Anti-Herpetic Activity of Callissia fragrans and Simmondsia chinensis Leaf Extracts In Vitro

The antiviral activity of Callissia fragrans and Simnondsia chinensis aquatic and ethanol leaf extracts, as well as purified fractions from these extracts was studied against herpetic viruses in vitro. Ethanol extract of C. fragrans effectively inhibited the infection of Vero cells by HSV-1, HSV-2 in vitro, while its aquatic extract inhibited only VZV. Although S. chinensis leaf extract strongly inhibited all studied viruses, the selectivity index of this extract was very low, due to its high toxicity. However, the majority of its fractions showed low toxicity and higher antiviral activity and therefore very high SI. Strong interactions between virus and extracts were found

Prodrugs for Improved Drug Delivery: Lessons Learned from Recently Developed and Marketed Products

Prodrugs are bioreversible, inactive drug derivatives, which have the ability to convert into a parent drug in the body. In the past, prodrugs were used as a last option; however, nowadays, prodrugs are considered already in the early stages of drug development. Optimal prodrug needs to have effective absorption, distribution, metabolism, and elimination (ADME) features to be chemically stable, to be selective towards the particular site in the body, and to have appropriate safety. Traditional prodrug approach aims to improve physicochemical/biopharmaceutical drug properties; modern prodrugs also include cellular and molecular parameters to accomplish desired drug effect and site-specificity. Here, we present recently investigated prodrugs, their pharmaceutical and clinical advantages, and challenges facing the overall prodrug development. Given examples illustrate that prodrugs can accomplish appropriate solubility, increase permeability, provide site-specific targeting (i.e., to organs, tissues, enzymes, or transporters), overcome rapid drug metabolism, decrease toxicity, or provide better patient compliance, all with the aim to provide optimal drug therapy and outcome. Overall, the prodrug approach is a powerful tool to decrease the time/costs of developing new drug entities and improve overall drug therapy

Modern Prodrug Design for Targeted Oral Drug Delivery

The molecular information that became available over the past two decades significantly influenced the field of drug design and delivery at large, and the prodrug approach in particular. While the traditional prodrug approach was aimed at altering various physiochemical parameters, e.g., lipophilicity and charge state, the modern approach to prodrug design considers molecular/cellular factors, e.g., membrane influx/efflux transporters and cellular protein expression and distribution. This novel targeted-prodrug approach is aimed to exploit carrier-mediated transport for enhanced intestinal permeability, as well as specific enzymes to promote activation of the prodrug and liberation of the free parent drug. The purpose of this article is to provide a concise overview of this modern prodrug approach, with useful successful examples for its utilization. In the past the prodrug approach used to be viewed as a last option strategy, after all other possible solutions were exhausted; nowadays this is no longer the case, and in fact, the prodrug approach should be considered already in the very earliest development stages. Indeed, the prodrug approach becomes more and more popular and successful. A mechanistic prodrug design that aims to allow intestinal permeability by specific transporters, as well as activation by specific enzymes, may greatly improve the prodrug efficiency, and allow for novel oral treatment options

The Fundamental Role of Lipids in Polymeric Nanoparticles: Dermal Delivery and Anti-Inflammatory Activity of Cannabidiol

This report presents a nanoparticulate platform for cannabidiol (CBD) for topical treatment of inflammatory conditions. We have previously shown that stabilizing lipids improve the encapsulation of CBD in ethyl cellulose nanoparticles. In this study, we examined CBD release, skin permeation, and the capability of lipid-stabilized nanoparticles (LSNs) to suppress the release of IL-6 and IL-8. The nanoparticles were stabilized with cetyl alcohol (CA), stearic acid (SA), lauric acid (LA), and an SA/LA eutectic combination (SALA). LSN size and concentration were measured and characterized by differential scanning calorimetry (DSC), in vitro release of loaded CBD, and skin permeability. IL-6 and IL-8 secretions from TNF-α-induced HaCaT cells were monitored following different LSN treatments. CBD released from the LSNs in dispersion at increasing concentrations of polysorbate 80 showed non-linear solubilization, which was explained by recurrent precipitation. A significant high release of CBD in a cell culture medium was shown from SALA-stabilized nanoparticles. Skin permeation was >30% lower from SA-stabilized nanoparticles compared to the other LSNs. Investigation of the CBD-loaded LSNs’ effect on the release of IL-6 and IL-8 from TNF-α-induced HaCaT cells showed that nanoparticles stabilized with CA, LA, or SALA were similarly effective in suppressing cytokine release. The applicability of the CBD-loaded LSNs to treat topical inflammatory conditions has been supported by their dermal permeation and release inhibition of pro-inflammatory cytokines

Cannabis as a Source of Approved Drugs: A New Look at an Old Problem

Cannabis plants have been used in medicine since ancient times. They are well known for their anti-diabetic, anti-inflammatory, neuroprotective, anti-cancer, anti-oxidative, anti-microbial, anti-viral, and anti-fungal activities. A growing body of evidence indicates that targeting the endocannabinoid system and various other receptors with cannabinoid compounds holds great promise for addressing multiple medical conditions. There are two distinct avenues in the development of cannabinoid-based drugs. The first involves creating treatments directly based on the components of the cannabis plant. The second involves a singular molecule strategy, in which specific phytocannabinoids or newly discovered cannabinoids with therapeutic promise are pinpointed and synthesized for future pharmaceutical development and validation. Although the therapeutic potential of cannabis is enormous, few cannabis-related approved drugs exist, and this avenue warrants further investigation. With this in mind, we review here the medicinal properties of cannabis, its phytochemicals, approved drugs of natural and synthetic origin, pitfalls on the way to the widespread clinical use of cannabis, and additional applications of cannabis-related products

Medicinal Properties of Anchusa strigosa and Its Active Compounds

Anchusa strigosa is a widespread weed in Greece, Syria, Turkey, Lebanon, Israel, Jordan, and Iran. The purpose of this study was to identify the phytochemicals of Anchusa strigose and estimate the pro-wound healing (pro-WH) and antimicrobial activities of its active compounds. An identification of volatile compounds was performed by GC/MS analysis; HPLC, LC-ESI-MS, and MALDI-TOF-MS were also applied. Our results demonstrate that two specific combinations of compounds from A. strigosa extract significantly enhanced WH (p < 0.001). Several flavonoids of the plant extract, including quercetin 3-O-rutinoside, kaempferol, kaempferol 3-O-β-rhamnopyranosyl(1→6)-β-glucopyranoside, and kaempferol 3-O-α-rhamnopyranosyl(1→6)-β-galactopyranoside, were effective against drug-resistant microorganisms. In addition, all the above-mentioned compounds had antibiofilm activity against Escherichia coli and Salmonella enteritidis

Effect of Bioactive Phytochemicals from Phlomis viscosa Poiret on Wound Healing

Phlomis viscosa Poiret is an evergreen shrub growing in Israel, Turkey, Lebanon, and Syria with acknowledged pro-wound healing (WH) properties. In this study, we evaluated the pro-WH potential of selected compounds found in this plant. Among the pro-WH compounds (identified by us) was a combination of three chemicals—diosmin, 1-octen-3-ol, and himachala-2,4-diene which enhanced WH significantly both in in vitro and in vivo models. The determined phytochemicals combination could be used for the treatment of chronic wounds. The effect of the extracts, diosmin, 1-octen-3-ol on the secretion of pro-inflammatory cytokines, IL-6 (A) and IL-8 (B) by human dermal fibroblasts was significant (p < 0.001). In addition, the beneficial effect of extracts of P. viscosa and its phytochemicals on WH was evidenced by inhibiting the growth of several WH delaying microorganisms