Abstract
There is a need to formulate oral cetuximab (CTX) for targeting colorectal cancer, which is reported to express somatostatin receptors (SSTRs). Therefore, coating CTX with a somatostatin analogue such as octreotide (OCT) is beneficial. Alginate was used to coat CTX to facilitate delivery to the gastrointestinal tract (GIT). This study aimed to deliver CTX conjugated with OCT in the form of microparticles as a GIT-targeted SSTR therapy. Both CTX and OCT were conjugated using a solvent evaporation method and the conjugated CTX-OCT was then loaded onto Ca-alginate-beads (CTX-OCT-Alg), which were characterized for drug interactions using differential scanning calorimetry (DSC), and Fourier transform infrared spectra (FTIR). Moreover, the morphology of formulated beads was examined using a scanning electron microscope (SEM). The drug content and release profile were studied using UV spectroscopy. Finally, in vitro cytotoxicity of all compounds was evaluated. The results showed homogenous conjugated CTX-OCT with a diameter of 0.4 mm. DSC showed a delay in the OCT peak that appeared after 200 °C due to small polymer interaction that shifted the OCT peak. Moreover, FTIR showed no prominent interaction. SEM showed clear empty cavities in the plain Ca-alginate-beads, while CTX-OCT-Alg showed occupied beads without cavities. CTX-OCT-Alg had a negligible release in 0.1 N HCl, while the CTX-OCT was completely released after 300 min in phosphate buffer pH 7.4. All formulations showed good antiproliferative activity compared with free drugs. The formulated CTX-OCT-Alg are a promising platform for targeting colorectal cancer through GIT.
Highlights
Www.nature.com/scientificreports shown proliferative inhibition of colon cancer cell lines[11]
Targeted therapy is a good method for the management of colorectal cancer through the use of “epidermal growth factor receptor inhibitors” (EGFR), such as CTX, which is linked to oral squamous cell carcinoma patient survival[16]
OCT is a somatostatin analogue commonly used as an anti-cancer agent that targets SSTRs in the gastrointestinal tract (GIT) that are expressed in colon cancer
Summary
Www.nature.com/scientificreports shown proliferative inhibition of colon cancer cell lines[11]. Lelle et al presented a modern approach to drug-carrier conjugate in a site-specific manner providing excellent versatility and allowing stimulated release within cancer cells. They developed doxorubicin-octreotide bioconjugate for overexpressed SSTRs in tumor cells, where the first cleavable disulphide-intercalating connector was the binding between the two elements. Ca-alginate-beads delivered an anti-cancer agent such as etoposide or that avoided the systemic adverse effects of chemotherapeutic agents and provided targeted, controlled treatment with reduced cytotoxicity[26]. This study aimed to provide oral colonic targeted therapy using OCT-conjugated CTX to avoid systemic side effects. CTX was conjugated with OCT in Ca-alginate-beads for targeting SSTRs expressed in colorectal cancer. The final formulation was characterized by particle size, DSC, FTIR, in vitro release of the formulated CTX-OCT-Alg at phosphate buffer pH 7.4, and cytotoxic activity
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