Polyester-based micelles and nanoparticles for the parenteral delivery of taxanes.
Taxanes are potent antimitotic agents that have demonstrated efficacy in a wide range of malignancies. Due to their poor water-solubility, these cytostatic drugs were first formulated with low molecular weight surfactants, e.g. Cremophor EL (CrEL) and Tween 80 (polysorbate 80), which are known to exhibit serious adverse effects in humans. In recent years, there has been growing interest in the design of more biocompatible formulations for both paclitaxel and docetaxel. Polymer-based drug carriers represent an attractive venue given the diversity in the array of existing polymers. Most notably, biopolyesters are vastly employed in the field of biomedical research given their biocompatibility and biodegradability. Polyester-based micelles and nanoparticles have been applied to the parenteral delivery of taxanes with varying degrees of success. Block copolymer micelles possess a unique core-shell structure generated through the self-assembly of amphiphilic copolymers in aqueous media. Although these systems have shown greatly enhanced tolerability compared to formulations based on low molecular weight surfactants, in some cases their failure to retain their cargo following parenteral administration has hindered their capacity to target taxanes to solid tumours. While polyester-based nanoparticles possess comparatively greater stability and drug targeting capacity, they frequently display a significant burst effect whereby a major portion of the cargo is immediately discarded from the carrier upon injection. This review focuses on the current application of polyester-based micelles and nanoparticles to the tumour targeting of taxanes. The preparation, loading efficiencies, release kinetics, cytotoxicity and in vivo behaviour of these systems is discussed in detail.
Gaucher
Geneviève
G
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Downtown Station, Montreal, QC, Canada H3C 3J7.
Marchessault
Robert H
RH
Leroux
Jean-Christophe
JC
D000818:Animals; D050256:Antimitotic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D007263:Infusions, Parenteral; D008823:Micelles; D008958:Models, Molecular; D015394:Molecular Structure; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry* / Q000633:toxicity; D012995:Solubility; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution
D050256:Antimitotic Agents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D043823:Taxoids