PMID- 35025461 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220113 IS - 2576-6422 (Electronic) IS - 2576-6422 (Linking) VI - 3 IP - 7 DP - 2020 Jul 20 TI - Elucidating the Molecular Interactions of Encapsulated Doxorubicin within a Nonionic, Thermoresponsive Polyester Coacervate. PG - 4626-4634 LID - 10.1021/acsabm.0c00507 [doi] AB - Thermoresponsive polymers that display a lower critical solution temperature (LCST) are attractive drug delivery systems (DDSs) due to their potential to encapsulate and release therapeutics in a sustained manner as a function of temperature input. To attain the full potential of such DDSs, methods that illustrate the details of drug-polymer interactions are necessary. Here, we synthesized a nonionic, coacervate-forming, thermoresponsive polyester to encapsulate doxorubicin (Dox) and used solution state NMR spectroscopy and fluorescence microscopy techniques to probe the interactions between the polymer and Dox at the molecular level. The incomplete dehydration provides a matrix for encapsulation of sensitive therapeutics and preserving their activity, while the low hysteresis property of the polyester provides rapid transition from soluble to coacervate phase. Saturation transfer difference (STD) NMR revealed the Dox-polymer interactions within the coacervates. (1)H-(1)H nuclear Overhauser effect spectroscopy (NOESY) cross-peak differences of Dox confirmed the Dox-polymer interactions. Diffusion-ordered spectroscopy (DOSY) revealed the slower diffusion rate of Dox in the presence of polyester coacervates. These studies illustrate how the state of the polyester (below and above LCST) affects the polyester-Dox interactions and offers details of the specific functional groups involved in these interactions. Our results provide a framework for future investigations aimed at characterizing fundamental interactions in polymer-based DDSs. FAU - Kundu, Mangaldeep AU - Kundu M AUID- ORCID: 0000-0003-2555-0474 AD - Department of Polymer Science, The University of Akron, Akron, Ohio 44325, United States. FAU - Morris, Daniel L AU - Morris DL AD - Department of Chemistry and Biochemistry, The University of Akron, Akron, Ohio 44325, United States. FAU - Cruz, Megan A AU - Cruz MA AD - Department of Polymer Science, The University of Akron, Akron, Ohio 44325, United States. FAU - Miyoshi, Toshikazu AU - Miyoshi T AUID- ORCID: 0000-0001-8344-9687 AD - Department of Polymer Science, The University of Akron, Akron, Ohio 44325, United States. FAU - Leeper, Thomas C AU - Leeper TC AD - College of Science and Mathematics, Kennesaw State University, Kennesaw, Georgia 30144, United States. FAU - Joy, Abraham AU - Joy A AUID- ORCID: 0000-0001-7781-3817 AD - Department of Polymer Science, The University of Akron, Akron, Ohio 44325, United States. LA - eng PT - Journal Article DEP - 20200708 PL - United States TA - ACS Appl Bio Mater JT - ACS applied bio materials JID - 101729147 SB - IM OTO - NOTNLM OT - controlled release polyester OT - drug delivery system OT - nonionic coacervate OT - polyester coacervate OT - smart polymers OT - stimuli responsive materials OT - thermoresponsive polymers EDAT- 2020/07/20 00:00 MHDA- 2020/07/20 00:01 CRDT- 2022/01/13 17:14 PHST- 2022/01/13 17:14 [entrez] PHST- 2020/07/20 00:00 [pubmed] PHST- 2020/07/20 00:01 [medline] AID - 10.1021/acsabm.0c00507 [doi] PST - ppublish SO - ACS Appl Bio Mater. 2020 Jul 20;3(7):4626-4634. doi: 10.1021/acsabm.0c00507. Epub 2020 Jul 8.