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.

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“…These nanosize carriers contain a hydrophilic shell and a hydrophobic core that may serve as a reservoir for hydrophobic drugs. [12] …”

“…[12] This small size offers many advantages, such as evading scavenging by the phagocytic system in the liver and bypassing filtration of the interendothelial cells in the spleen. These two advantages result in longer circulation time and accumulation of the micelles at tissue site with the vascular abnormality (might be useful in delivering anticancer drugs).…”

“…These two advantages result in longer circulation time and accumulation of the micelles at tissue site with the vascular abnormality (might be useful in delivering anticancer drugs). [12] There are some different methods which are used to study micelle dimensions including dynamic light scattering, static light scattering, atomic force microscopy (AFM), and transmission electron microscopy (TEM). AFM and TEM give direct images and insight into shape.…”

“…[19] Since PEG is easily oxidized, the lower molecular weight of PEG is preferable and generally use as a solvent and higher molecular weight is used as a component in the micelle, possibly due to the fact that oxidative degradation significantly decreases with increasing molar mass. [12] There are some other polymers which are used as hydrophilic shell-forming polymer including: a. Poly (N-vinyl-2-pyrrolidone) [20] The surfactant molecules are separated (left). Above CMC: Surfactant molecules are assembled and formed a micelle (right) [8] b. Poly(N-(2-hydroxypropyl) methacrylamide): It is a nonimmunologic polymer which is multifunctional and several ligands can be attached to, to use in targeting drug delivery.…”

“…[25] Core capacity is affected by three different factors: Compatibility, [13] hydrophilic-lipophilic balance (HLB), [26] and the polymer-drug ratio (P/D ratio). [12] 1. Compatibility: Since each drug has its own unique chemical and physical properties, no delivery vehicle prepared from a particular polymer will assist as a universal carrier for all drugs.…”