Temperature-sensitive and Chemically Cross-linked Poly (N isopropylacrylamide)/Photosensitizer Hydrogels for Photodynamic Therapy of

سال انتشار: 1397
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 314

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شناسه ملی سند علمی:

NHSMED01_062

تاریخ نمایه سازی: 18 آذر 1398

چکیده مقاله:

Background and Objective:Photodynamic therapy (PDT) relies on the activation of a photosensitizer (PS) using visible or near IR light to generate reactive oxygen species, such as singlet oxygen, as cytotoxic agents.1 Porphyrins feature prominently among the clinically approved PDT drugs and typical examples of porphyrin-based drugs include Photofrin® (porfimer sodium), Visudyne® (verteporfin), and Foscan® (temoporfin).2 A recurring problem is the intrinsically low water-solubility of many porphyrinoid PSs and their tendency to aggregate in polar solvents and biological media. Aggregation results in quenching of the excited states, thus lowering the singlet oxygen yields, and impacts the ability of a PS to reach the target tissue limiting its clinical use. In order to overcome these limitations and to obviate side effects different strategies to improve the pharmacological profile of PSs have been developed.3 hydrogels have attracted attention as a rather simple and facile means to solubilize and deliver drugs.4Materials and Method: The PpIX-PNIPAM hydrogels were synthesized using the in situ dispersion polymerization method in a mixture of water and dimethylformamide (DMF, as organic solvent for dissolution of protoporphyrin IX in the reaction mixture). In a typical procedure, NIPAM (2.65 mmol, 300 mg), N, N-methylenebisacrylamide (MBA) (0.1 mmol, 16 mg) and PVP (300 mg) were dissolved in 6 mL of deionized water and PpIX (2% w/w, 6 mg, 3% w/w, 9 mg or 4% w/w, 12 mg) was dissolved in DMF, with both solutions then mixed in a Schlenk tube under nitrogen gas. The solution was stirred at 350 rpm and heated to 70 °C for 40 min under continuous purging with nitrogen atmosphere. The initiator, potassium persulfate (0.076 mmol, 200 mg), dissolved in 1.0 mL of deionized water, was added to the mixture to start polymerization.Finding: poly(N-isopropylacrylamide)-PSs (PpIX, Pba and PpIX-DME) hydrogels have been successfully synthesized with different percentages of photosensitizers as a copolymer in the hydrogel structure. Incorporation of the PS functionalities was easily achieved using the dispersion polymerization method by mixing organic and aqueous solvents. Significantly, spectroscopic data prove that the porphyrin units are incorporated in a ‘monomeric’ manner, without aggregation and thus capable of significant singlet oxygen production. In the case of the PpIX-PNIPAM hydrogel, the absorption spectrum has a sharp Soret band at 405 nm, clearly indicating the absence of aggregation, which is further confirmed by its strong fluorescence emission.Conclusion: All PS-hydrogel preparations showed that using the PS as a chemical cross-linker (copolymer) during hydrogel formation is an effective means to: a) solubilize the photosensitizer for use in aqueous media, b) to prepare formulations where the PS is effectively monomeric, i.e., photoactive and capable of significant 1O2 production, c) can be used to modulate the LCST to physiologically relevant parameters, and d) can yield highly effective light-activated PDT drug candidates.

کلیدواژه ها:

Protoporphyrin IX – Hydrogels – Photodynamic therapy – Poly (N-isopropylacrylamide) – Photosensitizer

نویسندگان

Simin Belali

Department of Chemistry, Faculty of Science, Arak University, Arak ۳۸۱۵۶-۸-۸۳۴۹, Iran.

Ali Reza Karimi

Department of Chemistry, Faculty of Science, Arak University, Arak ۳۸۱۵۶-۸-۸۳۴۹, Iran.