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Drug Delivery

With optimized physicochemical and biological properties, nanotechnology becomes a potential method of replacing traditional medicines and the next generation tools for drug delivery applications.

Advantages of Nanoparticles in Drug Delivery

Compared to the traditional forms of drugs, nanoparticles delivery systems offer many advantages. Nanoparticles can be water-soluble and taken up by cells easily, so they can be successfully used as delivery tools for currently bioactive compounds with low solubility. Another major advantage that nanotechnology offers is targeted drug delivery to the site of disease. Drugs are usually absorbed or conjugated onto the surface of a particle, encapsulated inside the polymer and lipid, or dissolved within the particle matrix to form the nanoparticle drug delivery system. Thus, drugs can be protected from a critical environment, and their unfavorable biopharmaceutical properties can be replaced by the desired properties of nanoparticles.

Drug Delivery

Application

  • Cancer Drug Delivery

Advanced tumors are characterized by several unique features, such as leaky vasculature, compromised lymphatic drainage, and an acidic microenvironment. Nanoparticles take advantage of these characteristics and achieve targeted chemotherapeutic drug delivery.

Due to tumor tissues’ leaky vasculature, circulating nanoparticles can be accumulated more in the tumor tissues than in normal tissues. Meanwhile, tumor tissues’ drained lymphatic system impedes nanoparticles excretion, resulting in an enhanced nanoparticles accumulation in tumor tissues. This effect is named enhanced permeability and retention (EPR) effect and has been widely applied in the design of nanoparticle-based chemotherapeutic drug delivery systems.

Another approach of realizing targeted drug delivery is utilizing targeting ligands, which is also named as ‘active targeting’. By conjugating targeting ligands to nanoparticles, therapeutic agents can be selectively delivered and accumulated at diseased sites through ligand-receptor interactions.

Several nanoparticle-based drugs have been commercialized and readily available in the market. Doxil is the first nanoparticle-based drug received FDA approval in 1995. Followed by which, various kinds of nanoparticles have been studies for targeted chemotherapeutic drug delivery and several of them also got FDA approval. Numbers of nanoparticle-based drug research were also established and many of them reached clinical trial stages.

Among these applications of nanoparticles in targeted chemotherapeutic drug delivery, nanoparticles are objects sized between 10 and 100 nm that work as a whole unit in terms of transport and properties. Other properties, such as negative surface charge and high drug loading efficiency, are also defined as the optimum nanoparticle for chemotherapeutic drug delivery.

Schematic illustration of enhanced permeability and retention (EPR) effect induced nanoparticle-based targeted delivery.Figure 1. Schematic illustration of enhanced permeability and retention (EPR) effect induced nanoparticle-based targeted delivery.

  • Oral Drug Delivery

Oral delivery is the most widely used and most readily accepted method of drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal tract challenging. Numbers of barriers, such as the acidic gastric environment and the continuous secretion of mucus, must be overcome before a therapeutic is absorbed and enters the bloodstream.

Nanoparticle drug carriers can shield drugs from degradation and deliver them to intended sites within the gastrointestinal tract and enable more efficient and sustained drug delivery. The most well-known application of nanoparticles in oral delivery is the oral administration of insulin. Studies encapsulate insulin into nanoparticles, mainly polymeric nanoparticles, and used them to overcome the gastrointestinal tract barriers for the effective delivery of insulin through oral administration. Several insulin-encapsulated nanoparticles are in the progress of clinical trials.

  • Brain Drug Delivery

The blood-brain barrier (BBB) is a highly complex structure that protects the central nervous system. The BBB limits the movement of small molecules and macromolecules from the blood to the brain, protecting the central nervous system from injuries and diseases. However, the BBB also significantly precludes the delivery of drugs to the brain, resulting in a significant decline in therapeutic efficacy. As a consequence, several strategies have been developed to enhance the delivery of drugs across the BBB.

Nanoparticles have been proposed as an intriguing tool to solve the unmet problem of drug transporting across the BBB. The possibility of nanoparticle multifunctionalization enables the coupled loading of therapeutic agents with targeting ligands and promotes at the same time either their targeting of the BBB or the enhancement of its crossing. Meanwhile, nanoparticles confer the feasibility of incorporating both hydrophilic and hydrophobic pharmaceuticals and the ability to be administered by a variety of routes.

Liposomes, dendrimers and polymer-based nanoparticles have been demonstrated as feasible carriers for enhanced brain drug delivery. The applications of other particles, such as gold and silver nanoparticles, are also under investigation.

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