14.4.3  Poke and Release

Instead of inserting a microneedle, depositing the drug and removing the microneedle, the microneedle itself could be left behind in the tissue. This approach, the poke- and-release approach, involves loading a drug formulation within a microneedle and leaving the microneedle in the tissue as it releases the loaded drug formulation into the tissue. These microneedles are usually made of biodegradable polymers or sugars that encapsulate a drug, and as the polymer breaks down or sugar dissolves it releases the active agent within the tissue. The added benefit of this approach is that the polymer could control the release of the molecule that is encapsulated within the microneedle and provide sustained release. This would extend the time the drug is within the eye and allow for less frequent administration.

Microneedles made of biodegradable polymers have been shown to successfully insert and deliver molecules into the skin. Park et al. showed that an array of polymer microneedles can be fabricated using a micromolding technique. Mechanical testing of these microneedles made of biodegradable polylactic and polyglycolic acid copolymers (PLGA) were strong enough to insert into the skin and increase skin permeability of calcein and BSA (Park et al. 2005). Microneedles encapsulating small molecules and proteins within PLGA have also been shown to deliver their payload over extended periods of times. As a result, controlled drug delivery is achievable with the microneedles for periods of hours to months depending on the formulation and encapsulation methods (Park et al. 2006). It has also been shown that microneedles made of CMC could be designed to insert and degrade in the skin to deliver a drug. Figure 14.17h shows a polymer microneedle array made of CMC. A micromolding and encapsulating method was developed to deliver a model protein, lysozyme into pig cadevar skin. The enzymatic activity of lysozyme after 2 months within the microneedle array was 96% of the initial activity indicating the processing conditions and microneedle formulation were benign to the enzyme. By encapsulating drug into the backing layer in addition to the microneedle shaft, the microneedles and patch could be used to provide sustained drug delivery (Lee et al. 2008). Although these microneedles have not been inserted or tested in eye tissues, they could conceivably be inserted in a similar fashion for ocular drug delivery.

14.4.4  Poke and Flow

The poke-and-flow approach to using a microneedle is analogous to the hypodermic needle. A hollow microneedle is inserted within a tissue and a liquid formulation can be injected through the hollow cannula in the microneedle for delivery within a tissue at depths of less than 1 mm. Hollow microneedles provide unique capabilities such as being able to inject formulations and to immediately spread the injected formulation within tissues. This is in contrast to other microneedle designs and approaches that deposit the drug only locally to the insertion site. This is advantageous from two