Antimicrobial and Antiherpetic Properties of Nanoencapsulated Hypericum perforatum Extract

<b>Background/Objectives:</b> This study aims to gain insights into the antimicrobial and antiherpetic activity of hyperforin-rich <i>Hypericum perforatum</i> L. (HP) extract using nanostructured lipid carriers (NLCs) as delivery platforms. <b>Methods</b>: Two established NLC specimens, comprising glyceryl behenate and almond oil or borage oil, and their extract-loaded counterparts (HP-NLCs) were utilized. Their minimal bactericidal/fungicidal concentrations (MBC; MFC) were investigated against <i>Escherichia coli</i> ATCC 25922, <i>Staphylococcus aureus</i> ATCC 25923, <i>Pseudomonas aeruginosa</i> ATCC 10145, <i>Klebsiella pneumoniae</i> ATCC 10031, and <i>Candida albicans</i> ATCC 10231. The anti-herpesvirus (HSV-1) potential was evaluated concerning antiviral and virucidal activity and impact on viral adsorption. <b>Results</b>: The borage oil-based extract-loaded nanodispersion (HP-NLC2) exhibited pronounced microbicidal activity against <i>S. aureus</i> (MBC 6.3 mg/mL), <i>K. pneumoniae</i> (MBC 97.7 µg/mL), and <i>C. albicans</i> (MFC < 48.8 µg/mL), unlike the almond oil-containing sample (HP-NLC1), which showed only weak inhibition of the fungal growth. HP-NLC2 was found to be less cytotoxic and to suppress HSV-1 replication slightly more than HP-NLC1, but generally, the effects were weak. Neither the empty lipid nanoparticles nor the HP extract-loaded carriers expressed activity against <i>E. coli</i>, <i>P. aeruginosa</i>, the HSV-1 extracellular virions, or viral adhesion. <b>Conclusions</b>: It could be concluded that both HP-NLC samples revealed only minor antiherpetic potential of the hyperforin-rich extract, but HP-NLC2 demonstrated significant antibacterial and antimycotic activity. Therefore, the latter was featured as a more convenient HP-carrier system for nano-designed dermal pharmaceutical formulations. Such a thorough investigation of hyperforin-determined anti-HSV-1 effects and antibacterial and antimycotic properties, being the first of its kind, contributes to the fundamental knowledge of HP and reveals new perspectives for the utilization, limitations, and therapeutic designation of its non-polar components.