Predicting the Loading Capability of mPEG-PDLLA to Hydrophobic Drugs Using Solubility Parameters†

Summary of main observation and conclusion Physical encapsulation of drugs into polymer micelles is a common method of loading hydrophobic drugs. Methoxy polyethylene glycol-poly( D , L -lactide) (mPEG-PDLLA) is one of the most commonly used drug carrier. At present, whether a carrier is suitable for the loading of a certain drug is determined by drug loading experiments. This process costs a lot of time. Therefore, an efficient predicting method to avoid time-consuming tests is critical. In this study, we prepared mPEG 5k -PDLLA 5k and used it to load a series of drugs. Three parameters were used to test the miscibility of mPEG 5k -PDLLA 5k with drugs, including absolute difference in Hildebrand solubility parameters (|Δ δ |), Flory–Huggins interaction parameter ( χ ) and the distance ( D value) calculated from the two-dimensional solubility parameters. We found the two-dimensional solubility parameters obtained from JB2013 group contribution (GC) method was useful. By comparing the drug loading content (DLC) with the D value, we found that when the D value was less than 5.0 (MJ/m 3 ) 1/2 , the miscibility of drug and mPEG 5k -PDLLA 5k was good and drug loading capability was high; when the D value was more than 8.0 (MJ/m 3 ) 1/2 , the drug was barely loaded. Thus, this work provided a rationale to qualitatively predict the loading capability of mPEG 5k -PDLLA 5k for hydrophobic drugs.