Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 10;13(4):527.
doi: 10.3390/pharmaceutics13040527.

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

Giuseppina Ioele  1 , Rita Muzzalupo  1 , Miyase Gözde Gündüz  2 , Michele De Luca  1 , Elisabetta Mazzotta  1 , Fedora Grande  1 , Maria Antonietta Occhiuzzi  1 , Antonio Garofalo  1 , Gaetano Ragno  1
Affiliations

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

Giuseppina Ioele et al. Pharmaceutics. .

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.

Keywords: Pluronic® surfactants; T-type calcium channel blockers; drug photostability; multivariate curve resolution; α-tocopherol.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of HM8, HM10 and MD20.
Figure 2
Figure 2
Size distribution of HM10 loaded in F127 micelles, in triplicate.
Figure 3
Figure 3
UV spectra recorded along the photodegradation test on the ethanol solutions of HM8, HM10 and MD20.
Figure 4
Figure 4
Spectra (A) and concentration profiles (B) for HM8, HM10 and MD20, and their photoproducts.
Figure 5
Figure 5
Photodegradation of HM8, HM10 and MD20 in ethanol, surfactant solutions and gel formulations. ES, ethanol solution; T, α-tocopherol.
Figure 6
Figure 6
Comparison of the photodegradation profiles of HM8, HM10 and MD20 in ethanol and gel formulations.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Zamponi G.W., Striessnig J., Koschak A., Dolphin A.C. The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential. Pharmacol. Rev. 2015;67:821–870. doi: 10.1124/pr.114.009654. - DOI - PMC - PubMed
    1. Simms B.A., Zamponi G.W. Neuronal Voltage-Gated Calcium Channels: Structure, Function, and Dysfunction. Neuron. 2014;82:24–45. doi: 10.1016/j.neuron.2014.03.016. - DOI - PubMed
    1. Snutch T.P., Zamponi G.W. Recent advances in the development of T-type calcium channel blockers for pain intervention. Br. J. Pharmacol. 2018;175:2375–2383. doi: 10.1111/bph.13906. - DOI - PMC - PubMed
    1. Bladen C., Gadotti V.M., Gündüz M.G., Berger N.D., Şimşek R., Şafak C., Zamponi G.W. 1,4-Dihydropyridine derivatives with T-type calcium channel blocking activity attenuate inflammatory and neuropathic pain. Pflug. Arch. Eur. J. Physiol. 2015;467:1237–1247. doi: 10.1007/s00424-014-1566-3. - DOI - PubMed
    1. Gadotti V.M., Bladen C., Zhang F.X., Chen L., Gündüz M.G., Şimşek R., Şafak C., Zamponi G.W. Analgesic effect of a broad-spectrum dihydropyridine inhibitor of voltage-gated calcium channels. Pflüger’s Arch. Gesammte Physiol. Menschen Tiere. 2015;467:2485–2493. doi: 10.1007/s00424-015-1725-1. - DOI - PubMed

LinkOut - more resources