Formulation of Drugs in Block Copolymer Micelles: Drug Loading and Release

Abstract

Block copolymer micelles have become accepted as a viable strategy for drug formulation and delivery. Block copolymer micelles may serve as solubilizers and/or true drug carriers depending on their drug retention properties in vivo. Indeed the formulation of hydrophobic drugs in these micelle systems has been shown to provide up to a 30,000 fold increase in the water solubility of some compounds. In addition, the administration of drugs in copolymer micelles has been shown to reduce their toxicity and improve their therapeutic efficacy. The present review is focused on the drug loading and release properties of block copolymer micelles. Specifically, the properties of the drug, properties of the micelle core and the presence of interactions between the drug and the core-forming block are discussed in terms of their influence on the drug loading and release properties of the micelles. The various methods employed to prepare drug-loaded micelles are reviewed and the in vitro release assays used to predict the in vivo release characteristics of the formulations are discussed. The balance between drug loading and micelle stability is highlighted as a critical factor in the optimization of micelle-based formulations. The in vivo performance of micelles as delivery systems is evaluated by comparing the pharmacokinetics of free drug and drug administered in micelle-based formulations. Overall, the composition-property and property-performance relationships outlined in this review may aid in guiding the rational design of block copolymer micelles for drug delivery. In addition, suggestions for future research in this area are provided as a means to assist in furthering block copolymer micelles as one of the leading advanced drug delivery technologies for the systemic administration of drugs.

Self-assembled mPEG–PCL-g–PEI micelles for simultaneous codelivery of chemotherapeutic drugs and DNA: synthesis and characterization in vitro

“…Drug-delivery systems based on block copolymer micelles are considered to be a promising approach for improving the therapeutic index and reducing systemic toxicity. [28][29][30] As an amphiphilic diblock copolymer, the biodegradable PCL-PEG copolymer is widely studied for its self-assembling properties and its potential use as a drug carrier. 31,32 PEG chains on nanoparticle surfaces have been described as efficient drug carriers in the bloodstream with a range of applications, including prolonging the systemic cycle time of colloidal drug delivery systems and evading recognition by cells of the mononuclear phagocyte system.…”

Polymeric Micelles: Nanocarriers for Cancer-Targeted Drug Delivery

“…The last decade has seen significant progress in the development of various micellar systems for targeted delivery of anticancer agents (5,29,30). However, much improvement is still needed for the existing systems with respect to drug-loading capacity and formulation stability.…”

Macromolecular composition and drug-loading effect on the delivery of paclitaxel and folic acid from acrylic matrices

“…In addition, side-effects due to the toxicity towards healthy tissues limit the administration doses, compromising the effectiveness of the treatment (Van Zuylen et al, 2001). The common practice to incorporate hydrophobic and poor water-soluble drugs within biocompatible materials has been shown to significantly reduce systemic toxicity and in the meanwhile to increase the drug solubility (Torchilin, 2004;Liu et al, 2006;Nishiyama & Kataoka, 2006;Silvestri et al, 2009a). Novel drug delivery systems are currently studied and developed to optimize drug release profiles with the aim to be employed in different therapeutic areas.…”