Synthesis, hydrolysis, and skin retention of amino acid esters of α-tocopherol

Marra, Fabio; Ostacolo, Carmine; Laneri, Sonia; Bernardi, Antonietta; Sacchi, Antonia; Padula, Cristina; Nicoli, Sara

doi:10.1002/jps.21608

Cited by 9 publications

(5 citation statements)

References 23 publications

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“…This finding may be related to the impact of ethanol on micelle size and compactness and thus on esterase accessibility to TPGS. An alternative hypothesis could be linked to a direct inhibitory effect of ethanol (present at approximately 50 μL/mL concentration) on enzyme activity even if literature data indicate that the presence of 10% organic solvent (methanol) did not have any effect on esterase activity . Finally, the stability of vitamin E in the aqueous solution at 37 °C for 48 h was not evaluated and could, at least in principle, affect the release profiles reported in Figure .…”

Section: Resultsmentioning

confidence: 99%

“…An alternative hypothesis could be linked to a direct inhibitory effect of ethanol (present at approximately 50 μL/mL concentration) on enzyme activity even if literature data indicate that the presence of 10% organic solvent (methanol) did not have any effect on esterase activity. 71 Finally, the stability of vitamin E in the aqueous solution at 37 °C for 48 h was not evaluated and could, at least in principle, affect the release profiles reported in Figure 7. Nevertheless, the presence of polymeric surfactants should contribute to increase its stability.…”

Section: Molecular Pharmaceuticsmentioning

confidence: 99%

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Poloxamer 407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery

et al. 2018

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Cyclosporine is an immunosuppressant agent approved for the treatment of dry eye disease and used off-label for other ocular pathologies. Its formulation and ocular bioavailability present a real challenge due to the large molecular weight (1.2 kDa), high lipophilicity, and low water solubility. The aim of the work was to develop an aqueous micellar formulation for an efficient cyclosporine delivery to the ocular tissues, using a water-soluble derivative of vitamin E (TPGS: d-α-tocopheryl polyethylene glycol 1000 succinate) and poloxamer 407 (Pluronic ®F127) as excipients. The mixed micelles were characterized in terms of particle size, zeta potential, rheology, and stability upon dilution and freeze-drying. Additionally, the enzymatic-triggered release of vitamin E and vitamin E succinate from TPGS was investigated in vitro in the presence of esterase. Compared to the commercially available ophthalmic formulation, the poloxamer 407:TPGS 1:1 molar ratio micellar formulation significantly improved cyclosporine solubility, which increased proportionally to surfactant concentration reaching 0.4% (w/v) for 20 mM surfactant total concentration. Cyclosporine-loaded mixed micelles efficiently retained the drug once diluted in simulated lachrymal fluid and, in the presence of a 20 mM surfactant concentration, were stable upon freeze-drying. The drug-loaded mixed micelles were applied ex vivo on porcine cornea and compared to Ikervis®. Drug accumulation in the cornea resulted proportional to drug concentration (6.4 ± 1.9, 17.6 ± 5.4, and 26.9 ± 7.4 μg/g, after 3 h for 1, 2.5, and 4 mg/mL cyclosporine concentration respectively). The formulation containing cyclosporine 4 mg/mL (20 mM surfactant) was also evaluated on the sclera, with a view to targeting the posterior segment. The results demonstrated the capability of mixed micelles to diffuse into the sclera and sustain cyclosporine delivery (28 ± 7, 38 ± 10, 57 ± 9, 145 ± 27 μg/cm cyclosporine accumulated after 3, 6, 24, and 48 h respectively). Reservoir effect experiments demonstrated that the drug accumulated in the sclera can be slowly released into the underlying tissues. Finally, all the formulations developed in this work successfully passed the HET-CAM assay for the evaluation of ocular irritability.

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Section: Resultsmentioning

confidence: 99%

Section: Molecular Pharmaceuticsmentioning

confidence: 99%

Poloxamer 407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery

et al. 2018

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“…All experiments were repeated in triplicate. Preliminary experiments were performed using acetyl salicylic acid as reference compounds to evaluate the hydrolytic activity of mice serum samples …”

Section: Methodsmentioning

confidence: 99%

Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo Analgesic Activity

et al. 2018

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TRPM8 has been implicated in nociception and pain and is currently regarded as an attractive target for the pharmacological treatment of neuropathic pain syndromes. A series of analogues of N, N'-dibenzyl tryptamine 1, a potent TRPM8 antagonist, was prepared and screened using a fluorescence-based in vitro assay based on menthol-evoked calcium influx in TRPM8 stably transfected HEK293 cells. The tryptophan derivative 14 was identified as a potent (IC 0.2 ± 0.2 nM) and selective TRPM8 antagonist. In vivo, 14 showed significant target coverage in both an icilin-induced WDS (at 1-30 mg/kg s.c.) and oxaliplatin-induced cold allodynia (at 0.1-1 μg s.c.) mice models. Molecular modeling studies identified the putative binding mode of these antagonists, suggesting that they could influence an interaction network between the S1-4 transmembrane segments and the TRP domains of the channel subunits. The tryptophan moiety provides a new pharmacophoric scaffold for the design of highly potent modulators of TRPM8-mediated pain.

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“…Vitamin E esters still retain free radical scavenging capacity. Free radicals generated by UV-induced melatonin interacted with vitamin E and vitamin E ester derivatives, including vitamin E acetate, vitamin E linoleic acid ester, and vitamin E succinate, and their free radical scavenging ability was tested [16,17]. The results showed that vitamin E linoleic acid ester had the inhibitory effect of 25.6% at the mass concentration of 1%, while vitamin E succinic acid ester had the inhibitory effect of 37.6% at the mass concentration of 0.1% [17].…”

Section: Main Function Of Ve Ester Derivativesmentioning

confidence: 99%

Research Progress in Enzymatic Synthesis of Vitamin E Ester Derivatives

Dai

Liu

2021

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Vitamin E is easily oxidized by light, air, oxidizing agents and heat, limiting its application in many ways. Compared to vitamin E, vitamin E ester derivatives exhibit improved stability and a stronger antioxidant capacity, and even gain new biological functions. In recent years, enzymatic synthesis of vitamin E ester derivatives has received increasing attention due to its environmental friendliness, high catalytic efficiency, and inherent selectivity. This paper reviews the related progress of lipase-mediated preparation of vitamin E ester derivatives. The function of different vitamin E ester derivatives, and the main factors influencing the enzymatic acylation process, including enzyme species, acyl donor and acceptor, reaction media and water activity, are summarized in this paper. Finally, the perspective of lipase-catalyzed synthesis of vitamin E ester derivatives is also discussed.

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Synthesis, hydrolysis, and skin retention of amino acid esters of α-tocopherol

Cited by 9 publications

References 23 publications

Poloxamer 407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery

Poloxamer 407/TPGS Mixed Micelles as Promising Carriers for Cyclosporine Ocular Delivery

Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo Analgesic Activity

Research Progress in Enzymatic Synthesis of Vitamin E Ester Derivatives

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