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Drug Delivery

Drug Delivery - Poster Session C

Poster J6 - Modeling the effects of skin pigmentation on light transmittance during photodynamic therapy: implications for a novel drug targeting and delivery system

Friday, October 25, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Over 130,000 women were diagnosed with breast cancer in 2021. Photodynamic therapy (PDT) is an existing treatment that administers photosensitizers, followed by a specific wavelength of light, to produce high concentrations of reactive oxygen species (ROS) that cause cancer cell death. PDT is now used clinically to treat breast, skin, and head and neck cancers. PDT alone, however, is limited to specific depths of tissues and is used in conjunction with chemotherapy. Chemotherapy damages healthy tissues in addition to cancer, causing severe adverse side effects. By targeting therapeutics at the cancer site, the dosing of these therapeutics can be minimized, reducing damage to healthy tissues and improving treatment effectiveness. We aim to combine the existing PDT therapy with a novel drug targeting and delivery system. The excess production of ROS from PDT at the tumor will drive the crosslinking of acrylate polymers with one part of a chemistry click pair. The ROS from PDT will initially damage the tumor and then enable the targeting for a payload, which is conjugated to the other part of the click chemistry pair. The polymer net “catches” the payload, which is “released” by enzymatic digestion. In this research, we aim to confirm the compatibility of PDT with our novel system. One crucial step is modeling the effect of skin pigmentation on light transmittance, as light transmittance directly affects ROS generation and our system's efficacy across diverse populations. We hypothesize that darker skin models will lead to lower percentages of light transmittance.

Materials and

Methods:  We use agar as our model tissue, which allows for the inclusion of water-soluble photosensitizers, polymers, and therapeutics. Negrosin is included to introduce a light-absorbing agent, and intralipids are included to introduce a light-scattering agent. Both are necessary to emulate pigmentation. A 20%(v/v) intralipid stock solution was serially diluted with distilled water 1:2 until 12.5% (v/v). A similar process was performed with a stock solution of 5%(w/v) nigrosin to reach 0.3125%. Tissue mimics were created by heating up 2% agar to 90 °C and adding desired concentrations of intralipid and Nigrosin to produce mimics containing intralipid concentrations ranging from 0.125% to 2% and Nigrosin concentrations of 0.003125% to 0.05%. A 2% agar tissue mimic with no intralipid or Nigrosin was used as a control. Once tissue mimics had reached 90 °C, solutions were allowed to cool between 60-75 °C and then transferred to 6-well plates. Tissue mimics were allowed to set and cool completely at room temperature. Once completely set and cool, mimics were exposed to 660nm light. Transmitted light was measured by creating a specialized setup using Thorlabs Analog Handheld Laser Power Meter (PM100A), LED Driver (LEDD1B), SM1-Threaded 30mm Cage Plate (CP02), 660 nm, 940 mW (Min) Mounted LED, 1200 mA (M660L4), and 400-1100nm Photodiode Power Sensor (S120C). Tissue mimics of each variation were completed in triplicate. The percent transmittance of each tissue mimic was calculated, and averages were recorded and displayed in a heat map.

Results, Conclusions, and Discussions: Figure 1 displays a heat map of percent light transmission as a function of intralipid and Nigrosin concentration. Tissue mimics resulted in transmittance percentages ranging from 0-83%. The control (2% agar alone) resulted in decreased transmission to 82.02%. Increasing intralipid and Nigrosin concentrations resulted in lower percentages of light transmittance. No light was transmitted through tissue mimics containing 0.05% w/v Nigrosin with either 0.5%, 1%, or 2% of intralipid. These results indicate that darker skin models result in lower transmittance of light. This would directly impact the efficacy of the “catch and release” delivery system. Darker skin models will be unable to transmit light through the skin and, therefore, will not generate adequate ROS for our polymer to crosslink and generate a net. A subset of tissue mimics were within the transmittance range of human skin for 660nm light (5%-20%). These mimics will be used to characterize the generation of ROS from Chlorin e6, a common photosensitizer, and confirm polymer net formation. Employing this range of models will help ensure equity in our treatment.

Acknowledgements (Optional):  We want to acknowledge all RISE at Rutgers staff and administration and Rutgers University Cellular Bioengineering REU for support in the project. This research was also funded by the National Science Foundation (EEC-1950509 and EEC-2349225), the New Jersey Health Foundation, and the New Jersey Commission on Cancer Research (COCR24PRF012).