Pharmacological evaluation of a new nanoformulation in the erectile tissue of rabbits and humans

Iury A Paz; Pedro M Silva Filho; Alexandre S Leitão Junior; Tatiana Oliveira Pessoa; Renata O Santiago; Nádia Osório de Oliveira; Elisane Longhinotti; Eduardo H S Sousa; Luiz G F Lopes; Claudia F Santos; Manassés C Fonteles; Nilberto R F Nascimento

doi:10.1016/j.ejphar.2024.177071

Pharmacological evaluation of a new nanoformulation in the erectile tissue of rabbits and humans

Eur J Pharmacol. 2024 Oct 22:985:177071. doi: 10.1016/j.ejphar.2024.177071. Online ahead of print.

Affiliations

¹ Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, State University of Ceará, 1700. Dr Silas Munguba Av., 60455-900, Fortaleza, Ceará, Brazil; Group of Bioinorganic, Department of Organic and Inorganic Chemistry, Federal University of Ceará, PO Box 6021, 60440-900, Fortaleza, Ceará, Brazil.
² Department of Analytical and Physical Chemistry, Federal University of Ceará, PO Box 6021, Fortaleza, 60440-900, Fortaleza, Ceará, Brazil; Academic Department of Chemistry and Biology, Technologic Federal University of Paraná, 81280-340, Curitiba, Paraná, Brazil.
³ Departament of Urology, Federal University of Ceará, 1290 Pastor Samuel Munguba St., Fortaleza - CE, 60430-372, Fortaleza, Ceará, Brazil.
⁴ Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, State University of Ceará, 1700. Dr Silas Munguba Av., 60455-900, Fortaleza, Ceará, Brazil.
⁵ Group of Bioinorganic, Department of Organic and Inorganic Chemistry, Federal University of Ceará, PO Box 6021, 60440-900, Fortaleza, Ceará, Brazil.
⁶ Department of Physiology and Pharmacology, Superior Institute of Biomedical Sciences, State University of Ceará, 1700. Dr Silas Munguba Av., 60455-900, Fortaleza, Ceará, Brazil. Electronic address: nilberto.nascimento@uece.br.

PMID: 39447860
DOI: 10.1016/j.ejphar.2024.177071

Abstract

The failure of achieving a penile erection for satisfactory sexual intercourse is known as erectile dysfunction (ED). The primary mediator for penile erection is nitric oxide (NO). ED is often associated with endothelial/nitrergic dysfunction characterized by a reduction of the bioavailability of NO. Phosphodiesterase-5 inhibitors (PDE-5Is) clinical efficacy in the treatment of ED depends on the integrity of the NO-sGC-PKG pathway. In the present study, we probed the effect of sodium nitroprusside incorporated into mesoporous silica nanoparticles (MPSi-NP), which traps cyanide and slowly releases NO. MPSi-NP induced a maximal relaxation of 92.8 ± 5.2% in rabbit corpora cavernosa (RbCC), blunted by a soluble guanylate cyclase (sGC) inhibitor and blockers of calcium-dependent potassium channels. MPSi-NP abolished spontaneous contractions of human corpora cavernosa (HCC) strips. In addition, MPSi-NP induced maximal relaxation of phenylephrine precontracted HCC by 118.6 ± 3.6%, and in comparison, tadalafil induced a maximal relaxation of HCC by 98.3 ± 1.2%. Similarly, the sGC inhibitor blocked the MPSi-NP relaxation. MPSi-NP potentiated the relaxation induced by tadalafil. MPSi-NP increased cGMP levels in HCC strips by 2.6-fold and increased by 3.5-fold the phosphorylation level of the VASP protein, which is a downstream target to PKG. MPSi-NP effectively relaxes RbCC and HCC by activating the sGC-PKG pathway and potentiates the tadalafil response. MPSi-NP could be helpful in conditions where nitric oxide availability is decreased. A topical gel formulation of MPSi-NP could be used as a rescue therapy to treat true non-responders of PDE5Is drugs.