration | Transferrin-conjugated[271], Apolipoprotein E[245], Angiopep-2[272], RGD peptide[273], Antibody-conjugated (Cetuximab)[274] |
| Internal Chemistry | Hydrophobic; Biodegradation | Control release rate of cargo; Nanoparticle Stability | Poorly soluble drugs encapsulated better in hydrophobic NP core[275] |
| Surfactant Presence/Type | Surfactant Dependent | Prevent off target toxicities/Enhance cell uptake/Other Properties | Polysorbate-80-coating of PBCA NPs enhances uptake and BBB penetration[276], Poloxamer 188 increases PLGA NP size and Polyvinyl Alcohol decreases it[277] |
| Nanoparticle Structure | Solid Nanoparticle | Prevent disruption of NP during transport and different media | Core-shell Spherical PLGA-PEG NP structure prevents destabilization by salt solution compared to PLGA NPs[278] |