5-aminolevulinic acid-incorporated nanoparticles of methoxy poly(ethylene glycol)-chitosan copolymer for photodynamic therapy

Abstract

Purpose: The aim of this study was to make 5-aminolevulinic acid (5-ALA)-incorporated nanoparticles using methoxy polyethylene glycol/chitosan (PEG-Chito) copolymer for application in photodynamic therapy for colon cancer cells. Methods: 5-ALA-incorporated (PEG-Chito-5-ALA) nanoparticles were prepared by ion complex formation between 5-ALA and chitosan. Protoporphyrin IX accumulation in the tumor cells and phototoxicity induced by PEG-Chito-5-ALA nanoparticles were assessed using CT26 cells in vitro.Results: PEG-Chito-5-ALA nanoparticles have spherical shapes with sizes diameters 200 nm. More specifically, microscopic observation revealed a core-shell structure of PEG-Chito-5-ALA nanoparticles.1 H NMR spectra showed that 5-ALA was incorporated in the core of the nanoparticles. In the absence of light irradiation, all components such as 5-ALA, empty nanoparticles, and PEG-Chito-5-ALA nanoparticles did not affect the viability of cells. However, 5-ALA or PEG-Chito-5-ALA nanoparticles induced tumor cell death under light irradiation, and the viability of tumor cells was dose-dependently decreased according to the increase in irradiation time. In particular, PEG-Chito-5-ALA nanoparticles induced increased phototoxicity and higher protoporphyrin IX accumulation into the tumor cells than did 5-ALA alone. Furthermore, PEG-Chito-5-ALA nanoparticles accelerated apoptosis/necrosis of tumor cells, compared to 5-ALA alone. Conclusion: PEG-Chito-5-ALA nanoparticles showed superior delivery capacity of 5-ALA and phototoxicity against tumor cells. These results show that PEG-Chito-5-ALA nanoparticles are promising candidates for photodynamic therapy of colon cancer cells.

Tunable phosphatase-sensitive stable prodrugs of 5-aminolevulinic acid for tumor fluorescence photodetection

“…The major reasoning is that increased lipophilicity potentially improves the passage through biological membranes thus increasing intracellular substrate concentration for heme biosynthesis. Recently, substantial efforts have also been directed towards nanocarriers loaded [20][21][22][23][24] or conjugated [25][26][27][28] with 5-ALA. These approaches tackle some of the pharmacokinetic and specificity drawbacks of 5-ALA but have so far failed to produce a clinical candidate for the improved delivery of 5-ALA mostly due to high 5-ALA loading and delivery required for this type of FPD or PDT.…”

Chemically triggered release of 5-aminolevulinic acid from liposomes

“…7 In these PDT applications, the PpIX is exploited as a photosensitizer, whereby red light irradiation of the diseased tissue that has been treated with 5-ALA produces a localized burst of cytotoxic reactive oxygen species. 8, 9 …”

Development of chitosan nanoparticles as drug delivery system for a prototype capsid inhibitor

“…Various nanotechnologies have been employed for improving oral drug delivery (Preshita P et al, 2012).Natural polymer chitosan and their derivatives have been widely used for the development of self-assembled nanoparticles which could increase the drug oral bioavailability (Cho et al, 2012;Chung et al, 2013;Lee et al, 2011;Nogueira et al, 2013). Due to their good muco adhesive character, they are used as pharmaceutical carriers for sustained drug release (Hirano, 1996).…”