Current approaches for cancer treatment or treatment of other disorders include combinations of local therapies, such as surgery, radiation therapy, and systemic delivery of chemotherapeutic agents. The therapeutic success of any contained tumor treatment is directly reflected in the level of therapeutic agent or chemical dose which can be delivered yet minimize toxicity to normal tissue and toxic side effects to the patient. The combination of radiotherapy and chemotherapy provides the best clinical efficacy (i.e. increased median and long term survival), but the increased toxicity from this multimodality approach limits its application and increases the need for additional supportive measures. This inherent toxicity can be significantly reduced by achieving better control of delivery to the tumor or diseased tissue.
Despite advancements that provide localized radiation and increased delivery of chemotherapeutic and other drugs to target areas in the body, sufficient drug release at the target site remains a problem.
This innovation involves both methods and compositions for the controlled release of a drug or agent from a liposome using either light or radiation. The unique compositions are set up for the triggered activation of liposome dissolution and release of drugs of interest at the site of activation by light or radiation. This is accomplished through unique compositions comprising liposomes having a lipid layer, wherein which an agent, and an enzyme capable of releasing the agent from the liposome. The compositions include the presence of an enzyme activator all encapsulated in a molecular cage that is sensitive to and activated by radiation. Upon radiation exposure, the cage releases the activator, which triggers activation of enzymatic activity and hydrolysis of the lipidic component of the lipid bilayer, thus increasing permeability and releasing the drug. In addition, yet another aspect of this invention includes the methods of delivering an agent to a target in a patient.
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09-07 UAMS Borrelli + 09-17 UAF Salamo, et al