Encapsulating or embedding drugs into polymer carriers can provide many advantages over free drug delivery. For example, encapsulating toxic drugs (such as chemotherapy agents) can shield the healthy tissue from the deleterious effects, whereas encapsulating fragile drugs (such as DNA or peptides) can prevent their degradation and inactivation by the immune system.

Layer-by-layer (LbL) assembly of polymers results in a thin multilayered film into which drugs can be trapped or anchored. The films are assembled on the surface of macroscopic templates (such as stents) or on the surface of micro- or nanoparticles for intravenous delivery. To create the films, the template is dipped alternately into polymer solutions that typically interact with one another by electrostatic, hydrogen or covalent bonding. The process is repeated to create a multilayered polymer film on the surface of the template. If particles are used as templates, they may be dissolved to create free-standing nano- and microcapsules. LbL assembly is a highly versatile process and drug carriers can be created to diverse specifications simply by changing the polymers or template used in the assembly process. A new review by Becker et al. describes the current status of the use of LbL-assembled materials in therapeutic delivery.

There are many advantages to the use of LbL assembled materials. Multilayered films (especially in capsule form) have a high payload capacity for drugs and they can also encapsulate several different drugs within the same film or carrier. Additionally, drugs with varied properties can be encapsulated, from small hydrophobic molecules to large charged biomolecules. The films can be made ‘intelligent’ by assembling the films from responsive polymers. These responsive films can be designed to release their drugs in response to changes in pH and temperature or in the presence of specific enzymes or small molecules. Additionally, they may be designed to degrade slowly to release a continuous dose of a drug over a period of days or weeks. Some of the drug carriers currently being developed have potential applications in the treatment of cancer, or the development of vaccines against HIV.



FIGURE: 3D reconstructed confocal laser scanning microscopy images of microcapsules (green) filled with DNA (red) (left) and a macrophage cell (membrane outlined in purple) filled with microcapsules (green) (right).

The key challenges facing researchers developing LbL-assembled materials for therapeutic delivery are in understanding how these materials interact with biological environments. The behavior of these materials in simulated laboratory environments is now fairly well understood; however, information in complex biological systems is still sparse. Although there are studies that seek to understand how the surface chemistry, mechanical properties, size and shape affects particle interaction with cells, there are few guiding principles that can be applied to all systems. This information has implications beyond the LbL community and into the larger biomaterials science community. It is not only important for the rational design of carriers, but also for understanding their potential toxicity in the body.

In the future we can expect to see multifunctional LbL-assembled drug carriers that encompass all of the attributes discussed above in a single system and an improved understanding of how these materials behave in biological systems.

A. Becker et al., Small