Polyester-idarubicin nanoparticles and a polymer-photosensitizer complex as potential drug formulations for cell-mediated drug delivery

• Published in: International journal of pharmaceutics 2014-10, Vol.474 (1-2), p.70-79
• Main Authors: Blaudszun, André-R., Lian, Qiong, Schnabel, Melanie, Loretz, Brigitta, Steinfeld, Ute, Lee, Hyeck-H., Wenz, Gerhard, Lehr, Claus-M., Schneider, Marc, Philippi, Anja
• Format: Article
• Language: English
• Subjects: Cells, Cultured; Chemistry, Pharmaceutical; Drug Delivery Systems; Gold shell nanoparticle; Humans; Idarubicin - chemistry; Molecular Structure; Nanoparticles - chemistry; Particle Size; Photosensitizer; Photosensitizing Agents - chemistry; Polymeric nanoparticle; Polymers - chemical synthesis; Polymers - chemistry; Surface Properties; T lymphocyte; T-Lymphocytes - chemistry; Targeted drug delivery
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2014.07.048

[Display omitted] Cell-mediated transport of therapeutics has emerged as promising alternative to classical drug delivery approaches. To preserve viability and functions of carrier cells, encapsulation of active drugs in protective nanoparticles or the use of inducible therapeutics has been proposed. Here, we compared the effects of novel polymeric formulations of an active and a stimulus-sensitive anti-cancer drug on human T lymphocytes to identify suitable drug preparations for cell-mediated drug delivery. For the first approach, the chemotherapeutic agent idarubicin (IDA) was encapsulated in poly(lactic-co-glycolic-acid) (PLGA) and newly developed maleate-polyester (MPE) nanoparticles. PLGA- and MPE-encapsulated IDA was efficiently internalized by ex vivo activated human T lymphocytes; however, both encapsulations could not prevent premature T cell death resulting from IDA-uptake. In contrast, loading with a poly(styrene sulfonate) (PSS)-complex of the light-sensitive pharmaceutical 5,10,15,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP) did not affect T cell viability if upon loading the cells were kept in the dark. The photosensitizer was transferred from loaded T lymphocytes to co-cultivated carcinoma cells, and induced cancer cell death if co-cultures were exposed to light. Inducible drugs, such as photosensitizers, thus, may help to overcome the limitations of encapsulated active drugs and open up new perspectives for the use of cells as drug transporters in cancer therapy.