Phenolic compounds are a large, heterogeneous group of secondary metabolites found in various plants and herbal substances. From the perspective of dermatology, the most important benefits for human health are their pharmacological effects on oxidation processes, inflammation, vascular pathology, immune response, precancerous and oncological lesions or formations, and microbial growth. Because the nature of phenolic compounds is designed to fit the phytochemical needs of plants and not the biopharmaceutical requirements for a specific route of delivery (dermal or other), their utilization in cutaneous formulations sets challenges to drug development. These are encountered often due to insufficient water solubility, high molecular weight and low permeation and/or high reactivity (inherent for the set of representatives) and subsequent chemical/photochemical instability and ionizability. The inclusion of phenolic phytochemicals in lipid-based nanocarriers (such as nanoemulsions, liposomes and solid lipid nanoparticles) is so far recognized as a strategic physico-chemical approach to improve their in situ stability and introduction to the skin barriers, with a view to enhance bioavailability and therapeutic potency. This current review is focused on recent advances and achievements in this area.

This study aimed to develop a semisolid vehicle for topical delivery of nanoencapsulated St. John’s wort (SJW) extract, rich in hyperforin (HP), and explore its wound-healing potential. Four nanostructured lipid carriers (NLCs) were obtained: blank and HP-rich SJW extract-loaded (HP-NLC). They comprised glyceryl behenate (GB) as a solid lipid, almond oil (AO), or borage oil (BO) representing the liquid lipid, along with polyoxyethylene (20) sorbitan monooleate (PSMO) and sorbitan monooleate (SMO) as surfactants. The dispersions demonstrated anisometric nanoscale particles with acceptable size distribution and disrupted crystalline structure, providing entrapment capacity higher than 70%. The carrier exhibiting preferable characteristics (HP-NLC2) was gelled with Poloxamer 407 (PM407) to serve as the hydrophilic phase of a bigel, to which the combination of BO and sorbitan monostearate (SMS) organogel was added. The eight prepared bigels with different proportions (blank and nanodispersion-loaded) were characterized rheologically and texturally to investigate the impact of the hydrogel-to-oleogel ratio. The therapeutic potential of the superior formulation (HP-NLC-BG2) was evaluated in vivo on Wistar male rats through the tensile strength test on a primary-closed incised wound. Compared with a commercial herbal semisolid and a control group, the highest tear resistance (7.764 ± 0.13 N) was achieved by HP-NLC-BG2, proving its outstanding wound-healing effect.

St. John’s wort is a medicinal herb well-known for its antidepressant, anti-inflammatory, antimycotic, and wound-healing properties. Hyperforin, the major phloroglucinol derivative, has been implicated as one of the main contributors to these therapeutic effects. Because of its high reactivity, this phytochemical can cause various adverse effects, such as allergic reactions, dizziness, dry mouth, and fatigue. To predict critical parameters of hyperforin’s possible behavior after oral administration, in silico methods were applied. The pharmacokinetic profile, bioactivity, and toxicity of the phytochemical were analyzed by applying Molinspiration cheminformatics, SwissADME, PreADME/Tox, and OECD QSAR Toolbox software. The results showed adequate absorption, a high affinity for plasma proteins, and a prolonged renal excretion of the acylphloroglucinol. The high metabolic activity, a reason for potential cyto- and genotoxicity, and the predicted carcinogenicity and mutagenicity of hyperforin, necessitate further in vitro and in vivo tests.

Knowing the superior biochemical defense mechanisms of sessile organisms, it is not hard to believe the cure for any human sickness might be hidden in nature—we “just” have to identify it and make it safely available in the right dose to our organs and cells that are in need. For decades, green tea catechins (GTCs) have been a case in point. Because of their low redox potential and favorable positioning of hydroxyl groups, these flavonoid representatives (namely, catechin—C, epicatechin—EC, epicatechin gallate—ECG, epigallocatechin—EGC, epigallocatechin gallate—EGCG) are among the most potent plant-derived (and not only) antioxidants. The proven anti-inflammatory, neuroprotective, antimicrobial, and anticarcinogenic properties of these phytochemicals further contribute to their favorable pharmacological profile. Doubtlessly, GTCs hold the potential to “cope” with the majority of today‘s socially significant diseases, yet their mass use in clinical practice is still limited. Several factors related to the compounds’ membrane penetrability, chemical stability, and solubility overall determine their low bioavailability. Moreover, the antioxidant-to-pro-oxidant transitioning behavior of GTCs is highly conditional and, to a certain degree, unpredictable. The nanoparticulate delivery systems represent a logical approach to overcoming one or more of these therapeutic challenges. This review particularly focuses on the lipid-based nanotechnologies known to be a leading choice when it comes to drug permeation enhancement and not drug release modification nor drug stabilization solely. It is our goal to present the privileges of encapsulating green tea catechins in either vesicular or particulate lipid carriers with respect to the increasingly popular trends of advanced phytotherapy and functional nutrition.

In this time of COVID-19 pandemic, the strategies for prevention of the infection are a primary concern. Looking more globally on the subject and acknowledging the high degree of misuse of protective face masks from the population, we focused this review on alternative pharmaceutical developments eligible for self-defense against respiratory infections. In particular, the attention herein is directed to the nasal and oromucosal formulations intended to boost the local immunity, neutralize or mechanically “trap” the pathogens at the site of entry (nose or mouth). The current work presents a critical review of the contemporary methods of immune- and chemoprophylaxis and their suitability and applicability in topical mucosal dosage forms for SARS-CoV-2 prophylaxis.

Background/Objectives: This study aims to gain insights into the antimicrobial and antiherpetic activity of hyperforin-rich Hypericum perforatum L. (HP) extract using nanostructured lipid carriers (NLCs) as delivery platforms. Methods: 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 Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 10145, Klebsiella pneumoniae ATCC 10031, and Candida albicans ATCC 10231. The anti-herpesvirus (HSV-1) potential was evaluated concerning antiviral and virucidal activity and impact on viral adsorption. Results: The borage oil-based extract-loaded nanodispersion (HP-NLC2) exhibited pronounced microbicidal activity against S. aureus (MBC 6.3 mg/mL), K. pneumoniae (MBC 97.7 µg/mL), and C. albicans (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 E. coli, P. aeruginosa, the HSV-1 extracellular virions, or viral adhesion. Conclusions: 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.