Alginate Microsphere Encapsulation of Drug-Loaded Nanoparticles: A Novel Strategy for Intraperitoneal Drug Delivery

Abstract

Alginate hydrogels have been broadly investigated for use in medical applications due to their biocompatibility and the possibility to encapsulate cells, proteins, and drugs. In the treatment of peritoneal metastasis, rapid drug clearance from the peritoneal cavity is a major challenge. Aiming to delay drug absorption and reduce toxic side effects, cabazitaxel (CAB)-loaded poly(alkyl cyanoacrylate) (PACA) nanoparticles were encapsulated in alginate microspheres. The PACAlg alginate microspheres were synthesized by electrostatic droplet generation and the physicochemical properties, stability, drug release kinetics, and mesothelial cytotoxicity were analyzed before biodistribution and therapeutic efficacy were studied in mice. The 450 µm microspheres were stable at in vivo conditions for at least 21 days after intraperitoneal implantation in mice, and distributed evenly throughout the peritoneal cavity without aggregation or adhesion. The nanoparticles were stably retained in the alginate microspheres, and nanoparticle toxicity to mesothelial cells was reduced, while the therapeutic efficacy of free CAB was maintained or improved in vivo. Altogether, this work presents the alginate encapsulation of drug-loaded nanoparticles as a promising novel strategy for the treatment of peritoneal metastasis that can improve the therapeutic ratio between toxicity and therapeutic efficacy.

Antitumor activity of intraperitoneal paclitaxel in orthotopic patient-derived xenograft models of mucinous appendiceal adenocarcinoma

“…Although less weight loss was observed with IP relative to IV dosing, significant weight loss was seen with higher doses of IP paclitaxel suggesting that further drug modification to further increase the peritoneal concentration would improve therapeutic window. Recently a nanoparticle delivery method using cabazitaxel encapsulated in alginate microspheres has shown promise in this regard (22). Although paclitaxel is active in many gastrointestinal malignancies including gastric, esophageal, and small bowel adenocarcinoma, neither IP nor IV paclitaxel have been prospectively tested in AA, which is likely a legacy of the historic treatment of AA with chemotherapy developed for CRC.…”

“…Recently a nanoparticle delivery method using cabazitaxel encapsulated in alginate microspheres has shown promise in this regard (22). Although paclitaxel is active in many gastrointestinal malignancies including gastric, esophageal, and small bowel adenocarcinoma, neither IP nor IV paclitaxel have been prospectively tested in AA, which is likely a legacy of the historic treatment of AA with chemotherapy developed for CRC.…”

Seaweed: a sustainable solution for greening drug manufacturing in the pursuit of sustainable healthcare

“…Alginate-based hydrogels, for example, can be used to encapsulate drugs and provide sustained release profiles. The gels can be tailored to control the release rate of drugs, allowing for a more precise dosing regimen, using basic systems, such as cross-linking techniques [155]. Additionally, seaweed-based nanoparticles and microspheres have been investigated as drug carriers [156].…”

Peritoneal Metastasis: A Dilemma and Challenge in the Treatment of Metastatic Colorectal Cancer

“…Poly(cyano-cyanoacrylate) (PACA) NPs loaded with cabazitaxel (CAB) were also shown to improve the therapeutic response in the PM model [290]. Fleten et al also developed a new delivery system by encapsulating NPs containing CAB-PACA in alginate microspheres and experimentally illuminated that PACAlg not only provides higher peritoneal drug concentrations and tuned drug release rates but also reduces cytotoxicity [291]. Those may become promising therapeutic strategies for CRC-PM patients.…”