Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs

Abstract

Poorly soluble drugs often encounter low bioavailability and erratic absorption patterns in the clinical setting. Due to the rising number of compounds having solubility issues, finding ways to enhance the solubility of drugs is one of the major challenges in the pharmaceutical industry today. Polymeric micelles, which form upon self-assembly of amphiphilic macromolecules, can act as solubilizing agents for delivery of poorly soluble drugs. This manuscript examines the fundamentals of polymeric micelles through reviews of representative literature and demonstrates possible applications through recent examples of clinical trial developments. In particular, the potential of polymeric micelles for delivery of poorly water-soluble drugs, especially in the areas of oral delivery and in cancer therapy, is discussed. Key considerations in utilizing polymeric micelles' advantages and overcoming potential disadvantages have been highlighted. Lastly, other possible strategies related to particle size reduction for enhancing solubilization of poorly water-soluble drugs are introduced.

Keywords: Anticancer; Clinical trial; Drug solubilization; Micelle stability; Nanocrystal; Nanoemulsion; Oral delivery; Polymeric micelle.

Figure 1

Schematic representation of supramolecular structure of polymeric micelles.

Figure 2

Schematic summary of the pathways by which polymeric micelles may interact with the intestinal mucosa. A) receptor-mediated endocytosis; B) pinocytosis; C) Efflux of drug molecules

Figure 3

(A) Pharmacokinetic profile of DTXL-TNP in humans: A) comparison of plasma concentration time profile of DTXL-TNP at a dose of 30 mg/m² compared to published sb-DTXL data at the same dose in patients with advanced solid tumors (n=3). (B) Plasma concentration time profile in dose-ranging studies over the first 8 hours after single dose administration of DTXL-TNP. (Figures adapted from Reference 96).