Polymeric Nanoparticles Properties and Brain Delivery
Abstract
:1. Introduction
2. Nanoparticle Size
3. Nanoparticle Shape
4. Nanoparticle Stiffness
5. Nanoparticle Surface Characteristics
5.1. Surface Charge
5.2. Ligand Density and Linker Length
5.3. Targeting Ligands
5.3.1. Glucose and Glucose Derivatives—Glucose Transporters
5.3.2. Transferrin, Anti-Transferrin Antibodies, and Transferrin Receptor Targeting Peptides—Transferrin Receptor
5.3.3. Peptides
G23 Peptide
Angiopep-2, Apolipoprotein E, and Other Low-Density Lipoprotein Receptor-Related Protein 1(LRP1) Ligands—LRP1 Receptor
RGD Peptide
Glutathione
RVG Peptide
TGN Peptide
5.3.4. Aptamers
5.3.5. Cell Membrane Coating
5.4. Avidity
5.5. Protein Corona
6. Concluding Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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NP Property | Effect on Brain Delivery | Advantages | Limitations |
---|---|---|---|
Size | Smaller sizes tend to benefit transport across the BBB. | NP size can be controlled through different methods. | Preparation of smaller polymeric NPs is still challenging, and size population homogeneity is often depreciated. |
Brain accumulation is shown to be higher for smaller NPs. | Size control may improve brain accumulation. | Loading of molecules may be low for small sized NPs. | |
Smaller NPs are more prone to clearance by the kidneys, while bigger NPs tend to be cleared by the spleen. | |||
Shape | Specific interactions may be favored in ligand-functionalized NPs. | Specific NP shapes may increase cell adhesion, e.g., rods. | Synthesis methods are not yet straightforward or broadly applicable. |
May reduce internalization by cells because more energy is required for wrapping. | |||
Stiffness | Stiffer NPs usually display increased uptake but are not necessarily more transcytosed. | Softer particles display reduced protein adsorption. | Uptake of softer NPs by cells is most likely reduced, which may limit treatment efficacy. |
NP brain accumulation is dependent on stiffness. | Variety of methodologies available to control stiffness. | The influence of other physicochemical properties might not allow setting an unequivocal threshold for an extensive range of particles. | |
Effects are highly dependent on the range of stiffness (often Young’s module). | Softer particles may be used to evade the MPS and enhance brain accumulation. | Stiffness modulation may not be trivial to all systems and all stiffnesses ranges. | |
NPs stiffness might not be homogeneous through the particle. | |||
Charge | Negatively charged surface of endothelial cells favors interaction with positively charged particles. | Control over surface charge may be used to diminish accumulation in endothelial cells and improve transport across the BBB. | Higher uptake does not necessarily lead to higher transcytosis, as positively charged particles might remain trapped in the endothelial cells to a larger extent. |
Positively charged NPs show higher uptake but lower transport across cells barriers compared with negatively charged NPs. | Positively charged particles may induce toxicity, increase ROS, and affect BBB integrity. | ||
Ligands | May increase targetability | Improves specificity. | Targeting ability may be limited by protein corona formation. |
May increase transcytosis but also depends on ligand density and affinity. | Versatility of conjugation techniques. | Unspecific-site functionalization strategies may reduce receptor-ligand interaction; additionally, populations heterogeneity is expected. | |
Variety of ligands. | Specific targets must be previously identified. | ||
Use of multiple ligands for dual- or multi-targeting. | Size increases due to functionalization. | ||
Some ligands are costly and hard to produce and purify, e.g., antibodies. | |||
Avidity | Transcytosis is boosted by tuning ligand density and avoiding enduring attachment of particles to the endothelial cells membrane. | Control of the endocytosis, sorting, and exocytosis in endothelial cells. | Controlled ligand density is not trivial. |
Avidity regulates the levels and location of NPs in the brain. | Improvement in the therapeutic index of drug delivery systems. | Engineering and production of ligands with different affinities is complex. | |
Enhance uptake by target cell. | |||
Corona | Presence of specific proteins, e.g., Apo E, may enhance NPs transport across the BBB and accumulation in the brain. | May reduce particle toxicity. | Alters size, shape, and surface properties. |
May improve particle targetability. | May hamper targetability of ligand-functionalized NPs by masking the ligands. | ||
Affects predictability of NPs–biological environment interaction. |
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Ribovski, L.; Hamelmann, N.M.; Paulusse, J.M.J. Polymeric Nanoparticles Properties and Brain Delivery. Pharmaceutics 2021, 13, 2045. https://doi.org/10.3390/pharmaceutics13122045
Ribovski L, Hamelmann NM, Paulusse JMJ. Polymeric Nanoparticles Properties and Brain Delivery. Pharmaceutics. 2021; 13(12):2045. https://doi.org/10.3390/pharmaceutics13122045
Chicago/Turabian StyleRibovski, Laís, Naomi M. Hamelmann, and Jos M. J. Paulusse. 2021. "Polymeric Nanoparticles Properties and Brain Delivery" Pharmaceutics 13, no. 12: 2045. https://doi.org/10.3390/pharmaceutics13122045
APA StyleRibovski, L., Hamelmann, N. M., & Paulusse, J. M. J. (2021). Polymeric Nanoparticles Properties and Brain Delivery. Pharmaceutics, 13(12), 2045. https://doi.org/10.3390/pharmaceutics13122045