Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain

Abstract

1,4-Dihydropyridines (DHPs) are the most important class of L-type calcium channel blockers that are employed for the treatment of cardiovascular diseases, particularly hypertension. Various modifications on this scaffold lead to the discovery of new DHPs blocking different types of calcium channels. Among them, the T-type calcium channel has recently attracted great interest due to its role in chronic pain conditions. In this study, we selected three newly synthesized DHPs (HM8, HM10 and MD20) with different selectivity profiles to the T-type calcium channel and formulated them in micellar solutions and micellar-in-gel matrices to be tested for potential topical use in the treatment of neuropathic pain. To prevent the well-known sensitivity to light of the DHPs, the studied compounds were entrapped in colloidal aggregates obtained by using edible Pluronic® surfactants and adding α-tocopherol as an antioxidant. All the prepared formulations were exposed to stressing light, according to international rules. Along with the degradation experiments, the concentrations of the parent compounds and by-products were calculated by multivariate curve resolution—alternating least squares (MCR-ALS) applied to the spectral data. The defined formulations proved suitable as light-stable matrices for the DHP compounds, showing an increase in stability for HM8 and MD20 and an almost complete photoprotection for HM10, compared to ethanol solutions and standard gel formulations.

Polymeric micelles as a strategy to enhance the phototoxic efficacy of phenazine photosensitizers

“…Note that 0.5% wt/vol of F108 was not enough to solubilize NRBr although the copolymer concentration is still higher than its CMC. 34,37,38 The same results can be observed in relation to the concentration of the PS loaded in the different micellar systems (Figure 2C,D). These figures show that the entrapment increased linearly as a function of the concentration of NR or NRBr used in the preparation of the nanophotosensitizers.…”

“…For these reasons, the micelles prepared with 5% (wt/vol) of polymers showed higher EE (%) than the systems prepared with 0.5% (wt/vol) for both P123 and F108. Note that 0.5% wt/vol of F108 was not enough to solubilize NRBr although the copolymer concentration is still higher than its CMC 34,37,38 …”

Multivariate Approaches in Quantitative Structure–Property Relationships Study for the Photostability Assessment of 1,4-Dihydropyridine Derivatives

“…The sequence of the UV spectra during light irradiation was recorded for each 1,4-DHP solution (20.0 µg mL −1 ). According to our previous studies [12][13][14], a gradual decrease in the maximum peak in the zone 350-370 nm, which is a typical signal of the 1,4-DHP structure, and a contemporary increase in a new peak in the zone 260-280 nm, which is characteristic of the pyridinic structure, were observed for all the compounds. As an example, Figure 1A shows the sequence of the spectra recorded for DA9 and HM16.…”

“…After their introduction into the market, miscellaneous structural modifications on 1,4-DHPs resulted in efficient inhibitors of various calcium channels or in different pharmacological activities. Indeed, chemical modifications on the ester moiety of condensed 1,4-DHPs yielded up to thirty times more selectivity on T-type calcium channels compared to L-type, thus making them potentially useful in pain therapies [ 12 , 13 ].…”

Aggregation-induced emission (AIE) from poly(1,4-dihydropyridine)s synthesized by Hantzsch polymerization and their specific detection of Fe2+ ions

“…22,23 In recent years, this reaction has been introduced into the field of polymer chemistry and has gained wide interest. [24][25][26][27][28][29] In theory, when a diamine and dialdehyde are selected as the components in a Hantzsch reaction system, Hantzsch polymerization can take place, and the resulting poly(1,4-dihydropyridine) derivatives (PDPEs) can be prepared. In our experiments, we have selected five common diamines (ethylenediamine, butanediamine, hexamethylenediamine, 1,8-diaminooctane, and 1,10-diaminodecane) and two dialdehydes (aromatic terephthalaldehyde and aliphatic glutaraldehyde) as the difunctional components.…”