Nanoparticle drug delivery
[1] Nanomaterials exhibit different chemical and physical properties or biological effects compared to larger-scale counterparts that can be beneficial for drug delivery systems.
Some important advantages of nanoparticles are their high surface-area-to-volume ratio, chemical and geometric tunability, and their ability to interact with biomolecules to facilitate uptake across the cell membrane.
By functionalizing nanoparticle surfaces with ligands that enhance drug binding, suppress immune response, or provide targeting/controlled release capabilities, both a greater efficacy and lower toxicity are achieved.
For example, liposome-based nanoparticles can be biologically degraded after delivery,[6] thus minimizing the risk of accumulation and toxicity after the therapeutic cargo has been released.
[16] Dendrimers are unique hyper-branched synthetic polymers with monodispersed size, well-defined structure, and a highly functionalized terminal surface.
[20] Dendrimers are also confined within a narrow size range (<15 nm) and current synthesis methods are subject to low yield.
The surface groups will reach the de Gennes dense packing limit at high generation level, which seals the interior from the bulk solution – this can be useful for encapsulation of hydrophobic, poorly soluble drug molecules.
Inorganic nanoparticles have been largely adopted to biological and medical applications ranging from imaging and diagnoses to drug delivery.
Quantum dots (QDs), or inorganic semiconductor nanocrystals, have also emerged as valuable tools in the field of bionanotechnology because of their unique size-dependent optical properties and versatile surface chemistry.
Their diameters (2 - 10 nm) are on the order of the exciton Bohr radius, resulting in quantum confinement effects analogous to the "particle-in-a-box" model.
Manipulation of nanocrystal core composition, size, and structure changes QD photo-physical properties Designing coating materials which encapsulate the QD core in an organic shell make nanocrystals biocompatible, and QDs can be further decorated with biomolecules to enable more specific interaction with biological targets.
Under aerobic and anaerobic conditions, it was found that copper, silver, and titanium nanoparticles released low or insignificant levels of metal ions.
This is evidence that copper, silver, and titanium NP are slow to release metal ions, and may therefore appear at low levels in the environment.
They are defined as carrier-free submicron colloidal drug delivery systems with a mean particle size in the nanometer range.
Generally, saturation solubility is thought to be a function of temperature, but it is also based on other factors, such as crystalline structure and particle size, in regards to nanocrystals.
Instability problems of nanocrystalline structures derive from thermodynamic processes such as particle aggregation, amorphization, and bulk crystallization.
Particles at the nanoscopic scale feature a relative excess of Gibbs free energy, due to their higher surface area to volume ratio.
[34] Liposomes are spherical vesicles composed of synthetic or natural phospholipids that self-assemble in aqueous solution in sizes ranging from tens of nanometers to micrometers.
The molecular cargo is loaded through liposome formation in aqueous solution, solvent exchange mechanisms, or pH gradients methods.
The anthracycline drug doxorubicin is delivered with phospholipid-cholesterol liposomes to treat AIDS-related Kaposi sarcoma and multiple myeloma with high efficacy and low toxicity.
Other methods use aggregators such as leucine zippers or polymer-DNA amphiphiles to induce capsid formation and capture drug molecules.
It is also possible to chemically conjugate of drugs directly onto the reactive sites on the capsid surface, often involving the formation of amide bonds.
[41] Nanoparticle albumin-bound technology utilizes the protein albumin as a carrier for hydrophobic chemotherapy drugs through noncovalent binding.
Passive targeting depends on the fact that tumors have abnormally structured blood vessels that favor accumulation of relatively large macromolecules and nanoparticles.
This so-called enhanced permeability and retention effect (EPR)[42] allows the drug-carrier be transported specifically to the tumor cells.
Active targeting is, as the name suggests, much more specific and is achieved by taking advantage of receptor-ligand interactions at the surface of the cell membrane.
For example, the triblock copolymer of poly(ethylene glycol)-b-poly(3-aminopropyl-methacrylamide)-b-poly(N-isopropylacrylamide) (PEG-b-PAPMA-b-PNIPAm) can self-assemble to form micelles, possessing a core–shell–corona architecture above the lower critical solution temperature.
In one study, gold nanoparticles functionalized with double-stranded DNA encapsulated with drug molecules, were irradiated with NIR light.
Gold nanoparticles of sizes below 4-5 nm fit in DNA grooves which can interfere with transcription, gene regulation, replication, and other processes that rely on DNA-protein binding.
Lack of biodegradability for some nanoparticle chemistries can lead to accumulation in certain tissues, thus interfering with a wide range of biological processes.
