A biocompatible superparamagnetic chitosan-based nanoplatform enabling targeted SN-38 delivery for colorectal cancer therapy

30-99% of administered nanoparticles will accumulate and sequester in the liver after administration into the body. This results in reduced delivery to the targeted diseased tissue and potentially leads to increased toxicity at the hepatic cellular level. This review article focuses on the inter- and intra-cellular interaction between nanoparticles and hepatic cells, the elimination mechanism of nanoparticles through the hepatobiliary system, and current strategies to manipulate liver sequestration. The ability to solve the "nanoparticle-liver" interaction is critical to the clinical translation of nanotechnology for diagnosing and treating cancer, diabetes, cardiovascular disorders, and other diseases.

Irinotecan hydrochloride is a camptothecin derivative that exerts antitumor activity against a variety of tumors. SN-38 produced in the body by carboxylesterase is the active metabolite of irinotecan. After irinotecan was introduced for the treatment of metastatic colorectal cancer (CRC) at the end of the last century, survival has improved dramatically. Irinotecan is now combined with 5-fluorouracil, oxaliplatin and several molecularly-targeted anticancer drugs, resulting in the extension of overall survival to longer than 30 mo. Severe, occasionally life-threatening toxicity occurs sporadically, even in patients in relatively good condition who have a low risk of chemotherapy-induced toxicity, often causing the failure of irinotecan-based chemotherapy. Clinical pharmacological studies have revealed that such severe toxicity is related to exposure to SN-38 and genetic polymorphisms in UDP-glucuronosyltransferase 1A1 gene. The large inter- and intra-patient variability in systemic exposure to SN-38 is determined not only by genetic factors but also by physiological and environmental factors. This review first summarizes the roles of irinotecan in chemotherapy for metastatic CRC and then discusses the optimal dosing of irinotecan based on the aforementioned factors affecting systemic exposure to SN-38, with the ultimate goal of achieving personalized irinotecan-based chemotherapy.

Polyelectrolyte complexes (PECs) as safe drug delivery carriers, are spontaneously formed by mixing the oppositely charged polyelectrolyte solutions in water without using organic solvents nor chemical cross-linker or surfactant. Intensifying attentions on the PECs study are aroused in academia and industry since the fabrication process of PECs is mild and they are ideal vectors for the delivery of susceptible drugs and macromolecules. Chitosan as the unique natural cationic polysaccharide, is a good bioadhesive material. Besides, due to its excellent biocompatibility, biodegradability, abundant availability and hydrophilic nature, chitosan-based PECs have been extensively applied for drug delivery, particularly after administration through mucosal and parenteral routes. The purpose of this review is to compile the recent advances on the biomedical applications of chitosan-based PECs, with specific focuses on the mucosal delivery, cancer therapy, gene delivery and anti-HIV therapy. The challenges and the perspectives of the chitosan-based PECs are briefly commented as well.