Light-responsive polymeric nanoparticles based on a novel nitropiperonal based polyester as drug delivery systems for photosensitizers in PDT.

Although nanoparticles (NPs) bear a great potential in tumour therapy, just a few nanosized drug delivery systems are commercially available. Besides their advantages like passive drug targeting and stable embedment of lipophilic active pharmaceutical ingredients, targeted drug release is a major challenge for a safe therapy. While drug release of commonly used materials depends on physiological factors, nanoparticles prepared by using stimuli responsive polymers offer a promising approach. External irradiation of light-sensitive nanoparticles enables local drug release, resulting in selective accumulation and consequently more effective treatment with less side effects. In this study light-responsive nanoparticles based on a new innovative light-responsive polyester (Nip-SLrPE) combined with poly(DL-lactide-co-glycolide) (PLGA) were prepared and examined for their physicochemical characteristics and light-triggered properties. As model drug the photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorine (mTHPC) was incorporated and light-depending drug release was investigated. Furthermore, cytotoxic potential of selected formulations for PDT and intracellular accumulation of mTHPC were evaluated. In conclusion, nanoparticles based on the new light-sensitive Nip-SLrPE showed auspicious light-responsive properties, resulting in promising results for a smart drug delivery system.

Light-Responsive Serinol-Based Polycarbonate and Polyester as Degradable Scaffolds.

Stimuli-responsive self-immolative aliphatic polycarbonates (APCs) and polyesters (APEs) have attractive advantages for biomedical and pharmaceutical applications. In the present work, polycondensation of o-nitrobenzyl-protected serinol was explored as a simple route to obtain light-responsive polycarbonate (LrPC) and polyester (LrPE). By exposure to UV light, these polymers decomposed rapidly and completely into oligomers and small molecules, as detected by size exclusion chromatography (SEC), UV/vis, and 1H nuclear magnetic resonance (NMR) spectroscopies. The degradation mechanism of serinol-based APC and APE was investigated with the help of the Boc-protected model APC and APE, showing that the APC underwent intramolecular cyclization, accompanied by intermolecular transcarbamation, and degraded into oxazolidinone and 2-aminopropanol terminated oligourethanes. Different from APC, the degradation process of serinol-based APE has been proven by electrospray ionization time-of-flight mass spectrometry (ESI-ToF-MS) to follow intramolecular cyclization of the functional amine group with the remote ester group, forming a ten-membered cyclic degradation compound. Further processing of the serinol-based polymers was performed by preparation of nanoparticles (NP). With light-responsive characteristics, a drug delivery system could be potentially obtained enabling a controllable drug release. Based on this strategy, a variety of self-immolative polymers responsive to different triggers can be prepared by polycondensation without the limit of ring-opening polymerization and will expand the family of biodegradable polymers.