Enhancing Clinical Therapy for wet Age-related Macular Degeneration (wetAMD)

ABSTRACTThe wet form of age related macular degenerationAMDaccounts forof all AMD related blindness and affectsmillion people withnew cases each year in the USMinimally invasive and selective drug delivery to the eye still remains an open challengethe current standard of care involves delivery of antivascular endothelial growth factoranti VEGFdrugs via intraocular injectionFor patients refractory to antiVEGF drugsphotodynamic therapyPDTis the standard of careClinical efficacy of PDT depends on significant accumulation of the photosensitizerPSat the choroid neovasculatureCNVavailability of oxygen near the PSand effective dosing of the drug light combinationOur new platform for delivery and imaging of PSentitled the Photodynamic therapy NanoDropletPtNDwill enhance all three of these areasraising PDTandapos s therapeutic index and enabling PDT to become a frontline clinical wet AMD therapyPtND comprises a core of oxygen rich liquid perfluorocarbonPFCcontaining indocyanine greenICGdye stabilized by a lipid shell which both houses the photosensitizerPSand provides binding sites for conjugating choroid targeting moietiesFollowing intravitreal injectionPtND will transcytose through the retinal pigment epitheliumbind with choroid neovesselsand undergo receptor mediated endocytosisInterestinglythe ICG dye is used to trigger a liquid to gas phase change of the PFC which serves two purposesit delivers PS and additional Oto the cell cytosol andthe vaporization event creates a giant acoustic transient which can be used in combined photoacoustic and ultrasoundPAUSimaging to visualize the distribution of drug delivery at the CNVFrom the rich spatial information received by PAUS imaging of the drug distributionlight intensity and duration dosimetry for the choroid region can be calculatedThis personalized dosimetry will ensure patients receive the correct dose for their disease burdenThe promise of PDT to provide localized therapy with minimal residual damage or systemic side effects is remarkableThe proposed PtND platform is poised to enhance delivery of PS to CNVincrease efficacy of PDT through companion Odeliveryand ultimately deliver a personalized patient specific dose enabled by PAUS imagingThe overall goal of our project is to demonstrate that PtND can raise the therapeutic index of PDT in vivoleading to a decrease in required treatments for wet AMDand ultimately replace the need for anti VEGF drugs which carry a risk of systemic side effectsOverall we are excited to develop this nanoplatform for PDT that will remove the roadblocks to widespread use of this important clinical treatment NARRATIVEThe wet form of AMD accounts forof all AMD related blindness and affectsmillion people withnew cases each year in the USFor patients refractory to anti angiogenesis drugsphotodynamic therapyPDTis the standard of careClinical efficacy of PDT depends on significant accumulation of the photosensitizerPSat the choroid neovasculatureCNVavailability of oxygen near the PSand effective dosing of the drug light combinationOur new platform for delivery and imaging of PSentitled the Photodynamic therapy NanoDropletPtNDwill enhance all three of these areasraising PDTandapos s therapeutic index and enabling PDT to become a frontline clinical wet AMD therapy