The chimera of TPGS and Nanoscale Lipid Carriers as Lymphatic Drug Delivery Vehicles to Fight Metastatic Cancers.

The lymphatic system (LS) plays a crucial role in fluid balance, transportation of macromolecules, and immune response. Moreover, LS is a channel for microbial invasion and cancer metastasis. Particularly, solid tumors, including lung, breast, melanoma, and prostate cancers, are metastasized across highways of LS. Subsequently, the fabrication of chimeric lymphatic drug delivery systems (LDDS) is a promising strategy to fight cancer metastasis and control microbial pandemics. In this regard, LDDS, in terms of PEG-nanoscaled lipid carriers, elicited a revolution during the COVID-19 pandemic as cargoes for mRNA vaccines. The drug delivered by the lymphatic pathway escapes first-pass metabolism and enhances the drug's bioavailability. Ample approaches, including synthesis of prodrugs, trigging of chylomicron biosynthesis, and fabrication of nanocarriers, facilitate lymphatic drug delivery. Specifically, nanoscales lipid cargoes have the propensity to lymphatic trafficking. Interestingly, TPGS-engineered nanoscale lipid cargoes enhance lymphatic trafficking, increase tissue permeation, and, specifically, uptake. Moreover, they overcome biological barriers, control biodistribution, and enhance organelles localization. Most anticancer agents are non-specific, have low bioavailability, and induced drug resistance. Therefore, TPGS-engineered nanoscale lipid chimeras improve the therapeutic impact of anticancer agents. This review highlights lymphatic cancer metastasis, nanoscales lipid cargoes as LDDS, and their influence on lymphatic trafficking, besides the methods of LDD studies.

HL-100 Outcomes of Patients With Hodgkin Lymphoma During a Period of Drug Shortage in Lebanon: A Single-Center Experience

Context: Hodgkin lymphoma (HL) represents two-thirds of all lymphomas diagnosed in Lebanon. Due to the COVID-19 pandemic and the unprecedented financial crisis, shortages of oncology drugs are now common in Lebanon. The shortage of conventional agents has created remarkable challenges for both HL patients and health care providers. We lack studies that document the outcome of HL in Lebanon during this period. Objective: To determine the outcome of HL patients treated in Lebanon during the period of drug shortages. Design, Setting, and Participants: This retrospective study included 52 HL patients diagnosed between October 2019 and December 2021 at Hôtel Dieu de France Hospital in Lebanon. Patients had classical or nodular lymphocyte–predominant subtypes. Main Outcome Measures: The treatment patterns, frequency of incomplete protocols, missing agents, and response to first-line treatment were analyzed. Results: A total of 52 patients were reviewed with a median age of 35 years (range, 15–85 years);52% were male. In this study, 65% of patients had B symptoms at diagnosis, 70% had no comorbidities, 64% had an advanced stage, 60% had bulky disease, and 90% had low- to intermediate-risk disease according to the International Prognostic Score. The nodular sclerosing subtype was the most common histological subtype (77%). The ABVD regimen was offered to 85% of patients and radiotherapy was offered to 10%. Eleven patients (22%) did not receive the full treatment per protocol due to drug shortage: 8 patients (15%), 2 patients (4%), and 1 patient (2%) had missing bleomycin, dacarbazine, and vinblastine, respectively. Of these patients, 6 (54%) received treatment without the missing agent, 4 (36%) imported the medication from an external source at their own expense, and 1 (9%) was switched to another protocol. Among 11 patients who did not receive proper therapy, the rates of complete response, partial response, stable disease, and progressive disease were 70%, 15%, 5%, and 10%, respectively. Conclusions: In this single-institution study from Lebanon, the outcomes of patients with HL treated during an unprecedented crisis and drugs shortage were comparable to those of previous reports. This emphasizes the resilience of the Lebanese population and adaptability despite hard conditions.

Pharmacological features, health benefits and clinical implications of honokiol.

Honokiol (HNK) is a natural polyphenolic compound extracted from the bark and leaves of Magnolia grandiflora. It has been traditionally used as a medicinal compound to treat inflammatory diseases. HNK possesses numerous health benefits with a minimal level of toxicity. It can cross the blood-brain barrier and blood-cerebrospinal fluid, thus having significant bioavailability in the neurological tissues. HNK is a promising bioactive compound possesses neuroprotective, antimicrobial, anti-tumorigenic, anti-spasmodic, antidepressant, analgesic, and antithrombotic features . HNK can prevent the growth of several cancer types and haematological malignancies. Recent studies suggested its role in COVID-19 therapy. It binds effectively with several molecular targets, including apoptotic factors, chemokines, transcription factors, cell surface adhesion molecules, and kinases. HNK has excellent pharmacological features and a wide range of chemotherapeutic effects, and thus, researchers have increased interest in improving the therapeutic implications of HNK to the clinic as a novel agent. This review focused on the therapeutic implications of HNK, highlighting clinical and pharmacological features and the underlying mechanism of action.Communicated by Ramaswamy H. Sarma.

Triazoles and Their Derivatives: Chemistry, Synthesis, and Therapeutic Applications.

Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. Structurally, there are two types of five-membered triazoles: 1,2,3-triazole and 1,2,4-triazole. Due to the structural characteristics, both 1,2,3- and 1,2,4-triazoles are able to accommodate a broad range of substituents (electrophiles and nucleophiles) around the core structures and pave the way for the construction of diverse novel bioactive molecules. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities. These are also important in organocatalysis, agrochemicals, and materials science. Thus, they have a broad range of therapeutic applications with ever-widening future scope across scientific disciplines. However, adverse events such as hepatotoxicity and hormonal problems lead to a careful revision of the azole family to obtain higher efficacy with minimum side effects. This review focuses on the structural features, synthesis, and notable therapeutic applications of triazoles and related compounds.

Multidrug Resistance (MDR): A Widespread Phenomenon in Pharmacological Therapies.

Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. Multidrug resistance may be also related to antimicrobial drugs, and is known to be one of the most serious global public health threats of this century. Indeed, this phenomenon has increased both mortality and morbidity as a consequence of treatment failures and its incidence in healthcare costs. The large amounts of antibiotics used in human therapies, as well as for farm animals and even for fishes in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. It is not negligible that the ongoing COVID-19 pandemic may further contribute to antimicrobial resistance. In this paper, multidrug resistance and antimicrobial resistance are underlined, focusing on the therapeutic options to overcome these obstacles in drug treatments. Lastly, some recent studies on nanodrug delivery systems have been reviewed since they may represent a significant approach for overcoming resistance.

Recent Advances in Biomedical, Therapeutic and Pharmaceutical Applications of Microbial Surfactants.

The spread of antimicrobial-resistant pathogens typically existing in biofilm formation and the recent COVID-19 pandemic, although unrelated phenomena, have demonstrated the urgent need for methods to combat such increasing threats. New avenues of research for natural molecules with desirable properties to alleviate this situation have, therefore, been expanding. Biosurfactants comprise a group of unique and varied amphiphilic molecules of microbial origin capable of interacting with lipidic membranes/components of microorganisms and altering their physicochemical properties. These features have encouraged closer investigations of these microbial metabolites as new pharmaceutics with potential applications in clinical, hygiene and therapeutic fields. Mounting evidence has indicated that biosurfactants have antimicrobial, antibiofilm, antiviral, immunomodulatory and antiproliferative activities that are exploitable in new anticancer treatments and wound healing applications. Some biosurfactants have already been approved for use in clinical, food and environmental fields, while others are currently under investigation and development as antimicrobials or adjuvants to antibiotics for microbial suppression and biofilm eradication strategies. Moreover, due to the COVID-19 pandemic, biosurfactants are now being explored as an alternative to current products or procedures for effective cleaning and handwash formulations, antiviral plastic and fabric surface coating agents for shields and masks. In addition, biosurfactants have shown promise as drug delivery systems and in the medicinal relief of symptoms associated with SARS-CoV-2 acute respiratory distress syndrome.

The Complex Management of Atrial Fibrillation and Cancer in the COVID-19 Era: Drug Interactions, Thromboembolic Risk, and Proarrhythmia.

PURPOSE OF REVIEW: Cardiotoxicity by anticancer agents has emerged as a multifaceted issue and is expected to affect both mortality and morbidity. This review summarizes clinical challenges in the management of oncological patients requiring anticoagulants for atrial fibrillation (AF) also considering the current outbreak of the COVID-19 (coronavirus disease 2019) pandemic, since this infection can add challenges to the management of both conditions. Specifically, the aims are manyfold: (1) describe the evolving use of direct oral anticoagulants (DOACs) in AF patients with cancer; (2) critically appraise the risk of clinically important drug-drug interactions (DDIs) between DOACs and oral targeted anticancer agents; (3) address expected DDIs between DOACs and candidate anti-COVID drugs, with implications on management of the underlying thrombotic risk; and (4) characterize the proarrhythmic liability in cardio-oncology in the setting of COVID-19, focusing on QT prolongation. RECENT FINDINGS: AF in cardio-oncology poses diagnostic and management challenges, also due to the number of anticancer drugs recently associated with AF onset/worsening. Oral targeted drugs can potentially interact with DOACs, with increased bleeding risk mainly due to pharmacokinetic DDIs. Moreover, the vast majority of oral anticancer agents cause QT prolongation with direct and indirect mechanisms, potentially resulting in the occurrence of torsade de pointes, especially in susceptible patients with COVID-19 receiving additional drugs with QT liability. Oncologists and cardiologists must be aware of the increased bleeding risk and arrhythmic susceptibility of patients with AF and cancer due to DDIs. High-risk individuals with COVID-19 should be prioritized to target preventive strategies, including optimal antithrombotic management, medication review, and stringent monitoring.