(F-213) Development and Characterization of a Novel Interpenetrating Polymer Network Hydrogel for Local Drug Delivery

Introduction:: The incidence rate of central nervous system (CNS) cancers in pediatric patients is 48.6 per million while five-year survival rate is 74% [1]. Medulloblastoma accounts for 20% of pediatric CNS tumors. Mostly used treatment methods for pediatric brain tumors are surgery, radiation therapy, and chemotherapy. Although these treatment methods help to heal patients, they have disadvantages such as i) risky operations, ii) weaken the immune system, iii) systemic toxicity, iv) low bioavailability at the tumor site, v) uncontrolled drug release. In this study, it is hypothesized that synthesizing an injectable, starch based, and interpenetrating polymer network (IPN) hydrogel loaded with doxorubicin will increase the bioactivity at tumor site, provide controllable drug release and decrease systemic toxicity.


Materials and Methods:: Starch components amylopectin (AMY) and amylose (SS) used to create single network and IPN hydrogels. Dimethyl sulfoxide (DMSO) used as a solvent. Microwave assisted synthesis (MAS) method conducted to obtain hydrogels. Different compositions of IPN hydrogel characterized by using Fourier transform infrared spectroscopy (FTIR) and rheology to confirm IPN structure in the hydrogels. Drug release studies will be conducted by using high performance liquid chromatography (HPLC). The relationship between IPN structure and drug release rate will be investigated. The most suitable IPN structure and optimum drug release model will be chosen as a drug carrier for local injection to the tumor site.


Results, Conclusions, and Discussions:: Results and Discussion
Phase separation occurs due to difference of the molecular weights of the starch components. Therefore, AMY chains gelatinize and create network 1 and SS chains gelatinize and crate network 2. While this gelation process is taking place, these networks entangle each other physically. These physical entanglements among the networks lead to the formation of IPN. In Figure 1, SS has the highest storage modulus while AMY has the lowest storage modulus. The composite of AMY and SS components show a storage modulus between the other samples. IPN structures show the properties of the materials they are composed of. It can be interpreted that the composite hydrogel got affected by the characteristics of both networks and revealed an intermediate storage modulus. Therefore, this data provides a clue that this composite hydrogel has an IPN structure.

A change of the peak intensity at the hydrogen bond region is observed when physical bonding occurs in the sample. More intense peak is observed in the single networked sample due to uncross linked hydroxyl groups. Low intensity peak at the composite sample indicates that these hydroxyl groups are bonded to create physical entanglements. Based on this, AMY hydrogel displays more intense peak than the composite hydrogel due to uncross linked hydroxyl bonds. Low intensity of the peak indicates that physical bonding is occurred between AMY and SS networks so composite hydrogel can be confirmed as an IPN.

Conclusion
According to rheological data, highest hydrogel concentration with 1:1 AMY/SS ratio showed an IPN structure. As more hydrogels are synthesized and more data are obtained, a more precise examination method will be developed based on experience and data.


Acknowledgements (Optional): :

References (Optional): : [1] Rebecca L Siegel, Kimberly D Miller, Nikita Sandeep Wagle, and Ahmedin Jemal. Cancer statistics, 2023. CA: a cancer journal for clinicians, 73(1):17–48, 2023.