Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques

Abstract

Phthalocyanines are ideal candidates as photosensitizersfor photodynamictherapy (PDT) of cancer due to their favorable chemical and photophysicalproperties. However, their tendency to form aggregates in water reducesPDT efficacy and poses challenges in obtaining efficient forms ofphthalocyanines for therapeutic applications. In the current work,polyvinylpyrrolidone (PVP) and micellar formulations were comparedfor encapsulating and monomerizing a water-soluble zinc phthalocyaninebearing four non-peripheral triethylene glycol chains (Pc1). H-1 NMR spectroscopy combined with UV-vis absorptionand fluorescence spectroscopy revealed that Pc1 existsas a mixture of regioisomers in monomeric form in dimethyl sulfoxidebut forms dimers in an aqueous buffer. PVP, polyethylene glycol castoroil (Kolliphor RH40), and three different triblock copolymers withvarying proportions of polyethylene and polypropylene glycol units(termed P188, P84, and F127) were tested as micellar carriers for Pc1. H-1 NMR chemical shift analysis, diffusion-orderedspectroscopy, and 2D nuclear Overhauser enhancement spectroscopy wasapplied to monitor the encapsulation and localization of Pc1 at the polymer interface. Kolliphor RH40 and F127 micelles exhibitedthe highest affinity for encapsulating Pc1 in the micellarcore and resulted in intense Pc1 fluorescence emissionas well as efficient singlet oxygen formation along with PVP. Amongthe triblock copolymers, efficiency in binding and dimer dissolutiondecreased in the order F127 > P84 > P188. PVP was a strong binderfor Pc1. However, Pc1 molecules are rathersurface-attached and exist as monomer and dimer mixtures. The resultsdemonstrate that NMR combined with optical spectroscopy offer powerfultools to assess parameters like drug binding, localization sites,and dynamic properties that play key roles in achieving high host-guestcompatibility. With the corresponding adjustments, polymeric micellescan offer simple and easily accessible drug delivery systems optimizingphthalocyanines' properties as efficient photosensitizers.