Drug Loading of Polymeric Micelles

Abstract

Careful solvent selection prior to cosolvent evaporation was a beneficial approach to load hydrophobic drugs into polymeric micelles. Moreover, β-cyclodextrins could be used as versatile lyoprotectors for these micelles.

Supersaturated polymeric micelles for oral cyclosporine A delivery

“…Super-PMs can be prepared using the hot melt extrusion-hydration method. When drugs are administered as a Super-PM solution, drug thermodynamic activity is greatly increased, compared with commonly used micelles prepared by direct dissolution of the drug in an empty micelle solution or direct dialysis method [20]. Micelles prepared by direct dissolution or dialysis methods have a low amount of drug incorporated and show limited release of free drug from the micelle particles [7,21,22].…”

Polymeric micelles for oral drug administration enabling locoregional and systemic treatments

“…2.1 Methods to prepare drug-loaded polymeric micelles Methods to prepare micelles mainly depend on the aqueous solubility of both the copolymer and the drug ( Table 1) [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. Direct dissolution in water or buffer is the simplest approach when water-soluble copolymers are used (e.g., Pluronics) [33,38].…”

“…Generally, the drug is added in excess to the micellar solution, and the system is then subjected to mild temperature or mechanically mixed to promote the migration of the dissolved drug molecules toward the micelle core [60]. If the block copolymers are not readily soluble in water, the drug and the copolymers are dissolved in an organic solvent, which is afterward replaced with water by means of dialysis [47]. The choice of the organic solvent needs to be careful, because the solvent influences the size distribution of polymeric micelles [9].…”

“…The block copolymer has to be stable in the organic solvent Difficulty to clean away free drugs and organic solvents Amphotericin B [46] Dexamethasone [47] Griseofulvin [48] Paclitaxel [49] Evaporation or film method Poorly water-soluble copolymers. High drug-loading and encapsulation efficiency Only suitable for low-HLB polymers Diazepam [50] Docetaxel [51] Genistein [52] Indomethacin [53] Freeze-drying and microphase separation Drug and copolymer is dissolved in water/organic cosolvent mixture Risk of residual organic solvents Docetaxel [54] Gliclazide [55] Naproxen [56] Oil-in-water emulsion Easy preparation of polymeric micelles with controlled and uniform size Difficulty to clean away free drugs and organic solvents Bovine serum albumin [57] Heparin [58] Fenofibrate [59] HLB: Hydrophilic--lipophilic balance.…”

Materials innovation for co-delivery of diverse therapeutic cargos

“…Similarly to linear polymers, these are of a size that allows them to take advantage of the enhanced permeation and retention effect in cancer treatment, and the hydrophilic corona often offers protection from phagocytic activity, resulting in prolonged stability in circulation 88 . The formation of the block copolymers themselves as well as the methods of loading polymeric micelles with drugs have been reviewed elsewhere 88, 90 , so we will focus instead on progress that has been made in the area of specifically modifying carriers to make them ideal for co-delivery of two or more therapeutics.…”