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

Abstract

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 mPEG5k‐PDLLA5k and used it to load a series of drugs. Three parameters were used to test the miscibility of mPEG5k‐PDLLA5k with drugs, including absolute difference in Hildebrand solubility parameters (|Δδ|), 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/m3)1/2, the miscibility of drug and mPEG5k‐PDLLA5k was good and drug loading capability was high; when the D value was more than 8.0 (MJ/m3)1/2, the drug was barely loaded. Thus, this work provided a rationale to qualitatively predict the loading capability of mPEG5k‐PDLLA5k for hydrophobic drugs.

Evolution of the Computational Pharmaceutics Approaches in the Modeling and Prediction of Drug Payload in Lipid and Polymeric Nanocarriers

“…PLGA nanoparticles (R 2 of 0.61). In contrast, ∆δ values obtained by Sun et al [18] did not distinguish between high and low DL in the PLA core of the prepared PEG-PLA micells. Similarly, their X H values did not provide a well-defined miscibility region and therefore could not predict well the DL capability of these micelles (Table 1).…”

“…It is a thermodynamic model first introduced in the world of polymers to explain their behavior in solutions [ 12 ], and this is well documented in polymers literature [ 13 , 14 , 15 ]. Recently, this technique was used to extract valuable information regarding the plausible loading of many drugs in polymeric [ 16 , 17 , 18 , 19 ] and even lipid [ 20 ]—carriers via predicting their mutual solubility/miscibility. It is well known that one of the most important factors that determine the loading capacity of a carrier is the solubility of the drug in this carrier [ 10 , 21 , 22 ].…”

A Novel Vascular Disrupting Agents Noncovalent Polymeric Nanomedicine: Significantly Increased Antitumor Therapeutic Efficiency

“…HBP NPs were prepared via the nanoprecipitation method. [ 47‐48 ] The drug loading content (DLC%) and loading efficiency (DLE%) in HBP NPs were calculated by the standard curve and the peak area, which were labeled in Figure 2A. Through calculation, the DLC% and DLE% were 16.5 wt% and 82.7%, respectively.…”

Polymeric capsules and micelles as promising carriers of anticancer drugs

“…48 The capability of (m)PEG-PDLLA micelles to be efficiently loaded with hydrophobic drugs can be qualitatively predicted based on calculated solubility parameters. 49 The PEG-PDLLA nanocarriers have already been tested with paclitaxel, 50 doxorubicin 51 and tanespimycin. 39 One of the most studied drugs -doxorubicin -was also encapsulated in vehicles prepared using biocompatible copolymer composed of PEO and poly(γ-benzyl l-glutamate) (PBLG), which is synthetic polypeptide with the ability to form secondary structures such as α-helices or β-strands.…”