PMID- 31051231 OWN - NLM STAT- MEDLINE DCOM- 20191202 LR - 20191202 IS - 1873-3476 (Electronic) IS - 0378-5173 (Linking) VI - 565 DP - 2019 Jun 30 TI - In vitro evaluation of innovative light-responsive nanoparticles for controlled drug release in intestinal PDT. PG - 199-208 LID - S0378-5173(19)30348-5 [pii] LID - 10.1016/j.ijpharm.2019.04.077 [doi] AB - Nanoparticles (NP) have gained importance as drug delivery systems for pharmaceutical challenging drugs. Their size properties allow passive targeting of cancer tissue by exploiting the enhanced permeability and retention (EPR) effect. Furthermore, surface modifications enable an active drug targeting for diseased regions in the human body. Besides the advantages, the drug release from commonly used biodegradable NP is mostly depending on physiological circumstances. Hence, there is a need for a more controllable drug release. The use of light-responsive polymers is an innovative conception enabling a more distinct drug release by an external light stimulus. The idea provides potential for an increase in efficiency and safety of local therapies. In this study, innovative light-sensitive NP were investigated for a photodynamic therapy (PDT) of gastrointestinal tumors. Nanoparticles based on a newly developed light-responsive polycarbonate (LrPC) and poly(lactic-co-glycolic-acid) (PLGA) were loaded with the approved photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (mTHPC). Mucus penetrating properties were obtained by surface PEGylation of the nanoparticles either by using LrPC in combination with a PEGylated PLA (PEG-PLA) or by a combination with PEGylated LrPC (LrPC-PEG). Cytotoxic potential in dependency of a light-induced drug release was investigated in different cytotoxicity assays. Intracellular accumulation in mucus producing colon-carcinoma cell line HT-29-MTX was analysed by HPLC and confocal laser microscopy. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Mahlert, Laura AU - Mahlert L AD - Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstrasse 48, 48149 Muenster, Germany. Electronic address: l.mahlert@uni-muenster.de. FAU - Anderski, Juliane AU - Anderski J AD - Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstrasse 48, 48149 Muenster, Germany. Electronic address: j.anderski@uni-muenster.de. FAU - Schoppa, Timo AU - Schoppa T AD - Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstrasse 48, 48149 Muenster, Germany. Electronic address: schoppat@uni-muenster.de. FAU - Mulac, Dennis AU - Mulac D AD - Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstrasse 48, 48149 Muenster, Germany. Electronic address: mulac.dennis@uni-muenster.de. FAU - Sun, Jingjiang AU - Sun J AD - Department of Chemistry, Paderborn University, Warburger Str. 100, 33098 Paderborn, Germany; Qingdao University of Science and Technology, School of Polymer Science and Engineering, Zhengzhou Rd. 53, CN-266042 Qingdao, China. Electronic address: sunjij@qust.edu.cn. FAU - Kuckling, Dirk AU - Kuckling D AD - Department of Chemistry, Paderborn University, Warburger Str. 100, 33098 Paderborn, Germany. Electronic address: dirk.kuckling@uni-paderborn.de. FAU - Langer, Klaus AU - Langer K AD - Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstrasse 48, 48149 Muenster, Germany. Electronic address: k.langer@uni-muenster.de. LA - eng PT - Journal Article DEP - 20190430 PL - Netherlands TA - Int J Pharm JT - International journal of pharmaceutics JID - 7804127 RN - 0 (Delayed-Action Preparations) RN - 0 (Mesoporphyrins) RN - 0 (Photosensitizing Agents) RN - 0 (Polymers) RN - FU21S769PF (temoporfin) SB - IM MH - Cell Survival/drug effects MH - DNA Damage MH - Delayed-Action Preparations/administration & dosage/chemistry/radiation effects MH - HT29 Cells MH - Humans MH - Intestinal Neoplasms/*drug therapy MH - Light MH - *Mesoporphyrins/administration & dosage/chemistry/radiation effects MH - *Nanoparticles/administration & dosage/chemistry/radiation effects MH - *Photochemotherapy MH - *Photosensitizing Agents/administration & dosage/chemistry/radiation effects MH - Polymers/administration & dosage/chemistry/radiation effects OTO - NOTNLM OT - Controlled drug delivery OT - HT-29-MTX cells OT - Intestinal cancer OT - Light-responsive polymers OT - Photodynamic therapy EDAT- 2019/05/06 06:00 MHDA- 2019/12/04 06:00 CRDT- 2019/05/04 06:00 PHST- 2018/12/18 00:00 [received] PHST- 2019/04/28 00:00 [revised] PHST- 2019/04/29 00:00 [accepted] PHST- 2019/05/06 06:00 [pubmed] PHST- 2019/12/04 06:00 [medline] PHST- 2019/05/04 06:00 [entrez] AID - S0378-5173(19)30348-5 [pii] AID - 10.1016/j.ijpharm.2019.04.077 [doi] PST - ppublish SO - Int J Pharm. 2019 Jun 30;565:199-208. doi: 10.1016/j.ijpharm.2019.04.077. Epub 2019 Apr 30.