text: Pullulan is used as a bioconjugate platform in order to enhance the delivery of chemotherapeutics. Pullulan derivatives can be created in order to specifically target cancer cells. In terms of cancer therapeutics, pullulan can be used to encapsulate hydrophobic cancer therapeutics through self assembled micelles, can be linked to drugs in the form of a bioconjugate, and can be utilized for its pH responsive nature. Cancer drugs that have been used with pullulan include doxorubicin, paclitaxel, epirubicin, mitoxantrone, and 10-hydroxycamptothecin. 
  Pullulan derivatives can be folated in order to take advantage of the higher density of folate receptors on cancer cells. Doxorubicin has been loaded into pullulan micelles and folated micelles for targeted delivery to cancer cells through folate mediated endocytosis. The use of folated pullulan nanoparticles shows lower toxicity and higher levels of drug accumulation within the cancer cells. The pH sensitivity of pullulan also makes pullulan a good candidate for chemotherapeutic delivery, as the pullulan can be altered by the acidic environment of the tumor to provide targeted release. 
  Pullulan nanoparticles have also been used to deliver paclitaxel and proved to be stable under different environmental conditions. Curcumin pullulan derivatives have a great effect in targeting hepatocarcinoma cells, as the pullulan increases the ability of curcumin to solubilize, and therefore allows for the cells to properly uptake the curcumin. Pullulan micelles can also be used to deliver genes, such as p53, in order to suppress tumor development. The pullulan protects the RNA or DNA from degradation from enzymes within the body, which enables the ability of gene therapy for treatment of cancer. The addition of ascorbic acid to pullulan bioconjugates has demonstrated antimetastic properties, which can improve cation modified pullulan derivatives. There are many factors that make pullulan a suitable drug delivery platform for cancer therapeutics. Some of these factors include the chemical modifications, the pH responsiveness, as well as the ability for the pullulan to form self-assembled micelles that can protect the therapeutics from the immune system.
  In vitro research has been conducted that synthesized pullulan acetate nanoparticles altered with folate and then loaded with epirubicin.  This study showed that the use of folate modification to pullulan increased the cytotoxicity of the drug as well as released the drug at a faster rate than unfolated pullulan acetate. Another pullulan folated system was researched, where pullulan gold nanoparticles were folated and encapsulated doxorubicin. The pullulan gold nanoparticle provided pH controlled release of the doxorubicin and demonstrated lower toxicity to non cancer cells than doxorubicin without a carrier platform. CHP systems have been developed to deliver protein vaccines and have shown success in generating different degrees of immune responses mostly with CD4 T cells. Biotinylated pullulan acetate (BPA) have been created as they have vitamin H functionality, which helps increase the level of interaction with cancer cells. The drawback with vitamin H is that increasing the vitamin H increases the interaction of the nanoparticles with cancer cells, but also lowers the concentration of the drug in the nanoparticle due to the altered hydrophobicity. Modifications to pullulan can be made to enhance the controlled release of drugs, such as pullulan-g-poly(L-lactide) due to the water insoluble nature of the polymeric component.  Doxorubicin has been conjugated to pullulan through hydrazone bonds, but was shown to have lower cytotoxic activity than doxorubicin without a delivery platform.