Phthalocyanines are excellent photosensitizers for photodynamic therapy as they have strong absorbance in the near infra-red region which is most relevant for in vivo activation in deeper tissular regions. However, most phthalocyanines present two major challenges, ie, a strong tendency to aggregate and low water-solubility, limiting their effective usage clinically. In the present study, we evaluated the potential enhancement capability of glycerol substitution on the photodynamic properties of zinc (II) phthalocyanines (ZnPc). Three glycerol substituted ZnPc, 1–3, (tetra peripherally, tetra non-peripherally and mono iodinated tri non-peripherally respectively) were evaluated in terms of their spectroscopic properties, rate of singlet oxygen generation, partition coefficient (log P), intracellular uptake, photo-induced cytotoxicity and vascular occlusion efficiency. Tetrasulfonated ZnPc (ZnPcS4) was included as a reference compound. Here, we showed that 1–3 exhibited 10–100 nm red-shifted absorption peaks with higher molar absorptivity, and at least two-fold greater singlet oxygen generation rates compared to ZnPcS4. Meanwhile, phthalocyanines 1 and 2 showed more hydrophilic log P values than 3 consistent with the number of glycerol attachments but 3 was most readily taken up by cells compared to the rest. Both phthalocyanines 2 and 3 exhibited potent phototoxicity against MCF-7, HCT-116 and HSC-2 cancer cell-lines with IC50 ranging 2.8–3.2 µM and 0.04–0.06 µM respectively, while 1 and ZnPcS4 (up to 100 µM) failed to yield determinable IC50 values. In terms of vascular occlusion efficiency, phthalocyanine 3 showed better effects than 2 by causing total occlusion of vessels with diameter <70 µm of the chorioallantoic membrane. Meanwhile, no detectable vascular occlusion was observed for ZnPcS4 with treatment under similar experimental conditions. These findings provide evidence that glycerol substitution, in particular in structures 2 and 3, is able to improve the photodynamic properties of ZnPc.
BackgroundCough on emergence has been reported as a common adverse reaction with sugammadex reversal. We investigated if staggering the dose of sugammadex will reduce emergence cough in a single-center, randomized, double-blinded study.MethodsA hundred and twenty ASA 1–3 adults were randomly reversed with 1 mg/kg sugammadex prior to extubation followed by another 1 mg/kg immediately after extubation (staggered group), single dose of 2 mg/kg sugammadex (single bolus group) or neostigmine 0.02 mg/kg with glycopyrrolate (neostigmine group).ResultsWe found 70% of patients (n = 28) reversed with single boluses of sugammadex had Grade 3 emergence cough compared to 12.5% (n = 5) in the staggered sugammadex group and 17.5% (n = 7) in the neostigmine group (p < 0.001). Besides cough, emergence agitation also appeared highest in the single bolus sugammadex group (n = 14, 35%, p = 0.005). On the other hand, staggering sugammadex lowered risks of developing severe cough (RR 0.2, p < 0.001) and agitation (RR 0.43, p = 0.010) on emergence in addition to cough (RR 0.25, p = 0.039) and early sore throat (RR 0.70, p = 0.036) in the post-anesthetic care unit. The risks for severe emergence cough (RR 0.86, p = 0.762), severe cough in the post-anesthetic care unit (RR 1.0, p = 1.000) and sore throat (RR 1.17, p = 0.502) were also not different between the staggered sugammadex group and control given neostigmine. In terms of timing, there was no delay in time taken from discontinuing anesthetic agents to reversal and extubation if sugammadex was staggered (emergence time 6.0 ± 3.2 s, p = 0.625 and reversal time 6.5 ± 3.5, p = 0.809).ConclusionsStaggering the dose of sugammadex for reversal will effectively decrease common emergence and early postoperative complications.Trial registrationANZCTR Number ACTRN12616000116426. Retrospectively registered on 2nd February 2016.
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