Medical-Grade Honey Outperforms Conventional Treatments for Healing Cold Sores—A Clinical Study

Cold sores are nasolabial blisters caused by herpes simplex virus (HSV) infections. Novel therapies demonstrating simultaneously antiviral activity and improved wound healing are warranted. The aim of this study was to investigate the efficacy of medical-grade honey (MGH) for treating HSV-induced cold sores. A crossover trial was performed in patients with recurrent cold sores (n = 29). The majority (65.6%) of these patients experience four or more episodes per year, thus forming a valid self-control group. In this study, patients applied an MGH-based formulation (L-Mesitran Soft) on their cold sore at the onset of symptoms (62.1%) or appearing of blister (37.9%) and compared it to their conventional treatments. After complete healing, patients filled in a questionnaire evaluating healing, pain, and itching. The average absolute healing time was 72.4% slower with conventional treatment (10.0 days) compared to MGH (5.8 days). After MGH treatment, 86.2% of all patients experienced faster objective healing (6.9% similar and 6.9% slower) and the subjective healing score was higher in 79.3% of the patients (20.7% similar). If the patients normally experience pain and itching during their cold sores, these levels were lower with MGH therapy compared to conventional treatment in 72.7% and 71.4% of the patients, respectively. Moreover, 100% of the patients prefer MGH treatment over conventional treatment and will use it again on future cold sores. MGH is a promising alternative treatment for cold sores, likely by combining both increased antiviral and wound healing activities while alleviating pain and itching.

Antiviral Potential of Naphthoquinones Derivatives Encapsulated within Liposomes

HSV infections, both type 1 and type 2, are among the most widespread viral diseases affecting people of all ages. Their symptoms could be mild, with cold sores up to 10 days of infection, blindness and encephalitis caused by HSV-1 affecting immunocompetent and immunosuppressed individuals. The severe effects derive from co-evolution with the host, resulting in immune evasion mechanisms, including latency and growing resistance to acyclovir and derivatives. An efficient alternative to controlling the spreading of HSV mutations is the exploitation of new drugs, and the possibility of enhancing their delivery through the encapsulation of drugs into nanoparticles, such as liposomes. In this work, liposomes were loaded with a series of 2-aminomethyl- 3-hydroxy-1,4-naphthoquinones derivatives with n-butyl (compound 1), benzyl (compound 2) and nitrobenzene (compound 3) substituents in the primary amine of naphthoquinone. They were previously identified to have significant inhibitory activity against HSV-1. All of the aminomethylnaphthoquinones derivatives encapsulated in the phosphatidylcholine liposomes were able to control the early and late phases of HSV-1 replication, especially those substituted with the benzyl (compound 2) and nitrobenzene (compound 3), which yields selective index values that are almost nine times more efficient than acyclovir. The growing interest of the industry in topical administration against HSV supports our choice of liposome as a drug carrier of aminomethylnaphthoquinones derivatives for formulations of in vivo pre-clinical assays.

Berberine in Human Oncogenic Herpesvirus Infections and Their Linked Cancers

Human herpesviruses are known to induce a broad spectrum of diseases, ranging from common cold sores to cancer, and infections with some types of these viruses, known as human oncogenic herpesviruses (HOHVs), can cause cancer. Challenges with viral latency, recurrent infections, and drug resistance have generated the need for finding new drugs with the ability to overcome these barriers. Berberine (BBR), a naturally occurring alkaloid, is known for its multiple biological activities, including antiviral and anticancer effects. This paper comprehensively compiles all studies that have featured anti-HOHV properties of BBR along with promising preventive effects against the associated cancers. The mechanisms and pathways induced by BBR via targeting the herpesvirus life cycle and the pathogenesis of the linked malignancies are reviewed. Approaches to enhance the therapeutic efficacy of BBR and its use in clinical practice as an anti-herpesvirus drug are also discussed.

The Pharmacists’ and pharmacy technicians’ scopes of practice in the management of minor ailments at community pharmacies in Indonesia: a cross-sectional study

Background: Managing minor ailments in community pharmacy is an evolving pharmacy service in developing countries. Defined scopes of practice for pharmacy staff are essential for the safe management of minor ailments. Limited research exists regarding the perceptions of Indonesian pharmacists’ and pharmacy technicians’ scopes of practice in providing minor ailments management services. Objective: To evaluate pharmacists’ and pharmacy technicians’ understanding of their scopes of practice, perceived competency and factors influencing the delivery of minor ailments services in Indonesian community pharmacies. Methods: Cross-sectional surveys were conducted during January-February 2020 of pharmacists and pharmacy technicians attending seminars conducted by relevant Indonesian Associations in Central Java, Indonesia. Percentage of common responses (PCR) described similarity of perceived scopes of practice for pharmacists and pharmacy technicians. Univariate and multivariate analyses identified associations of scopes of practice with pharmacy characteristics. Results: A total of 185 pharmacists and 142 pharmacy technicians participated. Pharmacy technicians performed minor ailment consultations, however, if considered beyond their scope of practice, they referred the patient to the pharmacist (T=120/142, 84.5%). Vaginal thrush, bacterial conjunctivitis, gastro-oesophageal reflux disease, and acute pain were minor ailments perceived only within a pharmacist’s scope (PCR above 60%). Of 34 minor ailments, 11 showed PCR values between 40-60% overlapping pharmacists and pharmacy technicians perceived scopes of practice (allergy/rash, back pain, cold sores, dermatitis, diarrhoea, eczema, hayfever, haemorrhoids, rheumatism, sore throat, and superficial wounds). Back pain, cold sores, dermatitis, and sore throat associated pharmacists’ scope of practice with years of practice experience (p-value<0.05). Pharmacy technicians perceived their scopes of practice to be wider than perceived by pharmacists. Conclusions: Discordance between pharmacists’ and pharmacy technicians’ perceived scopes of minor ailments management highlights the need for clearly defined scopes of practice for each professional group. Each professional group must practise within their competence to ensure safe pharmacy practices.

Transdermal Film Loaded with Garlic Oil-Acyclovir Nanoemulsion to Overcome Barriers for Its Use in Alleviating Cold Sore Conditions

The exponentially mounting cases of herpes simplex virus infection or cold sores have become a serious global concern. Acyclovir (ACV) and garlic oil (GO)-loaded lipid nanocarrier could be a promising therapeutic approach in alleviating cold sores, as well as limiting the biopharmaceutical constraints associated with ACV absorption and therapeutic efficacy. Therefore, the objective of the current research study was to formulate an ACV-GO self-nanoemulsifying drug delivery system (ACV-GO-SNEDDS) as transdermal films. The prepared SNEDDS was optimized using an experimental mixture design. The optimized ACV-GO SNEDDS was loaded in transdermal film and was evaluated for ex vivo skin permeation and in vivo pharmacokinetic prospects. An optimized ACV-GO SNEDDs formulation constituted of 10.4% (w/w) of GO, 64.8% (w/w) of surfactant mixture (Tween 20®-Span 20®); 24.8%(w/w) of co-surfactant (Propylene glycol®), and 200mg of ACV, respectively, were prepared and characterized for particle size (Y). The observed globule size of the optimized ACV-GO SNEDDS is 170 ± 13.45 nm. The results of stability studies indicated that the stability index of optimized ACV-GO-SNEDDS was more than 92 ± 3%. This optimized ACV-GO SNEDDS was loaded in hydroxypropyl cellulose transdermal film. The outcome of the ex vivo skin permeation study demonstrated a 2.3-fold augmented permeation of ACV from the optimized ACV-GO SNEDDS HPC transdermal film in comparison to the raw ACV transdermal film. There was a 3-fold increase in the relative bioavailability of the optimized ACV-GO SNEDDS transdermal film compared to the raw ACV-HPC film. The study findings confirmed that the ACV-GO SNEDDS transdermal film exhibited excellent potential to enhance the bioavailability of ACV.

Pseudoboehmite as a drug delivery system for acyclovir

Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of low permeability across the gastrointestinal membrane. Based on experiments using nanoparticles of pseudoboehmite as a drug delivery system in vitro assays it was concluded that pseudoboehmite could be used for acyclovir release. We report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles. Pseudoboehmite was characterized by several techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content in the plasma of Wistar rats after 4 h administration. The toxicity of pseudoboehmite was also evaluated using the Caco-2 cell line (ATCC).

Vaccine Development for Herpes Simplex Viruses: A Commentary of Special Issue Editors

Herpes simplex virus type 1 and 2 (HSV1 and HSV2) are global, widespread human pathogens transmitted by direct contact that cause lifelong, recurrent asymptomatic and painful symptomatic clinical illnesses (cold sores, keratitis, blepharitis, meningitis, encephalitis, genital infections), overt disease and severe sequelae in neonatal and immune-compromised patients, and increased risk of cervical cancer and other sexually transmitted infections, including HIV [...]