Size and Size Distribution

Block copolymer micelles typically range in size from 10 to 100 nm. As a result of their small size and the steric stabilization provided by the hydrophilic corona, micelles are less susceptible to MPS clearance.14,15 In addition, their small size allows them to extravasate through the leaky endo-thelium and accumulate at the tumor interstitium. Therefore, micelles can passively target tumors via the enhanced permeability and retention (EPR) effect.1,16 Micelles can also pass through the pores of the renal filtration system as individual polymer chains following disassembly. A renal threshold limit of less than 50,000 g/mol has been reported for polymeric carriers,17 so it is important to design a micelle system where the individual polymer chains have a molecular weight that is lower than this threshold limit. The small size of the micelles also allows for sterilization by filtration in order to remove bacteria prior to intravenous administration.

Filtration can also be used to reduce the size distribution of colloidal carriers that have broad distributions following initial preparation. Micelles tend to have a relatively narrow size distribution; however, they are prone to secondary aggregation because of insufficient coverage of the hydrophobic core by the hydrophilic chains. Dilution has been shown to be useful in breaking apart the secondary aggregates of primary micelles.18

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