Miller, Tobias and Breyer, Sandra and van Colen, Gwenaelle and Mier, Walter and Haberkorn, Uwe and Geissler, Simon and Voss, Senta and Weigandt, Markus and Goepferich, Achim (2013) Premature drug release of polymeric micelles and its effects on tumor targeting. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 445 (1-2). pp. 117-124. ISSN 0378-5173, 1873-3476
Full text not available from this repository. (Request a copy)Abstract
Based on the enhanced permeability and retention (EPR) effect, nanoparticles are believed to accumulate in tumors. In this conjunction, the stability of drug encapsulation is assumed to be sufficient. For clarification purposes, PEGylated poly-(D,L-lactic acid) (PEG-PDLLA) micelles which incorporated the hydrophobic model drug dechloro-4-iodo-fenofibrate (IFF) were investigated. H2N-PEG-PDLLA was synthesized, coupled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and labeled with 111-indium. From this polymeric species, mixed micelles with H3CO-PEG-PDLLA were prepared which encapsulated the 125-iodine or 131-iodine labeled drug IFF. Bioimaging and biodistribution experiments in healthy and AR42J-tumor bearing mice were carried out to quantify the uptake of the drug and its carrier in single organs. As a result, upon injection of this system, a rapid dissociation of the polymeric carrier and the incorporated drug (<10 min post inj.) was revealed. Regardless of the premature release, the drug showed an enhanced tumor accumulation compared to the polymeric carrier. In conclusion, the self-assembling system allowed for successful solubilization of the hydrophobic drug by physical incorporation into micelles whereas the tumor targeting properties of the drug delivery system could not be sufficiently shown. (C) 2013 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PLASMA PARTITION-COEFFICIENTS; BLOCK-COPOLYMER MICELLES; LIPOSOMAL DOXORUBICIN; PACLITAXEL FORMULATION; DELIVERY; STABILITY; NANOPARTICLES; FENOFIBRATE; BIODISTRIBUTION; PERMEABILITY; Polymeric micelles; Organ distribution; Bioimaging; Tumor accumulation; EPR effect; Premature release |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Apr 2020 06:11 |
| Last Modified: | 23 Apr 2020 06:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16991 |
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