Nose to brain delivery of dapoxetine-loaded PLGA nanoparticle for treatment of premature ejaculation distress in normal and diabetic rats with in silico targeting brain FOX and serotonin proteins
Abstract
Psychological and emotional sexual conditions in men include premature ejaculation. Premature Ejaculation (PE) has 4%–66% worldwide effects on self-esteem, relationships, and quality of life. Poor sexual confidence, anxiety, and sadness may worsen the issue. For this disease, dapoxetine HCl (DH) is used. In normal and streptozotocin (STZ)-induced diabetic rats, DH-loaded poly (lactic-co-glycolic acid) PLGA NP intranasal (IN) therapy was compared to standard lidocaine for DH release, entrapment efficiency, behavioural analysis, histopathological and immunohistochemistry expression, as neuroprotection inspection and proto-oncogene c-Fos (FOS) protein sequence expression. Also, in silico brain serotonin and FOS protein analyses were performed. Double-emulsion-solvent evaporation produced DH-loaded PLGA NP for IN quick-acting PE. Safe, controlled release, and effectiveness were investigated in PE rats using DH-PLGA NP. The brain’s FOS protein expression, mount, intromission, post-ejaculatory, and Ejaculation frequencies were estimated. Optimized spherical NPs were 174 nm in size, − 69.45 mV zeta potential, 98.04% entrapment efficiency, and 78.61% release after 8 h. The brain’s ejaculation centre’s rapid-acting DH prolongs intra-ejaculation, lowers FOS protein density, and normalizes hippocampus neurons. Histology and immunohistochemistry confirmed behavioural results of lower FOS protein expression and delayed ejaculation. Docking revealed that the DH ligand binds more strongly…
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