title: Current Update of a Carboxymethylcellulose-PEG Conjugate Platform for Delivery of Insoluble Cytotoxic Agents to Tumors.
abstract: Cytotoxic chemotherapeutic agents are used as the standard therapy for a range of significant cancers, but many of these drugs suffer from poor water solubility and low selectivity, limiting their clinical efficacy. To overcome these shortcomings, Cellax™ drug delivery platform was developed. Cellax™ is a polymer-based nanoparticle drug delivery system designed to solubilize hydrophobic drugs and target them to solid tumors, thereby enhancing the efficacy and reducing the side effects. Cellax-docetaxel (Cellax-DTX) displayed improved pharmacokinetic, safety, and efficacy profiles compared to native DTX (Taxotere®) and Nab-paclitaxel (Nab-PTX, Abraxane®) in multiple animal models. Cellax-DTX was shown to interact with serum albumin and SPARC (secreted protein acidic and rich in cysteine) that is highly expressed by tumor stromal cells, leading to superior stroma depleting activity in orthotopic breast and pancreatic tumor models and subsequently reduced incidence of visceral metastases compared to free DTX and Nab-PTX. The Cellax™ platform was employed to deliver podophyllotoxin (Cellax-PPT) and cabazitaxel (Cellax-CBZ), and increased their safety and efficacy against multidrug-resistant tumors. This review discusses the rational design of the Cellax™ platform and summarizes the preclinical results. A multifunctional version of Cellax™ and a biomarker for predicting Cellax™ efficacy were developed and identified to promote the personalized use. Perspectives and future plans for this platform technology are also provided.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver Campus, 5519-2405 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Drug Delivery and Formulation, Drug Discovery Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, Ontario, M5G 0A3, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Bteich
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver Campus, 5519-2405 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada. shyh-dar.li@ubc.ca.
authors.forename: Shyh-Dar
authors.initials: SD
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D011092:Polyethylene Glycols; D002266:Carboxymethylcellulose Sodium
keywords: Cellax; antitumor efficacy; nanoparticle; pharmacokinetics; tumor microenvironment