Pharmacokinetic Consequences of PLGA Nanoparticles in Docetaxel Drug Delivery

Abstract

Background: Cancer chemotherapy is accompanied with administration of highly potent cytotoxic agents in doses that can result in non-specific drug toxicity and side effects. Chemotherapeutic agents possess limitations such as lack of water solubility, high volume of distribution, poor bioavailability, narrow therapeutic indices, multi-drug resistance, etc. that raise serious matters of concern regarding drug's pharmaceutical and clinical aspects. However, application of nanoparticles in delivery of anti-cancer agents has been a popular approach to address these concerns. Poly (lactide-co-glycolide) (PLGA), a biocompatible/biodegradable FDA-approved polymer has been widely used as drug carrier to enhance pharmaceutical/therapeutic properties of anticancer agents, prolonging their circulation time, targeting cancer tissues or protecting the drug from rapid elimination/premature degradation. This favourably modifies drug's pharmacokinetics and pharmacodynamics.

Objective: This paper provides a general perspective on how association of docetaxel to PLGA nanoparticles potentially modifies pharmacokinetics and biodistribution profile of the anticancer agent.

Method: A comprehensive literature search has been conducted and dedicated to compile most relevant and up-to-date material about pharmacokinetic consequences of PLGA nanoparticles in docetaxel drug delivery.

Results: A set of determinants are considered to be influential on biodistribution and fate of docetaxel and PLGA nanoparticles. These are attributed to physicochemical properties of PLGA polymer, docetaxel, nanoparticle, and the set of events imposed to the nanoparticles by the host body.

Conclusion: Association of PLGA nanoparticles and docetaxel has demonstrated to modify the drug's pharmacokinetic and biodistribution profile.

Keywords: Pharmacokinetics; biodistribution; docetaxel.; poly (lactide-co-glycolide) (PLGA); poly (lactide-co-glycolide)-poly (ethylene glycol) (PLGA-PEG); polymeric nanoparticles.