Cetuximab Conjugated with Octreotide and Entrapped Calcium Alginate-beads for Targeting Somatostatin Receptors.
Administration, Oral
Alginates
Antineoplastic Agents, Immunological
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cetuximab
/ administration & dosage
Chemical Phenomena
Colorectal Neoplasms
/ metabolism
Dosage Forms
Drug Compounding
/ methods
Drug Delivery Systems
Drug Liberation
Gastrointestinal Tract
/ metabolism
Humans
Molecular Targeted Therapy
Octreotide
Receptors, Somatostatin
/ metabolism
Somatostatin
/ analogs & derivatives
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 03 2020
13 03 2020
Historique:
received:
26
09
2019
accepted:
29
02
2020
entrez:
15
3
2020
pubmed:
15
3
2020
medline:
15
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32170176
doi: 10.1038/s41598-020-61605-y
pii: 10.1038/s41598-020-61605-y
pmc: PMC7069942
doi:
Substances chimiques
Alginates
0
Antineoplastic Agents, Immunological
0
Dosage Forms
0
Receptors, Somatostatin
0
Somatostatin
51110-01-1
Cetuximab
PQX0D8J21J
Octreotide
RWM8CCW8GP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4736Références
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