3.4.4. Clinical Trials Implementing Hyaluronic Acid-Based Nanoparticles

Primary studies in cell cultures and animal trials have shown promising results of HA-based nanoparticle efficiency in anticancer therapy. Some of these compounds have already been tested in Phase 2 or Phase 3 clinical trials with positive outcomes regarding efficiency and safety. A phase 2 trial tested HA-irinotecan plus cetuximab in 45 patients with KRAS wild-type metastatic colon cancer to examine the compound's safety and efficacy. However, the results of the study have not yet been announced [198]. Another

Inorganic

phase 2 study involving 39 patients with extensive-stage SCLC indicates that HA-irinotecan treatment provides survival benefits for patients bearing CD44 positive tumors [199].

Furthermore, phase 1 and 2 clinical trials utilizing HA-cisplatin nanoconjugates (HA-Pt) in dogs with naturally occurring anal sac carcinoma, oral squamous cell carcinoma, oral melanoma, nasal carcinoma, or digital squamous cell carcinoma have been conducted. The obtained results demonstrated the beneficial effects of HA-Pt drug formulations for the treatment of canine squamous cell carcinomas. Moreover, nephrotoxicity, a serious side-effect of Pt therapy, was not evident in any canine subject. Notably, canine oral SCC's similarity to human HNSCC regarding progression and drug response gives essential information for developing human treatments [200]. Examples of HA-based nanoparticle types tested in different cancer models are shown in Table 2.


**Table 2.** Types of HA-based nanoparticles tested in different cancer models.
