Synthesis and characterization of poly(3-hydroxybutyrate)/chitosan-graft poly (acrylic acid) conjugate hyaluronate for targeted delivery of methotrexate drug to colon cancer cells

Abstract

Anti-cancer medications that are delivered specifically to the tumor site possess greater efficacy with less negative effects on the body. So, the current research relies on a novel method for intercalating the anticancer medication methotrexate in poly(3-hydroxybutyrate)/chitosan-graft poly (acrylic acid) conjugated with sodium hyaluronate. The graft copolymers were synthesized through persulfate-initiated grafting of acrylic acid onto a binary mixture of various amounts of chitosan and poly(3-hydroxybutyrate) (2/1, 1/1 and 1/2, w/w) using microwave irradiation. The graft copolymer was conjugated with sodium hyaluronate for targeted delivery of methotrexate drug specifically to colon cancer cell lines (Caco-2). The graft copolymers were characterized by many physical techniques. The maximum drug loading efficiency was observed in case of the graft copolymer/hyaluronate rich in chitosan content 69.7 ± 2.7 % (4.65 mg/g) with a sustained release about 98.6 ± 1.12 %, at pH 7.4. The findings of severe cytotoxicity having a value of the IC50 of 11.7 μg/ml, a substantial proportion of apoptotic cells (67.88 %), and an elevated level of DNA breakage inside the treated Caco-2 cells verified the effective release of methotrexate from the loaded copolymer matrix. Besides, the high stability and biological activity of the released drug was exhibited through occurrence of greater increment of reactive oxygen species and effect on the extent of expression of genes connected to apoptosis and anti-oxidant enzymes within the treated cells. Ultimately, this system can be recommended as potent carrier for methotrexate administration to targeted cancerous cells in the colon.