Figueroa, Sara and Fleischmann, Daniel and Beck, Sebastian and Goepferich, Achim (2020) Thermodynamic, Spatial and Methodological Considerations for the Manufacturing of Therapeutic Polymer Nanoparticles. PHARMACEUTICAL RESEARCH, 37 (3): 59. ISSN 0724-8741, 1573-904X
Full text not available from this repository. (Request a copy)Abstract
Purpose Evaluate fundamental parameters that dictate the effectiveness of drug loading. Methods A model water-soluble drug lacking ionizable groups, pirfenidone (PFD), was encapsulated through nanoprecipitation in poly(ethylene glycol)-poly(lactic acid) (PEG-PLA)-poly(lactic-co-glycolic acid) (PLGA) NPs. Firstly, the thermodynamic parameters predicting drug-polymer miscibility were determined to assess the system's suitability. Then, the encapsulation was evaluated experimentally by two different techniques, bulk and microfluidic (MF) nanoprecipitation. Additionally, the number of molecules that fit in a particle core were calculated and the loading determined experimentally for different core sizes. Lastly, the effect of co-encapsulation of alpha-lipoic acid (LA), a drug with complementary therapeutic effects and enhanced lipophilicity, was evaluated. Results The thermodynamic miscibility parameters predicted a good suitability of the selected system. MF manufacturing enhanced the encapsulation efficiency by 60-90% and achieved a 2-fold higher NP cellular uptake. Considering spatial constrictions for drug encapsulation and increasing the size of the PLGA core the number of PFD molecules per NP was raised from under 500 to up to 2000. More so, the co-encapsulation of LA increased the number of drug molecules per particle by 96%, with no interference with the release profile. Conclusions Thermodynamic, spatial and methodological parameters should be considered to optimize drug encapsulation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SOLUBILITY PARAMETERS; PLGA NANOPARTICLES; POLYETHYLENE-GLYCOL; RATIONAL DESIGN; PIRFENIDONE; DRUG; PEG; NANOPRECIPITATION; MICELLES; encapsulation; microfluidics; nanoprecipitation; pirfenidone; polymeric nanoparticles |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Mar 2021 07:08 |
| Last Modified: | 30 Mar 2021 07:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45077 |
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