| Autor: |
Tang S; Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, California 94080, United States., Pederson Z; Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, California 94080, United States., Meany EL; Department of Bioengineering, Stanford University, Stanford, California 94305, United States., Yen CW; Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, California 94080, United States., Swansiger AK; Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon 97403, United States., Prell JS; Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon 97403, United States., Chen B; Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, California 94080, United States., Grosskopf AK; Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech, Inc, South San Francisco, California 94080, United States., Eckman N; Department of Chemical Engineering, Stanford University, Stanford, California 94305, United States., Jiang G; Department of Bioengineering, Stanford University, Stanford, California 94305, United States., Baillet J; Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States., Pellett JD; Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, California 94080, United States., Appel EA; Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States. |
| Abstrakt: |
Supramolecular hydrogels formed through polymer-nanoparticle interactions are promising biocompatible materials for translational medicines. This class of hydrogels exhibits shear-thinning behavior and rapid recovery of mechanical properties, providing desirable attributes for formulating sprayable and injectable therapeutics. Characterization of hydrogel composition and loading of encapsulated drugs is critical to achieving the desired rheological behavior as well as tunable in vitro and in vivo payload release kinetics. However, quantitation of hydrogel composition is challenging due to material complexity, heterogeneity, high molecular weight, and the lack of chromophores. Here, we present a label-free approach to simultaneously determine hydrogel polymeric components and encapsulated payloads by coupling a reversed phase liquid chromatographic method with a charged aerosol detector (RPLC-CAD). The hydrogel studied consists of modified hydroxypropylmethylcellulose, self-assembled PEG- b -PLA nanoparticles, and a therapeutic compound, bimatoprost. The three components were resolved and quantitated using the RPLC-CAD method with a C4 stationary phase. The method demonstrated robust performance, applicability to alternative cargos ( i.e. , proteins) and was suitable for composition analysis as well as for evaluating in vitro release of cargos from the hydrogel. Moreover, this method can be used to monitor polymer degradation and material stability, which can be further elucidated by coupling the RPLC method with (1) a multi-angle light scattering detector (RPLC-MALS) or (2) high resolution mass spectrometry (RPLC-MS) and a Fourier-transform based deconvolution algorithm. We envision that this analytical strategy could be generalized to characterize critical quality attributes of other classes of supramolecular hydrogels, establish structure-property relationships, and provide rational design guidance in hydrogel drug product development. |
