Evaluation of polyvinylpyrrolidone and block copolymer micelle encapsulation of serine chlorin e6 and chlorin e4 on their reactivity towards albumin and transferrin and their cell uptake.

Gjuroski, Ilche; Girousi, Eleftheria; Meyer, Christoph; Hertig, Damian; Stojkov, Darko; Fux, Michaela; Schnidrig, Nicolas; Bucher, Jan; Pfister, Sara; Sauser, Luca; Simon, Hans-Uwe; Vermathen, Peter; Furrer, Julien; Vermathen, Martina (2019). Evaluation of polyvinylpyrrolidone and block copolymer micelle encapsulation of serine chlorin e6 and chlorin e4 on their reactivity towards albumin and transferrin and their cell uptake. Journal of controlled release, 316, pp. 150-167. Elsevier 10.1016/j.jconrel.2019.10.010

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Encapsulation of porphyrinic photosensitizers (PSs) into polymeric carriers plays an important role in enhancing their efficiency as drugs in photodynamic therapy (PDT). Porphyrin aggregation and low solubility as well as the preservation of the advantageous photophysical properties pose a challenge on the design of efficient PS-carrier systems. Block copolymer micelles (BCMs) and polyvinylpyrrolidone (PVP) are promising drug delivery vehicles for physical entrapment of PSs. BCMs exhibit enhanced dynamics as compared to the less flexible PVP network. In the current work the question is addressed how these different dynamics affect PS encapsulation, release from the carrier, reaction with serum proteins, and cellular uptake. The porphyrinic compounds serine-amide of chlorin e6 (SerCE) and chlorin e4 (CE4) were used as model PSs with different lipophilicity and aggregation properties. 1H NMR and fluorescence spectroscopy were applied to study their interactions with PVP and BCMs consisting of Kolliphor P188 (KP). Both chlorins were well encapsulated by the carriers and had improved photophysical properties. Compared to SerCE, the more lipophilic CE4 exhibited stronger hydrophobic interactions with the BCM core, stabilizing the system and preventing exchange with the surrounding medium as was shown by NMR NOESY and DOSY experiments. PVP and BCMs protected the encapsulated chlorins against interaction with human transferrin (Tf). However, SerCE and CE4 were released from BCMs in favor of binding to human serum albumin (HSA) while PVP prevented interaction with HSA. Fluorescence spectroscopic studies revealed that HSA binds to the surface of PVP forming a protein corona. PVP and BCMs reduced cellular uptake of the chlorins. However, encapsulation into BCMs resulted in more efficient cell internalization for CE4 than for SerCE. HSA significantly lowered both, free and carrier-mediated cell uptake for CE4 and SerCE. In conclusion, PVP appears as the more universal delivery system covering a broad range of host molecules with respect to polarity, whereas BCMs require a higher drug-carrier compatibility. Poorly soluble hydrophobic PSs benefit stronger from BCM-type carriers due to enhanced bioavailability through disaggregation and solubilization allowing for more efficient cell uptake. In addition, increased PS-carrier hydrophobic interactions have a stabilizing effect. For more hydrophilic PSs, the main advantage of polymeric carriers like PVP or poloxamer micelles lies in their protection during the transport through the bloodstream. HSA binding plays an important role for drug release and cell uptake in carrier-mediated delivery to the target tissue.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic, Interventional and Paediatric Radiology > DCR Magnetic Resonance Spectroscopy and Methodology (AMSM)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Abt. Magnetresonanz-Spektroskopie und Methodologie, AMSM
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > School of Dental Medicine > Department of Orthodontics
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Gjuroski, Ilche, Girousi, Eleftheria, Hertig, Damian, Stojkov, Darko, Fux, Michaela, Bucher, Jan Rudolf, Simon, Hans-Uwe, Vermathen, Peter, Furrer, Julien, Vermathen, Martina


600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry








Renate Imhof-Etter

Date Deposited:

28 Nov 2019 14:15

Last Modified:

05 Dec 2022 15:32

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Block copolymer micelles Chlorin Drug delivery PVP Photodynamic therapy Serum proteins





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