text: The ocular space is a difficult area to deliver drugs into and therefore special drug delivery considerations need to be taken into account. Intravitreal injections are a common method of delivery drugs to the eye. Pullulan systems can be utilized in intravitreal injections in order to develop drugs that are long lasting and therefore require less frequent injections. One study looked at different chemical linkers to pullulan to test efficacy of said linkers in extending the release of rhodamine B (RhB). This study used ether (Pull-Et-RhB), hydrazone (Pull-Hy-RhB), and ester (Pull-Es-RhB) linkers to generate pullulan bioconjugates. Ex vivo modeling of the drug release indicated that the drug diffuses slower in the vitreous humor than in water. The ether bond was stable at differing pH, while the hydrazone and ester bond released the drug faster in more acidic pH, that reflected the pH of endosomes. The Pull-Hy-RhB demonstrated that this drug delivery system was capable of delivering the drug to the retina through testing of the blood in the vessels of the retina. 
  Further studies have investigated the creation and efficacy of pullulan-dexamethasone bioconjugates for intravitreal injections. The study synthesized self-assembling pullulan nanoparticles with dexamethasone attached through hydrazone bonds.  This study reiterated that the drug release was fast in acidic pH that mimicked the pH of lysosomes. The variation in drug release was that at the pH of the vitreous humor the drug took two weeks to release half of the drug, while took only two days, when in a lysosomal pH. Pharmacokinetic analysis was performed on this bioconjugate system and revealed that dexamethasone was released in the vitreous humor and that it remained for sixteen days and that a substantial amount of the bioconjugate left the vitreous humor intact. Overall the studies regarding pullulan bioconjugates for the application in intravitreal injections demonstrate that pullulan can provide sustained release as well as allow the drug to reach the retina.