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Introduction: Globally, ovarian cancer (OC) ranks as the most common cancer among gynecological malignancies. Recent research highlights the critical importance of the perioperative phase in deterring tumor recurrence. During this time, chemotherapy is the predominant treatment method, and numerous drugs have been developed for this purpose [1,2]. However, a major challenge is sustaining the long-term presence of these drugs at the surgical site after the operation to prevent relapse. Implementing such targeted strategies could significantly diminish the residual tumor cells and/or avert micro-metastases during the post-surgical phase. Hence, this study hypothesizes the development of a tissue adhesive hydrogel targeting OC recurring cells, which is encapsulated with drug-loaded carriers that can be used in the resection site to diminish the residual cancer cells post-surgery.
Methods: (1) Development of novel tissue adhesive hydrogel. (2) Preparation of potential drug carriers. (4) Encapsulation of potential carriers with the PARPi (Poly ADP Ribose Polymerase inhibitors) drug. (5) Load the drug-loaded carrier into the tissue adhesive hydrogel and test it in vitro and in vivo.
Results and Discussion. The project is in its mid-phase, and the novel hydrogel, which will serve as the drug delivery platform, is being synthesized first. Different trials and errors were carried out with different natural biomaterials and tuned to crosslink and form a stable hydrogel system at 37 °C without requiring external crosslinkers like UV crosslinking. The following are the different hydrogels stably crosslinked at 37 °C;
Biomaterial Combinations,
The combination IN+PG (1:1) was chosen as the base hydrogel material for this project because it is unmodified, requires no chemical alteration, retains natural bioactivity, supports cell adhesion and proliferation, is cost-effective, and involves simple processing. It also demonstrates proven biocompatibility and low immunogenicity. This base hydrogel was designated as G+OI and was subsequently modified by incorporating additional biomaterials to form G+OI+PGS and G+OI+PGS+BC, aiming to enhance its properties further.
As seen in the results above, A, B, C, D, and E are the Milli-Q water (positive control), phosphate-buffered saline (negative control), hydrogel G+OI, hydrogel G+OI+PGS, and hydrogel G+OI+PGS+BC, respectively. All three hydrogel systems have very few hemolysis percentages, indicating that these hydrogels are highly compatible with body fluid. Also, the hydrogel G+OI+PGS+BC provides a better antioxidant property as seen in Figure H above.
Further, the hydrogels were optimized again to obtain a hydrogel system that will crosslink in a few seconds and have single-layer adhesion.
Fortunately, after many trials of different combinations, the hydrogel was successfully developed to crosslink in seconds and have the property of single-layer adhesion, as seen in figures F and H.
Currently, the newly developed hydrogel has been characterized. Upon completion of this phase, the potential drug carriers will be developed, and PARPi drugs will be loaded into these drug carriers, which will be encapsulated into the hydrogel system to form novel Exos@gel.
Conclusion. A novel tissue adhesive hydrogel encapsulated with PARPi drugs to target the post OC resection to reduce or eliminate the recurrence of OC will be developed upon completion of this project.
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