From Bench to Bedside—An Example of an In Situ Hydrogel in In Vivo Applications - In-Situ Gelling Polymers: For Biomedical Applications - page 213

intracranial and spinal cord and the pancreas [ 4 , 7 , 8 , 11 , 12 ]. The focus of the
studies in rats and dogs was to determine the no adverse event level (NOAEL) and
the maximum tolerated dose in normal tissues. The outcome of these local toler-
ability studies established that the dose-limiting toxicities (DLTs) were local in
nature, so the need to consider systemic toxicity was eliminated while considering
the starting dose. These studies propelled the research towards the clinical dose
escalation studies of Oncogel as an anti-cancer agent in humans.
2.2 Tissue Distribution Studies
After determining the DLT, it is necessary to carefully study the distribution of
Paclitaxel following release from the Oncogel, in order to manage the potential addi-
tive toxicity and avoid further complications in the patient. An ADME (adsorption,
distribution, metabolism, and excretion) study of paclitaxel was performed follow-
ing OncoGel's intralesional administration to the MDA-MB-231 breast tumor xeno-
graft in mice. The study examined the distribution of radioactively labeled paclitaxel
over a span of 42 days. Paclitaxel was reported to be localized within the tumor
with minimal levels (<0.2 %) detected in the blood, tissues or urine. The elimina-
tion route was via feces, similar to the paclitaxel elimination following systemic
administration. The distribution and concentration of paclitaxel in the surrounding
tissues, derived from these studies are essential criteria to be considered when select-
ing Oncogel injection sites and its placement into a tumor cavity after a surgery [ 5 ].
3 Development of Oncogel™ as a Potential Cancer
Therapeutic Drug
After acquiring the preliminary information related to the distribution and safety
of Oncogel™, it was necessary to evaluate its efficacy in animal models. Novel
drug delivery methods were explored for efficient delivery of Oncogel™ to the
tumor site. The feasibility of combining Oncogel™ with chemotherapy, radiation
therapy and surgeries was also explored.
3.1 Rat Model Studies
3.1.1 Spinal Cord
Spinal column is the most common site of skeletal osseous metastases, with lung
and breast lesions being the primary ones to metastasize [ 7 ]. As there are advances
made in the diagnosis and treatment of the primary disease, the life span of a
patient generally increases causing an increase in the frequency of treatment for
symptomatic distant metastases.