Abstract
Colorectal cancer (CRC) is one of the most malignant and fatal cancers worldwide. Although cytoreductive surgery combined with chemotherapy is considered a promising therapy, peritoneal adhesion causes further complications after surgery. In this study, oxaliplatin-loaded Poly-(d,l-lactide-co-glycolide) (PLGA) microparticles were prepared using a double emulsion method and loaded into hyaluronic acid (HA)- and carboxymethyl cellulose sodium (CMCNa)-based cross-linked (HC) hydrogels. From characterization and evaluation study PLGA microparticles showed smaller particle size with higher entrapment efficiency, approximately 1100.4 ± 257.7 nm and 77.9 ± 2.8%, respectively. In addition, microparticle-loaded hydrogels showed more sustained drug release compared to the unloaded microparticles. Moreover, in an in vivo pharmacokinetic study after intraperitoneal administration in rats, a significant improvement in the bioavailability and the mean residence time of the microparticle-loaded hydrogels was observed. In HC21 hydrogels, AUC0–48h, Cmax, and Tmax were 16012.12 ± 188.75 ng·h/mL, 528.75 ± 144.50 ng/mL, and 1.5 h, respectively. Furthermore, experimental observation revealed that the hydrogel samples effectively protected injured tissues from peritoneal adhesion. Therefore, the results of the current pharmacokinetic study together with our previous report of the in vivo anti-adhesion efficacy of HC hydrogels demonstrated that the PLGA microparticle-loaded hydrogels offer novel therapeutic strategy for CRC treatment.
Highlights
Colorectal cancer (CRC) is one of the most malignant cancers worldwide
As cytoreductive surgery and intraperitoneal chemotherapy are closely related to the completeness of cytoreduction, problems associated with cytoreductive surgery are still a big challenge in medical science
Oxaliplatin was a gift from Boryung Pharm (Ansan, Korea)
Summary
Colorectal cancer (CRC) is one of the most malignant cancers worldwide. the incidence of CRC is low, the number of new cases that are malignant and fatal is still the highest among both men and women. Oxaliplatin (Figure 1) is a third-generation, platinum-based, systemic chemotherapeutic agent for CRC [7], and it is expected to be effective in peritoneal carcinomatosis. It is currently being used as a part of the standard chemotherapy regimen, FOLFOX (oxaliplatin with 5-fluorouracil and leucovorin) [8], for the clinical treatment of metastatic CRC [9]. Alternative reports of paclitaxel-loaded PLGA microparticles have been evaluated for cancer therapy These models revealed protection of the therapeutic payload from premature burst release, Pharmaceutics a2n01d9e,n1a1b, lxe the sustained release of paclitaxel [16,17]. MaterialshyadnrodgeMls seigtnhifiocdanstly prevented intraperitoneal adhesion and offered the highest anti-adhesion barrier
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