Evaluation of Eudragit® Retard Polymers for the Microencapsulation of Alpha-Lipoic Acid.

BACKGROUND: Microencapsulation of natural antioxidants in polymeric systems represents a possible strategy for improving the oral bioavailability of compounds that are otherwise poorly soluble. OBJECTIVE: α-lipoic acid (ALA) was microencapsulated with polymethacrylate polymers (blends at various ratios of Eudragit® RS100 and RL100 resins). METHOD: Microspheres were produced by solvent displacement of an ethanol cosolution of ALA and polymers; the microsuspensions were then freeze-dried, using trehalose as a cryoprotector. Microspheres were characterized in the solid state for micromeritic properties and drug loading, as well as by infrared spectroscopy, powder X-ray diffractometry and differential scanning calorimetry. The antioxidant activity of free and encapsulated ALA was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. RESULTS: In vitro release studies, performed in simulated gastric (pH 1.2) and intestinal fluid (pH 6.8), showed that, depending on polymer composition and drug-to-polymer ratio, ALA release can be slowed down, compared to the dissolution pattern of the free drug. Solid-state characterization confirmed the chemical stability of ALA in the microspheres, suggesting that ALA did not develop strong interactions with the polymer and was present in an amorphous or a disordered-crystalline state within the polymer network. As indicated by the DPPH assay, the microencapsulation of ALA in Eudragit® Retard matrices did not alter its antioxidant activity. CONCLUSION: ALA was effectively encapsulated in Eudragit® Retard matrices, showing a chemical stability up to 6 months at room conditions and at 40°C. Moreover, since the drug maintained its antioxidant activity in vitro, the potential application of these microparticulate systems for oral administration would deserve further studies.

Comparative evaluation of different co-antioxidants on the photochemical- and functional-stability of epigallocatechin-3-gallate in topical creams exposed to simulated sunlight.

The catechin (-)-epigallocatechin-3-gallate (EGCG) exhibits high antioxidant activity and it has been reported to provide protection of the skin against damage induced by solar UV radiation. However, EGCG is highly unstable under sunlight. The present study aimed to compare the effectiveness of the co-antioxidant agents vitamin E, butylated hydroxytoluene, vitamin C and a-lipoic acid for their potential to protect the catechin from photochemical degradation. Model creams (oil-in-water emulsions) containing EGCG (1%, w/w) alone or combined with equimolar concentrations of co-antioxidant were exposed to a solar simulator at an irradiance corresponding to natural sunlight. Photodegradation was evaluated by HPLC-UV and HPLC-ESI-MS/MS. Addition of the co-antioxidants vitamin C and a-lipoic acid to the formulation significantly reduced the light-induced decomposition of EGCG from 76.9 ± 4.6% to 20.4 ± 2.7% and 12.6 ± 1.6%, respectively. Conversely, butylated hydroxytoluene had no effect (EGCG loss, 78.1 ± 4.6%) and vitamin E enhanced the EGCG photolysis to 84.5 ± 3.4%. The functional stability of the catechin in the creams exposed to the solar simulator was also evaluated by measuring the in vitro antioxidant activity. Following irradiation, the reduction of the EGCG formulation antioxidant power was lower (21.8%) than the extent of degradation (76.9%), suggesting the formation of photoproducts with antioxidant properties. The influence of the examined co-antioxidants on the functional stability of the catechin under simulated sunlight paralleled that measured for the EGCG photodecomposition, a-lipoic acid exerting the greatest stabilising effect (antioxidant activity decrease, 1.4%). These results demonstrated that a-lipoic acid is an effective co-antioxidant agent for the stabilization of EGCG in dermatological products for skin photoprotection.

The effect of biothiol on UV irradiated alpha-lipoic acid.

alpha-Lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA) are well known as strong antioxidants. LA has the characteristic distorted five membered 1,2-dithiolane ring, which is quite vulnerable to UV irradiation. The UV induced decomposition of LA and the effect of the following addition of biothiols to the photoirradiated solution of LA were investigated by UV-vis spectrometry and (1)H NMR spectral analysis. The mechanism of UV irradiated LA decomposition was proposed based on the results obtained from NMR and GPC measurements.

The photochemistry of lipoic acid: photoionization and observation of a triplet excited state of a disulfide.

Under short-wavelength UV irradiation, lipoic acid (LipSS) and its reduced form, dihydrolipoic acid (DHLA), undergo photoionization processes through a bi- or monophotonic pathway. After ionization, the LipSS radical cation (LipSS*+) and radical anion (LipSS*-) are generated. LipSS*- can be converted to equimolar amounts of LipSS and DHLA through second-order decay. Triplet acetone can be quenched by LipSS and DHLA with a rate close to the diffusion-controlled limit. The mechanism was further confirmed by continuous irradiation experiments. When LipSS is directly irradiated with UVA light, the first excited triplet state of LipSS is observed, with a lifetime tau=75 ns. Characteristic reactions include triplet energy transfer to oxygen and beta-carotene and addition to isoprene. The lifetime of triplet LipSS is also shortened by addition of water and methanol.

Photoinduced interactions between oxidized and reduced lipoic acid and riboflavin (vitamin B2).

As a powerful natural antioxidant, lipoic acid (LipSS) and its reduced form dihydrolipoic acid (DHLA) exert significant antioxidant activities in vivo and in vitro by deactivation of reactive oxygen and nitrogen species (ROS and RNS). In this study the riboflavin (RF, vitamin B2) sensitized UVA and visible-light irradiation of LipSS and DHLA was studied employing continuous irradiation, fluorescence spectroscopy, and laser flash photolysis (LFP). Our results indicate that LipSS and DHLA quench both the singlet state (1RF*) and the triplet state (3RF*) of RF by electron transfer to produce the riboflavin semiquinone radical (RFH.) and the radical cation of LipSS and DHLA, respectively. The radical cation of DHLA is rapidly deprotonated twice to yield a reducing species, the radical anion of LipSS (LipSS.-). When D2O was used as solvent, it was confirmed that the reaction of LipSS with 3RF* consists of a simple electron-transfer step, while loss of hydrogen occurs in the case of DHLA oxidation. Due to the strong absorption of RFH. and the riboflavin ground state, the absorption of the radical cation and the radical anion of LipSS can not be observed directly by LFP. N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) and N,N,N',N'-tetramethyl benzidine (TMB) were added as probes to the system. In the case of LipSS, the addition resulted in the formation of the radical cation of TMPD or TMB by quenching of the LipSS radical cation. If DHLA is the reducing substrate, no formation of probe radical cation is observed. This confirms that LipSS.- is produced by riboflavin photosensitization, and that there is no oxidizing species produced after DHLA oxidization.

Interactions of lipoic acid radical cations with vitamins C and E analogue and hydroxycinnamic acid derivatives.

As a powerful natural antioxidant, lipoic acid exerts significant antioxidant activities in vivo and in vitro by deactivation of reactive oxygen and nitrogen species. In this study we present a novel synergistic interaction of lipoic acid with other endogenous or exogenous antioxidants. Antioxidants vitamins C and E analogue (Trolox C) and hydroxycinnamic acid derivatives were found to recycle lipoic acid by donating electrons to lipoic acid radical cations, thereby increasing the antioxidant capacity of lipoic acid in vivo and in vitro. The rate constant of the electron transfer is in the order 10(9)dm(3)mol(-1)s(-1), close to the diffusion-controlled limit, and transfer quantum yield is above 95%.